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Activated carbon (AC) and biochar (BC) are porous materials with large surface areas and widely used in environmental and industrial applications. In this study, different types of AC and BC samples were produced from Sargassum sp. by a chemical activation and pyrolysis process and compared to commercial activated carbon samples. All samples were characterized using various techniques to understand their structure and functionalities. The metal content of the samples was characterized by using an inductively coupled optical emission spectrometer (ICP-OES). A toxicity test was applied to investigate the effect of AC/BC on organisms, where Sinapis alba seed and Escherichia coli bacteria-based toxicity tests were used. The results revealed that the samples did not negatively affect these two organisms. Thus, it is safe to use them in various applications. Therefore, the samples were tested as fillers in polyurethane composites and, thus, polyurethane-AC/BC samples were prepared. The amounts of AC/BC mixed into the polyurethane formulation were 1%, 2%, and 3%. Mechanical and acoustic properties of these composites were analyzed, showing that by adding the AC/BC to the system an increase in the compression strength for all the samples was achieved. A similar effect of the AC/BC was noticed in the acoustic measurements, where adding AC/BC enhanced the sound adsorption coefficient (α) for all composite materials. [ABSTRACT FROM AUTHOR]

Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes. Three valve groups were tested: raw PSIS as a control and two calcified groups that were seeded with human valvular interstitial and endothelial cells (VICs/VECs) and cultivated in calcifying media. These two calcified groups were cultured in either static or bioreactor-induced oscillatory flow conditions. Hydrodynamic assessments showed metrics were below thresholds associated for even mild calcification. Young's modulus, however, was significantly higher in calcified valves when compared to raw PSIS, indicating the morphological changes to the tissue structure. Fluid–structure interaction (FSI) simulations agreed well with hydrodynamic results and, most notably, showed a significant increase in time-averaged wall shear stress (TAWSS) between raw and calcified groups. We conclude that tracking hemodynamics may be a viable biomarker for early-stage CAVD tracking. [ABSTRACT FROM AUTHOR]

Background: Gamma Knife Radiosurgery (GKRS), a specific type of Stereotactic Radiosurgery (SRS), has developed as a significant modality in the treatment of glioblastoma, particularly in conjunction with standard chemotherapy. The goal of this study is to evaluate the efficacy of combining GKRS with surgical resection and chemotherapy in enhancing therapeutic effects for glioblastoma patients aged 55 years and older. Methods: This prospective clinical study, conducted in accordance with the STROBE guidelines, involved 49 glioblastoma patients aged 55 years and older, treated between January 2013 and January 2023. Data were collected prospectively, and strict adherence to the STUPP protocol was maintained. Only patients who conformed to the STUPP protocol were included in the analysis. Due to concerns regarding the cognitive impairment associated with conventional radiotherapy, and at the patients' request, a radiosurgery plan was offered. Radiosurgery was administered for 4–8 weeks following surgical resection. Any patients who had not received previous radiotherapy received open surgical tumor removal, followed by GKRS along with adjuvant chemotherapy. Results: In this prospective clinical study of 49 glioblastoma patients aged 55 years and older, the average lifespan post-histopathological diagnosis was established at 22.3 months (95% CI: 12.0–28.0 months). The median time before disease progression was 14.3 months (95% CI: 13.0–29.7 months). The median duration until the first recurrence after treatment was 15.2 months, with documented cases varying between 4 and 33 months. The Gamma Knife Radiosurgery (GKRS) treatment involved a median marginal recommended dose of 12.5 Gy, targeting an average volume of 5.7 cm3 (range: 1.6–39 cm3). Local recurrence occurred in 21 patients, while distant recurrence was identified in 8 patients. Within the cohort, 34 patients were subjected to further therapeutic approaches, including reoperation, a second GKRS session, the administration of bevacizumab and irinotecan, and PCV chemotherapy. A cognitive function assessment revealed that the patients treated with GKRS experienced significantly less cognitive decline compared to the historical controls, who were treated with conventional radiotherapy. The median MMSE scores declined by 1.9 points over 12 months, and the median MoCA scores declined by 2.9 points. Conclusion: This study demonstrates that Gamma Knife Radiosurgery (GKRS), when integrated with surgical resection and adjuvant chemotherapy, offers a substantial benefit for glioblastoma patients aged 55 years and older. The data reveal that GKRS not only prolongs overall survival and progression-free survival but also significantly reduces cognitive decline compared to conventional radiotherapy. These findings underscore the efficacy and safety of GKRS, advocating for its incorporation into standard treatment protocols for older glioblastoma patients. The potential of GKRS to improve patient outcomes while preserving cognitive function is compelling and warrants further research to optimize and confirm its role in glioblastoma management. [ABSTRACT FROM AUTHOR]

As the issue of climate change becomes more prevalent, engineers have focused on developing lightweight Al alloys capable of increasing the power density of powertrains. The characterization of these alloys has been focused on mechanical properties and less on the fundamental response of microstructures to achieve these properties. Therefore, this study assesses the quality of the microstructure of two high-temperature Al alloys (A356 + 3.5RE and Al-8Ce-10Mg), comparing them to T6 A356. These alloys underwent thermal conditioning at 250 and 300 °C for 200 h. Time-of-flight neutron diffraction experiments were performed before and after conditioning. The phase evolution was quantified using Rietveld refinement. It was found that the Si phase grows significantly (13–24%) in T6 A356, A356 + 3.5RE, and T6 A356 + 3.5RE alloys, which is typically correlated with a reduction in mechanical properties. Subjecting the A356 3.5RE alloy to a T6 heat treatment stabilizes the orthorhombic Al4Ce3Si6 and monoclinic β-Al5FeSi phases, making them resistant to thermal conditioning. These two phases are known for enhancing mechanical properties. Additionally, the T6 treatment reduced the vol.% of the cubic Al20CeTi2 and hexagonal ᴨ-Al9FeSi3Mg5 phases by 13% and 23%, respectively. These phases have detrimental mechanical properties. The Al-8Ce-10Mg alloy cubic β-Al3Mg2 phase showed significant growth (82–101%) in response to conditioning, while the orthorhombic Al11Ce3 phase remained stable. The growth of the beta phase is known to decrease the mechanical properties of this alloy. These efforts give valuable insight into how these alloys will perform and evolve in demanding high-temperature environments. [ABSTRACT FROM AUTHOR]

The microstructure and mechanical properties of as-cast Al-10Ce-3Mg-xZn (x = 0, 1, 3, 5 wt.%) alloys were systematically investigated, with a focus on the effect of Zn on the Al11Ce3 reinforcing phase in the alloy. The results showed that the Al-10Ce-3Mg alloy consists of α-Al, a Chinese-script Al11Ce3 eutectic phase, and a massive Al11Ce3 primary phase. With the addition of Zn content, most of the Zn atoms are enriched in the Al11Ce3 phase to form the acicular-like Al2CeZn2 phase within the Al11Ce3 phase. Increasing the Zn content can increase the volume fraction of the Al11Ce3 phase. Compared to the alloy without Zn addition, the microhardness and elastic modulus of the Al2CeZn2-reinforced Al11Ce3 phase in the alloy with 5 wt.% Zn increased by 18.9% and 9.0%, respectively. Moreover, the room-temperature mechanical properties of Al-10Ce-3Mg alloys were significantly improved due to the addition of Zn element. The alloy containing 5 wt.% Zn had the best tensile properties with an ultimate tensile strength of 210 MPa and a yield strength of 171MPa, which were 21% and 77% higher than those of the alloy without Zn, respectively. The alloy containing 5 wt.% Zn demonstrated a superior retention ratio of tensile strength at 200–300 °C, indicating that the alloy has excellent heat resistance. The improvement in the mechanical properties is primarily attributed to second-phase strengthening and solid solution strengthening. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of targeted therapies, achieving a maximal safe resection still remains a critical prognosis factor in diffuse low-grade gliomas and represents the goal to reach for neurosurgeons who manage these tumors. Whereas fluorescence-guided surgery, using 5-aminolevulinic acid or even fluorescein sodium significantly increases the extent of resection of high-grade gliomas, its relevance for the resection of low-grade gliomas is very limited. However, new intraoperative techniques such as spectroscopic detection of 5-aminolevulinic acid-induced fluorescence or confocal laser endomicroscopy have been developed in order to increase the sensitivity of fluorescence detection in low-grade gliomas or to generate optic biopsies, respectively. Therefore, the goal of this review was to sum up the limitations of macroscopic fluorescence detection in low-grade gliomas and to highlight how new technologies likely to be implemented in the surgical routine in the near future, could overcome these limitations. Diffuse low-grade gliomas are infiltrative tumors whose margins are not distinguishable from the adjacent healthy brain parenchyma. The aim was to precisely examine the results provided by the intraoperative use of macroscopic fluorescence in diffuse low-grade gliomas and to describe the new fluorescence-based techniques capable of guiding the resection of low-grade gliomas. Only about 20% and 50% of low-grade gliomas are macroscopically fluorescent after 5-amino-levulinic acid (5-ALA) or fluorescein sodium intake, respectively. However, 5-ALA is helpful for detecting anaplastic foci, and thus choosing the best biopsy targets in diffuse gliomas. Spectroscopic detection of 5-ALA-induced fluorescence can detect very low and non-macroscopically visible concentrations of protoporphyrin IX, a 5-ALA metabolite, and, consequently, has excellent performances for the detection of low-grade gliomas. Moreover, these tumors have a specific spectroscopic signature with two fluorescence emission peaks, which is useful for distinguishing them not only from healthy brain but also from high-grade gliomas. Confocal laser endomicroscopy can generate intraoperative optic biopsies, but its sensitivity remains limited. In the future, the coupled measurement of autofluorescence and induced fluorescence, and the introduction of fluorescence detection technologies providing a wider field of view could result in the development of operator-friendly tools implementable in the operative routine. [ABSTRACT FROM AUTHOR]

During magnetic-resonance-guided focused ultrasound ablation of the ventral intermediate thalamic nucleus (VIM) for essential tremor (ET) and Parkinson's disease (PD), targeting is generally performed using a standard atlas-based stereotactic approach. The purpose of our work is to evaluate the anatomic variations in the venous vasculature of the thalamus in patients treated with MRgFUS, as a possible landmark for targeting. We retrospectively evaluated the relationship between the obtained thalamotomy lesion and the ipsilateral superior thalamic vein (STV). A total of 36 patients (25 ET and 11 PD) who underwent MRgFUS treatment were evaluated, and the STV was studied with susceptibility weighted imaging (SWI) sequences. Based on the axial SWI images, the distance between the STV and the center of the lesion at the presumed site of the VIM was measured in follow-up MRI images one month after treatment. Statistical analysis shows that there is a correlation between the STV and the presumed site of the VIM. The STV visible in SWI could be used as an additional, real-time, and patient-specific anatomical landmark for VIM identification during MR examination and just before and during FUS treatment. [ABSTRACT FROM AUTHOR]

Traumatic vascular injuries consist of direct or indirect damage to arteries and/or veins and account for 3% of all traumatic injuries. Typical consequences are hemorrhage and ischemia. Vascular injuries of the extremities can occur isolated or in association with major trauma and other organ injuries. They account for 1–2% of patients admitted to emergency departments and for approximately 50% of all arterial injuries. Lower extremities are more frequently injured than upper ones in the adult population. The outcome of vascular injuries is strictly correlated to the environment and the time background. Treatment can be challenging, notably in polytrauma because of the dilemma of which injury should be prioritized, and treatment delay can cause disability or even death, especially for limb vascular injury. Our purposes are to discuss the role of computed tomography angiography (CTA) in the diagnosis of vascular trauma and its optimized protocol to achieve a definitive diagnosis and to assess the radiological signs of vascular injuries and the possible pitfalls. [ABSTRACT FROM AUTHOR]

Background: Recurrence in glioblastoma lacks a standardized treatment, prompting an exploration of re-irradiation's efficacy. Methods: A comprehensive systematic review from January 2005 to May 2023 assessed the role of MRI sequences in recurrent glioblastoma re-irradiation. The search criteria, employing MeSH terms, targeted English-language, peer-reviewed articles. The inclusion criteria comprised both retrospective and prospective studies, excluding certain types and populations for specificity. The PICO methodology guided data extraction, and the statistical analysis employed Chi-squared tests via MedCalc v22.009. Results: Out of the 355 identified studies, 81 met the criteria, involving 3280 patients across 65 retrospective and 16 prospective studies. The key findings indicate diverse treatment modalities, with linac-based photons predominating. The median age at re-irradiation was 54 years, and the median time interval between radiation courses was 15.5 months. Contrast-enhanced T1-weighted sequences were favored for target delineation, with PET-imaging used in fewer studies. Re-irradiation was generally well tolerated (median G3 adverse events: 3.5%). The clinical outcomes varied, with a median 1-year local control rate of 61% and a median overall survival of 11 months. No significant differences were noted in the G3 toxicity and clinical outcomes based on the MRI sequence preference or PET-based delineation. Conclusions: In the setting of recurrent glioblastoma, contrast-enhanced T1-weighted sequences were preferred for target delineation, allowing clinicians to deliver a safe and effective therapeutic option; amino acid PET imaging may represent a useful device to discriminate radionecrosis from recurrent disease. Future investigations, including the ongoing GLIAA, NOA-10, ARO 2013/1 trial, will aim to refine approaches and standardize methodologies for improved outcomes in recurrent glioblastoma re-irradiation. [ABSTRACT FROM AUTHOR]

Glial tumors represent the leading etiology of primary brain tumors. Their particularities lie in (i) their location in a highly functional organ that is difficult to access surgically, including for biopsy, and (ii) their rapid, anisotropic mode of extension, notably via the fiber bundles of the white matter, which further limits the possibilities of resection. The use of mathematical tools enables the development of numerical models representative of the oncotype, genotype, evolution, and therapeutic response of lesions. The significant development of digital technologies linked to high-resolution NMR exploration, coupled with the possibilities offered by AI, means that we can envisage the creation of digital twins of tumors and their host organs, thus reducing the use of physical sampling. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Diseases (IBD), mainly Ulcerative Colitis (UC) and Crohn's Disease (CD), are disorders characterized by chronic inflammation with severe morbidity and long-term disabling quality of life outcomes. UC mainly affects the mucosal and sub-mucosal layers of the colon, without embracing the peri-intestinal structures. Considering the predominant mucosal location of UC inflammation, the implementation of transmural evaluation by cross-sectional imaging techniques, mainly Intestinal Ultrasound (IUS), has been left behind for ages, especially if compared to CD. Nevertheless, studies analyzing intestinal ultrasound parameters accuracy in disease activity detection reported a good-to-optimal correlation of IUS markers with colonic inflammation, suggesting comparable feasibility of IUS monitoring in UC as in CD. The easy-to-use, costless and point-of-care available status of IUS is therefore crucial in order to improve the diagnostic process and, according to the recent literature, to monitor the response to treatment leading to speeding up decision making and therapy adjustments. Recent studies have demonstrated the correlation between transmural healing in UC with favorable outcomes even in the long term. An evidence gap still exists in the assessment of the rectum, with trans-perineal ultrasound (TPUS) a potential answer to reach a more precise evaluation of rectal inflammation. Eventually, IUS is also increasingly showing promises in emergent or post-surgical UC settings, considering various efforts put in line to demonstrate its feasibility in predicting response to salvage therapy for surgery avoidance and in studying inflammation relapse after procto-colectomy with ileo-pouch–anal anastomosis (IPAA) creation. [ABSTRACT FROM AUTHOR]

Simple Summary: Anatomical variants are traits that differ between individuals. The sphenoid bone has numerous variant features, such as foramina and canals, that may be involved in surgical procedures. This study on CT-scan images describes the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal and their relationships. For the first time, a correlation between the foramen of Vesalius and the canaliculus innominatus was found. This topic is especially important in cranial base surgical procedures that may involve tumor treatment. The sphenoid bone presents several anatomical variations, including accessory foramina, such as the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal, which may be involved in tumor invasion or surgery of surrounding structures. Therefore, clinicians and surgeons have to consider these variants when planning surgical interventions of the cranial base. The prevalence of each variant is reported in the published literature, but very little information is available on the possible correlation among different variants. Here, 300 CT scans of patients (equally divided among males and females) were retrospectively assessed to investigate the presence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal. Possible differences in the prevalence of each accessory foramen according to sex were assessed, as well as possible correlations among different variants through the Chi-square test (p < 0.01). Overall, the prevalence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal was 30.7%, 67.7%, 14.0% and 35.3%, respectively, without any difference according to sex (p > 0.01). A significant positive correlation was found between the foramen of Vesalius and canaliculus innominatus, both in males and in females (p < 0.01). In detail, subjects with canaliculus innominatus in 85.7–100.0% of cases also showed the foramen of Vesalius, independently from sex and side. The present study provided novel data about the prevalence of four accessory foramina of the sphenoid bone in an Italian population, and a correlation between the foramen of Vesalius and the canaliculus innominatus was found for the first time. As these accessory foramina host neurovascular structures, the results of this study are thus useful for appropriate planning surgical procedures that are tailored to the anatomical configuration of the patient and for improving techniques to avoid accidental injuries in cranial base surgery. Knowledge of the topography, frequencies and the presence/absence of these additional foramina are pivotal for a successful procedure. Clinicians and surgeons may benefit from these novel data for appropriate recognition of the variants, decision-making, pre-operative and treatment planning, improvement of the procedures, screening of patients and prevention of misdiagnosis. [ABSTRACT FROM AUTHOR]

The diagnosis of large vestibular schwannomas (VS) with retained useful hearing has become increasingly common. Preservation of facial nerve (FN) function has improved using intraoperative EMG monitoring, hearing preservation remains challenging, with the recent use of cochlear nerve action potential (CNAP) monitoring. This prospective longitudinal series of VS with useful hearing operated on using a retrosigmoid approach included 37 patients with a mean largest extrameatal VS. diameter of 25 ± 8.7 mm (81% of Koos stage 4). CNAP was detected in 51% of patients, while auditory brainstem responses (ABR) were present in 22%. Patients were divided into two groups based on the initial intraoperative CNAP status, whether it was present or absent. FN function was preserved (grade I–II) in 95% of cases at 6 months. Serviceable hearing (class A + B) was preserved in 16% of the cases, while 27% retained hearing with intelligibility (class A–C). Hearing with intelligibility (class A–C) was preserved in 42% of cases when CNAP could be monitored in the early stages of VS resection versus 11% when it was initially absent. Changes in both the approach to the cochlear nerve and VS resection are mandatory in preserving CNAP and improve the rate of hearing preservation. [ABSTRACT FROM AUTHOR]

The current study of Al alloys aims to improve their high-temperature mechanical properties by forming intermetallic precipitates with high-temperature stability. Using rare earth elements (RE) to achieve this goal increases the production cost and, hence, minimizes the economic advantage of the conventional casting processes. Therefore, alternative additives/methods with reasonable costs become mandatory. Al-Ce alloys were found to be a promising group of alloys. Cerium is the most economically abundant RE that can be added to aluminum alloys. The main intermetallic phase, i.e., Al11Ce3, is characterized by its high-temperature stability compared to other Al-based intermetallic compounds. Several research works modified the morphology of the stable Al11Ce3 phase to enhance the high-temperature properties of Al-Ce alloys. These methods were heat treatment, chemical modification, and solidification processing. This review article summarizes the "few" available research works, that studied the influence of solidification processing on the microstructure features of Al-Ce alloys. Among the solidification processing techniques available, special attention was given to microstructure processing via ultrasonic treatment and the corresponding effects on mechanical properties and electrochemical behavior. Future research points were also proposed. [ABSTRACT FROM AUTHOR]

Gemella is a catalase-negative, facultative anaerobic, Gram-positive coccus that is commensal in humans but can become opportunistic and cause severe infectious diseases, such as infective endocarditis. Few studies have tested the antimicrobial susceptibility of Gemella. We tested its antimicrobial susceptibility to 27 drugs and defined the resistant genes using PCR in 58 Gemella strains, including 52 clinical isolates and six type strains. The type strains and clinical isolates included 22 G. morbillorum, 18 G. haemolysans (GH) group (genetically indistinguishable from G. haemolysans and G. parahaemolysans), 13 G. taiwanensis, three G. sanguinis, and two G. bergeri. No strain was resistant to beta-lactams and vancomycin. In total, 6/22 (27.3%) G. morbillorum strains were erythromycin- and clindamycin-resistant ermB-positive, whereas 4/18 (22.2%) in the GH group, 7/13 (53.8%) G. taiwanensis, and 1/3 (33.3%) of the G. sanguinis strains were erythromycin-non-susceptible mefE- or mefA-positive and clindamycin-susceptible. The MIC90 of minocycline and the ratios of tetM-positive strains varied across the different species—G. morbillorum: 2 µg/mL and 27.3% (6/22); GH group: 8 µg/mL and 27.8% (5/18); G. taiwanensis: 8 µg/mL and 46.2% (6/13), respectively. Levofloxacin resistance was significantly higher in G. taiwanensis (9/13 69.2%) than in G. morbillorum (2/22 9.1%). Levofloxacin resistance was associated with a substitution at serine 83 for leucine, phenylalanine, or tyrosine in GyrA. The mechanisms of resistance to erythromycin and clindamycin differed across Gemella species. In addition, the rate of susceptibility to levofloxacin differed across Gemella sp., and the quinolone resistance mechanism was caused by mutations in GyrA alone. [ABSTRACT FROM AUTHOR]

Myocardial bridging (MB) is a congenital coronary anomaly in which a segment of a coronary artery, most frequently the left anterior descending artery, deviates from its epicardial route by passing through the myocardium. The advent of cardiac computed tomography angiography (CCTA), equipped with its multiplane and three-dimensional functionalities, has notably enhanced the ability to identify MBs. Furthermore, novel post-processing methods have recently emerged to extract functional insights from anatomical evaluations. MB is generally considered a benign entity with very good survival rates; however, there is an increasing volume of evidence that certain MB characteristics may be associated with cardiovascular morbidity. This review is intended to depict the diagnostic and prognostic role of CCTA in the MB context. [ABSTRACT FROM AUTHOR]

The rapid evolution of 5G and beyond technologies has sparked an unprecedented surge in the need for networking infrastructure that can deliver high speed, minimal latency, and remarkable flexibility. The programmable data plane, which enables the dynamic reconfiguration of network functions and protocols, is becoming increasingly important in meeting these requirements. This paper provides an overview of the current state of the art in programmable data planes implemented in 5G and beyond architectures. It proposes a classification of the reviewed studies based on system architecture and specific use cases. Furthermore, the article surveys the primary applications of programmable devices in emerging telecommunication networks, such as tunneling and forwarding, network slicing, cybersecurity, and in-band telemetry. Finally, this publication summarizes the open research challenges and future directions. In addition to offering a comprehensive review of programmable data plane applications in telecommunication networks, this article aims to guide further research in this promising field for network operators and researchers alike. [ABSTRACT FROM AUTHOR]

Varicocele treatment in infertility still remains controversial. It is clear, in fact, that in many patients, varicocele has no impact on fertility. Recent scientific evidence demonstrated that varicocele treatment is beneficial in improving semen parameters and pregnancy rate when an appropriate selection of patients is made. The purpose of treating varicocele in adults is mainly to improve current fertility status. On the other hand, the goal of treatment in adolescents is to prevent testicular injury and maintain testicular function for future fertility. Hence, the key to the success of varicocele treatment seems to be a correct indication. The aim of this study is to review and summarize current evidence in managing varicocele treatment focusing on the controversies regarding surgical indications in adolescent and adult patients, and in other specific situations such as azoospermia, bilateral or subclinical varicocele, and prior to ART. [ABSTRACT FROM AUTHOR]

Simple Summary: This scientific research characterizes the recurrence pattern of patients with glioblastoma after trimodality treatment, neurosurgery and radiation therapy, either intensity modulated radiation therapy (IMRT) or volumetric intensity modulated arc therapy (VMAT), as well as concurrent chemotherapy in a clinical setting based on daily image-guided radiation therapy (IGRT) at the West German Cancer Center. This study underlines the importance of reconsideration of clinical target volume margins in the clinical routine. Larger radiation therapy margins may decrease the proportion of out-field recurrences, but an effect on overall survival is highly questionable. Background: While prognosis of glioblastoma after trimodality treatment is well examined, recurrence pattern with respect to the delivered dose distribution is less well described. Therefore, here we examine the gain of additional margins around the resection cavity and gross-residual-tumor. Methods: All recurrent glioblastomas initially treated with radiochemotherapy after neurosurgery were included. The percentage overlap of the recurrence with the gross tumor volume (GTV) expanded by varying margins (10 mm to 20 mm) and with the 95% and 90% isodose was measured. Competing-risks analysis was performed in dependence on recurrence pattern. Results: Expanding the margins from 10 mm to 15 mm, to 20 mm, to the 95%- and 90% isodose of the delivered dose distribution with a median margin of 27 mm did moderately increase the proportion of relative in-field recurrence volume from 64% to 68%, 70%, 88% and 88% (p < 0.0001). Overall survival of patients with in-and out-field recurrence was similar (p = 0.7053). The only prognostic factor significantly associated with out-field recurrence was multifocality of recurrence (p = 0.0037). Cumulative incidences of in-field recurrences at 24 months were 60%, 22% and 11% for recurrences located within a 10 mm margin, outside a 10 mm margin but within the 95% isodose, or outside the 95% isodose (p < 0.0001). Survival from recurrence was improved after complete resection (p = 0.0069). Integrating these data into a concurrent-risk model shows that extending margins beyond 10 mm has only small effects on survival hardly detectable by clinical trials. Conclusions: Two-thirds of recurrences were observed within a 10 mm margin around the GTV. Smaller margins reduce normal brain radiation exposure allowing for more extensive salvage radiation therapy options in case of recurrence. Prospective trials using margins smaller than 20 mm around the GTV are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Vestibular schwannomas are benign tumors of the eighth cranial nerve, caused by mutations in the NF2 gene encoding the tumor suppressor, merlin. A standard treatment for vestibular schwannoma is radiation therapy; however, radiation can cause sudden or progressive hearing loss in patients over time. Most commonly, vestibular schwannomas are treated with stereotactic radiation in one or multiple fractions. In this study, we investigated the effect of different radiation fractionation regimens on hearing in rats, loss of auditory hair cells, and control of tumor growth. Our work suggests that hypofractionation may improve the therapeutic ratio by increasing the likelihood of hearing preservation whilst equally reducing proliferation of tumor cells in comparison with single fraction. Further investigations are needed to understand radiation mechanisms and identify new therapeutic options to reduce hearing loss and enhance tumor control in vestibular schwannoma. Background: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). Methods: Adult rats received cochlear irradiation with single fraction (0 to 18 Gray [Gy]) or hypofractionated radiation. Auditory brainstem response (ABR) testing was performed for 24 weeks. AHC viabilities were determined using immunohistochemistry. Neonatal rat cochleae were harvested after irradiation, and gene- and cell-based assays were conducted. MD-SCs were irradiated, and viability assays and immunofluorescence for DNA damage and cell cycle markers were performed. Results: Radiation caused dose-dependent and progressive HL in rats and AHC losses by promoting expression of apoptosis-associated genes and proteins. When compared to 12 Gy single fraction, hypofractionation caused smaller ABR threshold and pure tone average shifts and was more effective at reducing MD-SC viability. Conclusions: Investigations into the mechanisms of radiation ototoxicity and VS radiobiology will help determine optimal radiation regimens and identify potential therapies to mitigate radiation-induced HL and improve VS tumor control. [ABSTRACT FROM AUTHOR]

Heat-treated aluminum–silicon (Al-Si)-based alloys have dominated the cast lightweight alloy industry for several decades. However, in the last decade, Al-Ce-based alloys have shown promise in replacing Al-Si alloys as they remove the need for costly heat treatments. As the properties of Al-Ce alloys depend on the as-cast microstructure, it is important to characterize the solidification kinetics of these alloys. Therefore, this study focused on characterizing the solidification of an Al-Ce alloy with additions of Ni and Mn (nominal composition Al-12.37Ce-3.26Ni-0.94Mn-0.12Fe in weight percent). The alloy was cast in a wedge mold configuration, resulting in cooling rates between 0.18 and 14.27 °C/s. Scanning electron microscopy (SEM) coupled with the energy dispersive x-ray spectroscopy (EDS) and differential scanning calorimetry (DSC) techniques characterized the evolution rate of solid phases. The SEM/EDS data revealed that an Al10CeMn2 phase was present at higher cooling rates. At lower cooling rates, near the center of the casting, a primary Al23Ce4Ni6 phase was more present. It was observed that up to 2.6 atomic percent (at.%) of Mn was dissolved in this primary Al23Ce4Ni6 phase, thereby removing a large portion of the available Mn for forming the Al10CeMn2 phase. DSC analysis showed differences in the samples' liquidus temperatures, which indicated compositional variations. Inductively coupled plasma–atomic emission spectroscopy (ICP-OES) and Scheil solidification simulations correlated the compositional differences with phase formation, which agreed with the SEM and DSC results. This experiment provides insight into novel Al-Ce-Ni-Mn alloys and where their potential lies in industrial applications. [ABSTRACT FROM AUTHOR]

The use of IoT devices has increased rapidly in recent times. While the development of new devices is moving quickly, and as prices are being forced down, the costs of developing such devices also needs to be reduced. IoT devices are now trusted with more critical tasks, and it is important that they behave as intended and that the information they process is protected. It is not always the IoT device itself that is the target of a cyber attack, but rather, it can be a tool for another attack. Home consumers, in particular, expect these devices to be easy to use and set up. However, to reduce costs, complexity, and time, security measures are often cut down. To increase awareness and knowledge in IoT security, education, awareness, demonstrations, and training are necessary. Small changes may result in significant security benefits. With increased awareness and knowledge among developers, manufacturers, and users, they can make choices that can improve security. To increase knowledge and awareness in IoT security, a proposed solution is a training ground for IoT security, an IoT cyber range. Cyber ranges have received more attention lately, but not as much in the IoT field, at least not what is publicly available. As the diversity in IoT devices is large with different vendors, architectures, and components and peripherals, it is difficult to find one solution that fits all IoT devices. To some extent, IoT devices can be emulated, but it is not feasible to create emulators for all types of devices. To cover all needs, it is necessary to combine digital emulation with real hardware. A cyber range with this combination is called a hybrid cyber range. This work surveys the requirements for a hybrid IoT cyber range and proposes a design and implementation of a range that fulfills those requirements. [ABSTRACT FROM AUTHOR]

Negative, tragic, traumatic and suffering representations continue to dominate the discussions and content on social media in the stories and content related to Syrian refugees. The public, while browsing social media, finds that this representation is the dominant one that dominates the image of refugees. Thus, there is a potential risk that the public's compassion will be negatively affected after repeated exposure to the dominant representation in light of the inability to put an end to that situation. This study discusses the perspectives of Syrian refugees living in Jordan and Turkey on whether they feel such repeated negative and tragic content about their stories and news on social media could affect the empathy of the audience in hosting communities with them, especially since social media is an open-source platform that all people at any time and from any place can post, re-share, comment and create content by adding texts, photos and videos, not like traditional media, which are controlled more than social media platforms for open participatory content. This study aims to explore how a vulnerable population, such as Syrian refugees in Istanbul and Amman, sees the effect of negative representation on themselves and their image in the hosting communities and does not aim to examine or offer any conclusion as to whether the public in Jordan and Turkey have experienced compassion fatigue. This study provides and extracts some useful insights, but proves no hypotheses or conclusive evidence regarding the occurrence of compassion fatigue in the public; thus, the study opens the door for the debate on the role that social media plays as a source of compassion fatigue among citizens towards refugees, mainly when they are repeatedly exposed to such negative stories and content, as well as calls for an in-depth and extensive study on the topic from the point of view of the public and citizens in the hosting countries, after examining, understanding and analyzing the opinions and their dimensions of the sample of refugees in this study. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) represents the most common and aggressive central nervous system tumor associated with a poor prognosis. The aim of this study was to depict the role of intraoperative imaging techniques in GBM surgery and how they can ensure the maximal extent of resection (EOR) while preserving the functional outcome. The authors conducted a systematic review following PRISMA guidelines on the PubMed/Medline and Scopus databases. A total of 1747 articles were identified for screening. Studies focusing on GBM-affected patients, and evaluations of EOR and functional outcomes with the aid of advanced image-guided techniques were included. The resulting studies were assessed for methodological quality using the Risk of Bias in Systematic Review tool. Open Science Framework registration DOI 10.17605/OSF.IO/3FDP9. Eighteen studies were eligible for this systematic review. Among the selected studies, eight analyzed Sodium Fluorescein, three analyzed 5-aminolevulinic acid, two evaluated IoMRI imaging, two evaluated IoUS, and three evaluated multiple intraoperative imaging techniques. A total of 1312 patients were assessed. Gross Total Resection was achieved in the 78.6% of the cases. Follow-up time ranged from 1 to 52 months. All studies assessed the functional outcome based on the Karnofsky Performance Status scale, while one used the Neurologic Assessment in Neuro-Oncology score. In 77.7% of the cases, the functional outcome improved or was stable over the pre-operative assessment. Combining multiple intraoperative imaging techniques could provide better results in GBM surgery than a single technique. However, despite good surgical outcomes, patients often present a neurocognitive decline leading to a marked deterioration of the quality of life. Advanced intraoperative image-guided techniques can allow a better understanding of the anatomo-functional relationships between the tumor and the surrounding brain, thus maximizing the EOR while preserving functional outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Differential diagnosis among primary and secondary central nervous system tumors, the assessment of tumoral therapy response, the correlation between imaging and prognosis, and biomolecular findings remain the main diagnostic challenges in the neuro-oncology imaging field. In the literature, novel, sophisticated MRI sequences and applications of artificial intelligence are frequently researched with this goal in mind; anyway, some of these tools are still not applicable in clinical practice. On the contrary, Diffusion Weighted Imaging (DWI) is a sequence commonly used in everyday clinical practice that can give information in terms of tumor grading, differential diagnosis, molecular profile, and response to therapy. DWI is an imaging technique commonly used for the assessment of acute ischemia, inflammatory disorders, and CNS neoplasia. It has several benefits since it is a quick, easily replicable sequence that is widely used on many standard scanners. In addition to its normal clinical purpose, DWI offers crucial functional and physiological information regarding brain neoplasia and the surrounding milieu. A narrative review of the literature was conducted based on the PubMed database with the purpose of investigating the potential role of DWI in the neuro-oncology field. A total of 179 articles were included in the study. [ABSTRACT FROM AUTHOR]

With the advancement of data-acquisition systems, information technology, and network technologies, the energy and power system has entered the deep integration of the cyber and physical sides as known as cyber-physical energy and power system (CPEPS) leading to more attention from researchers and practitioners in industry. The feedback loops in which physical processes affect cyber parts and vice versa, therefore, can gain greater efficiency, resilience, and intelligence through the data exchange process between two layers. The concept of CPEPS has been existed for a long time and its applications are gradually increasing in the real world, however, there has been still many potential risks and challenges in the research and development process. Simulation method is a common and simple approach for the purpose of analyzing, evaluating, and considering solutions before actual implementation. For this purpose, this paper provides first the framework of CPEPS, and current applications and challenges that researchers are facing. Then, the next section is the overview of simulation methods with different software and tools in CPEPS research in order to provide researchers with an optimal approach to the ongoing and further research towards the transition of digitalization on energy and power system. [ABSTRACT FROM AUTHOR]

Purpose. For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. Material/Methods: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2–3 months. Results: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15–36 Gy), and median fractions was 5 (range 1–6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6–56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3–4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. Conclusion. Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed. [ABSTRACT FROM AUTHOR]

The connectivity advances in industrial control systems have also increased the possibility of cyberattacks in industry. Thus, security becomes crucial in critical infrastructures, whose services are considered essential in fields such as manufacturing, energy or public health. Although theoretical and formal approaches are often proposed to advance in the field of industrial cybersecurity, more experimental efforts in realistic scenarios are needed to understand the impact of incidents, assess security technologies or provide training. In this paper, an approach for cybersecurity experimentation is proposed for several industrial areas. Aiming at a high degree of flexibility, the Critical Infrastructure Cybersecurity Laboratory (CICLab) is designed to integrate both real physical equipment with computing and networking infrastructure. It provides a platform for performing security experiments in control systems of diverse sectors such as industry, energy and building management. They allow researchers to perform security experimentation in realistic environments using a wide variety of technologies that are common in these control systems, as well as in the protection or security analysis of industrial networks. Furthermore, educational developments can be made to meet the growing demand of security-related professionals. [ABSTRACT FROM AUTHOR]

Simple Summary: 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used in neurosurgery for intraoperative identification of high-grade glioma tissue. In this paper, using a fluorescence microscopy analysis on human tumor specimens, we assessed the actual number of fluorescence-positive tumor cells both in low-grade and high-grade glioma, and the ability of 5-ALA to cross the blood–brain barrier (BBB). We found that in high-grade gliomas, 32.7–75.5 percent of cells display 5-ALA induced PpIX fluorescence, whereas in low-grade gliomas the tumor cells did not fluoresce following 5-ALA. Immunofluorescence for BBB components suggested that 5-ALA does not cross the un-breached BBB. These findings are of crucial importance in planning neurosurgical resection of gliomas. 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used by neurosurgeons to identify the tumor cells of high-grade gliomas during operation. However, the issue of whether 5-ALA-induced PpIX fluorescence consistently stains all the tumor cells is still debated. Here, we assessed the cytoplasmatic signal of 5-ALA by fluorescence microscopy in a series of human gliomas. As tumor markers, we used antibodies against collapsin response-mediated protein 5 (CRMP5), alpha thalassemia/mental retardation syndrome X-linked (ATRX), and anti-isocitrate dehydrogenase 1 (IDH1). In grade III–IV gliomas, the signal induced by 5-ALA was detected in 32.7–75.5 percent of CRMP5-expressing tumor cells. In low-grade gliomas (WHO grade II), the CRMP5-expressing tumor cells did not fluoresce following 5-ALA. Immunofluorescence with antibodies that stain various components of the blood–brain barrier (BBB) suggested that 5-ALA does not cross the un-breached BBB, in spite of its small dimension. To conclude, 5-ALA-induced PpIX fluorescence has an established role in high-grade glioma surgery, but it has limited usefulness in surgery for low-grade glioma, especially when the BBB is preserved. [ABSTRACT FROM AUTHOR]

Tissue engineering is an interdisciplinary field of science that has developed very intensively in recent years. The first part of this review describes materials with medical and dental applications from the following groups: metals, polymers, ceramics, and composites. Both positive and negative sides of their application are presented from the point of view of medical application and mechanical properties. A variety of techniques for the manufacture of biomedical components are presented in this review. The main focus of this work is on additive manufacturing and 3D printing, as these modern techniques have been evaluated to be the best methods for the manufacture of medical and dental devices. The second part presents devices for skull bone reconstruction. The materials from which they are made and the possibilities offered by 3D printing in this field are also described. The last part concerns dental transitional implants (scaffolds) for guided bone regeneration, focusing on polylactide–hydroxyapatite nanocomposite due to its unique properties. This section summarises the current knowledge of scaffolds, focusing on the material, mechanical and biological requirements, the effects of these devices on the human body, and their great potential for applications. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS. [ABSTRACT FROM AUTHOR]

This study sought to explore the existence and clinical significance of intratumoral heterogeneity of proliferative potential in vestibular schwannoma (VS). Rapid intraoperative flow cytometry was utilized with raw samples to measure the proliferative ability of VS. The proliferation index (PI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. A total of 66 specimens (26 from the intrameatal portion and 40 from the cisternal portion) were obtained from 34 patients with VS. There was a moderate correlation between the PI and MIB-1 labelling index values (R = 0.57, p < 0.0001). In contrast, the patterns of heterogeneity, represented by the proportion of intrameatal PI to cisternal PI, were associated with tumor size (p = 0.03). In addition, preoperative hearing tended to be poor in cases where the intrameatal PI was higher than the cisternal PI (p = 0.06). Our data demonstrated the presence of intratumoral heterogeneity of proliferative potential in VS and its relationship with tumor characteristics. The results of this study may advocate the resection of the intrameatal portion of large VSs treated with planned subtotal resection, especially in cases of poor preoperative hearing function. [ABSTRACT FROM AUTHOR]

Advances in neuroimaging of the preterm infant have enhanced the ability to detect brain injury. This added information has been a blessing and a curse. Neuroimaging, particularly with magnetic resonance imaging, has provided greater insight into the patterns of injury and specific vulnerabilities. It has also provided a better understanding of the microscopic and functional impacts of subtle and significant injuries. While the ability to detect injury is important and irresistible, the evidence for how these injuries link to specific long-term outcomes is less clear. In addition, the impact on parents can be profound. This narrative summary will review the history and current state of brain imaging, focusing on magnetic resonance imaging in the preterm population and the current state of the evidence for how these patterns relate to long-term outcomes. [ABSTRACT FROM AUTHOR]

Co-simulation is an emerging method for cyber-physical energy system (CPES) assessment and validation. Combining simulators of different domains into a joint experiment, co-simulation provides a holistic framework to consider the whole CPES at system level. In this paper, we present a systematic structuration of co-simulation based on a conceptual point of view. A co-simulation framework is then considered in its conceptual, semantic, syntactic, dynamic and technical layers. Coupling methods are investigated and classified according to these layers. This paper would serve as a solid theoretical base for specification of future applications of co-simulation and selection of coupling methods in CPES assessment and validation. [ABSTRACT FROM AUTHOR]

The complexity of the power grid, in conjunction with the ever increasing demand for electricity, creates the need for efficient analysis and control of the power system. The evolution of the legacy system towards the new smart grid intensifies this need due to the large number of sensors and actuators that must be monitored and controlled, the new types of distributed energy sources that need to be integrated and the new types of loads that must be supported. At the same time, integration of human-activity awareness into the smart grid is emerging and this will allow the system to monitor, share and manage information and actions on the business, as well as the real world. In this context, modeling and simulation is an invaluable tool for system behavior analysis, energy consumption estimation and future state prediction. In this paper, we review current smart grid simulators and approaches for building and user behavior modeling, and present a federated smart grid simulation framework, in which building, control and user behavior modeling and simulation are decoupled from power or network simulators and implemented as discrete components. This framework enables evaluation of the interactions between the communication infrastructure and the power system taking into account the human activities, which are at the focus of emerging energy-related applications that aim to shape user behavior. Validation of the key functionality of the proposed framework is also presented. [ABSTRACT FROM AUTHOR]

Simple Summary: In the next decades, the incidence of patients with glioblastoma (GBM) will markedly increase due to the growth of the elderly population. Despite the increasing incidence of GBM, elderly patients are frequently excluded from clinical studies and thus, only few data are available specifically focusing on the elderly population. In the current study, we aimed to investigate the efficacy, outcome, and safety of surgically-treated GBM including resections and biopsies in the 5-ALA era in a large elderly cohort of altogether 272 patients. Our data of this large elderly cohort demonstrate for the first time the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients. Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm3), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Vestibular schwannomas (VS) are intracranial tumors that originate from the Schwann cells of the vestibulocochlear nerve and cause hearing loss and dizziness. Although radiation therapy is a common treatment for VS, some irradiated tumors do not respond well and continue to grow, requiring additional therapies such as surgery. Little is known about the molecular mechanisms behind the normal response of VS to radiation therapy and why some VS are resistant to radiation. Thus, we aimed to review the current understanding of radiation response and resistance in VS through an in-depth summary of the DNA damage and cell cycle response to ionizing radiation. A better understanding of the radiobiology of VS can help guide future investigations looking at optimal radiation dosing strategies, unique targets for intervention, and novel therapies to improve patient outcomes. Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8–10% of all intracranial tumors and are the most common tumors of the cerebellopontine angle. These tumors are typically managed with observation, radiation therapy, or microsurgical resection. Of the VS that are irradiated, there is a subset of tumors that are radioresistant and continue to grow; the mechanisms behind this phenomenon are not fully understood. In this review, the authors summarize how radiation causes cellular and DNA injury that can activate (1) checkpoints in the cell cycle to initiate cell cycle arrest and DNA repair and (2) key events that lead to cell death. In addition, we discuss the current knowledge of VS radiobiology and how it may contribute to clinical outcomes. A better understanding of VS radiobiology can help optimize existing treatment protocols and lead to new therapies to overcome radioresistance. [ABSTRACT FROM AUTHOR]

Bowel ultrasound (BUS) is a non-invasive and accurate technique for assessing activity, extension of disease, and complications in inflammatory bowel diseases. The main advantages of BUS are its safety, reproducibility, and low costs. Ancillary technologies of BUS (i.e., color Doppler and wave elastography) could broaden the diagnostic power of BUS, allowing one to distinguish between inflammation and fibrosis. Considering the costs and invasiveness of colonoscopy and magnetic resonance, BUS appears as a fast, safe, and accurate technique. The objective measures of disease allow one to make clinical decisions, such as optimization, switch, or swap of therapy. Previous studies reported a sensitivity and a specificity of more than 90% compared to endoscopy and magnetic resonance. Lastly, transperineal ultrasound (TPUS) is a promising approach for the evaluation of perianal disease in Crohn's disease (CD) and disease activity in patients with ulcerative proctitis or pouchitis. Bowel ultrasound is being incorporated in the algorithm of managing inflammatory bowel diseases. Transmural healing evaluated through ultrasonography is emerging as a complementary target for disease treatment. In this review, we aimed to summarize and discuss the current evidence on BUS in the management of inflammatory bowel diseases and to address the challenges of a full validation of this technique. [ABSTRACT FROM AUTHOR]

Simple Summary: 5-aminolevulinic acid (5-ALA) is administered orally before brain tumor surgery to improve intraoperative visualization of tumor tissue. In comparison to most of the aggressive high-grade gliomas, only a few low-grade gliomas (LGG) demonstrate visible fluorescence during surgery. As the prognosis of these LGG is hard to predict, we aimed to investigate if visible fluorescence might be an intraoperative marker for aggressive tumor behavior in patients with LGG. According to our data, we could demonstrate that intraoperative visible fluorescence is a predictor for early tumor progression, transformation into more aggressive higher-grade tumors, and shorter survival in LGG patients. Therefore, visible 5-ALA fluorescence is an intraoperative marker of unfavorable prognosis during surgery of LGG. The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered. [ABSTRACT FROM AUTHOR]

The integration of improved control techniques with advanced information technologies enables the rapid development of smart grids. The necessity of having an efficient, reliable, and flexible communication infrastructure is achieved by enabling real-time data exchange between numerous intelligent and traditional electrical grid elements. The performance and efficiency of the power grid are enhanced with the incorporation of communication networks, intelligent automation, advanced sensors, and information technologies. Although smart grid technologies bring about valuable economic, social, and environmental benefits, testing the combination of heterogeneous and co-existing Cyber-Physical-Smart Grids (CP-SGs) with conventional technologies presents many challenges. The examination for both hardware and software components of the Smart Grid (SG) system is essential prior to the deployment in real-time systems. This can take place by developing a prototype to mimic the real operational circumstances with adequate configurations and precision. Therefore, it is essential to summarize state-of-the-art technologies of industrial control system testbeds and evaluate new technologies and vulnerabilities with the motivation of stimulating discoveries and designs. In this paper, a comprehensive review of the advancement of CP-SGs with their corresponding testbeds including diverse testing paradigms has been performed. In particular, we broadly discuss CP-SG testbed architectures along with the associated functions and main vulnerabilities. The testbed requirements, constraints, and applications are also discussed. Finally, the trends and future research directions are highlighted and specified. [ABSTRACT FROM AUTHOR]

Cyber–physical systems (CPSs) are an integral part of modern society; thus, enhancing these systems' reliability and resilience is paramount. Cyber–physical testbeds (CPTs) are a safe way to test and explore the interplay between the cyber and physical domains and to cost-effectively enhance the reliability and resilience of CPSs. Here a review of CPT elements, broken down into physical components (simulators, emulators, and physical hardware), soft components (communication protocols, network timing protocols), and user interfaces (visualization-dashboard design considerations) is presented. Various methods used to validate CPS performance are reviewed and evaluated for potential applications in CPT performance validation. Last, initial simulated results for a CPT design, based on the IEEE 33 bus system, are presented, along with a brief discussion on how model-based testing and fault–injection-based testing (using scaling and ramp-type attacks) may be used to help validate CPT performance. [ABSTRACT FROM AUTHOR]

Industrial Control Systems are an essential part of our daily lives and can be found in industries such as oil, utilities, and manufacturing. Rapid growth in technology has introduced industrial components with network capabilities that allow them to communicate with traditional computer networks, thus increasing their exposure to cyber-attacks. Current research on Industrial Control Systems suffer from lack of technical information as these systems are part of critical infrastructures. To overcome this, researchers have employed different types of testbeds to develop their mechanisms of cyber-attack detection and prevention. This manuscript describes, implements, and evaluates physical, hybrid, and virtual application of a clean water supply system developed for cybersecurity research. The results show that physical testbeds allow an understanding of the behaviour and dynamics of control components like sensors and actuators, which might be affected by external influences such as noise, vibration, temperature, and non-ideal device behaviour. Although, hybrid testbeds reduce the cost of implementation, they ignore the physical dynamics of the system as explained above. Virtual testbeds are the cheapest option in comparison with physical and hybrid testbeds; however, they provide a limited view of the control system operation that could have negative consequences when developing a detection/prevention system. [ABSTRACT FROM AUTHOR]

Simple Summary: In non-small cell lung cancer patients with brain metastases, combined Gamma Knife radiosurgery and immunotherapy or targeted therapy showed an increase in overall survival. The combination of Gamma Knife radiosurgery and immunotherapy or targeted therapy did not increase complications related to radiosurgery. Therefore, the combined treatment seems to be a safe and powerful treatment option for non-small cell lung cancer patients with brain metastases. The combination of Gamma Knife radiosurgery (GKRS) and systemic immunotherapy (IT) or targeted therapy (TT) is a novel treatment method for brain metastases (BMs) in non-small cell lung cancer (NSCLC). To elucidate the safety and efficacy of concomitant IT or TT on the outcome after GKRS, 496 NSCLC patients with BMs, who were treated with GKRS were retrospectively reviewed. The median time between the initial lung cancer diagnosis and the diagnosis of brain metastases was one month. The survival after the initial BM diagnosis was significantly longer than the survival predicted by prognostic BM scores. After the first Gamma Knife radiosurgery treatment (GKRS1), the estimated median survival was 9.9 months (95% CI = 8.3–11.4). Patients with concurrent IT or TT presented with a significantly longer survival after GKRS1 than patients without IT or TT (p < 0.001). These significant differences in the survival were also apparent among the four treatment groups and remained significant after adjustment for Karnofsky performance status scale (KPS), recursive partitioning analysis (RPA) class, sex, and multiple BMs. About half of all our patients (46%) developed new distant BMs after GKRS1. Of note, no statistically significant differences in the occurrence of radiation reaction, radiation necrosis, or intralesional hemorrhage in association with IT or TT at or after GKRS1 were observed. In NSCLC-BM patients, the concomitant use of GKRS and IT or TT showed an increase in overall survival without increased complications related to GKRS. Therefore, the combined treatment with GKRS and IT or TT seems to be a safe and powerful treatment option and emphasizes the role of radiosurgery in modern BM treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: 5-ALA Fluorescence Guided Surgery aims at extending the boundaries of glioblastoma (GBM) resection. It is based on the use of a fluorescent dye, 5-aminolevulinic acid (5-ALA). Depending on the fluorescence levels, it is possible to distinguish the core of the tumor, the infiltrating borders and the healthy tissue. Since GBM progression is supported by tumor cells and their interaction with the surrounding microenvironment, we hypothesized that 5-ALA intensity could identify microenvironments with different tumor supporting properties. Taking advantage of glioma-associated stem cells; a human in vitro model of the glioma microenvironment, we demonstrate that all regions of the tumor support the tumor growth, but through different pathways. This study highlights the importance of understanding the TME to obtain key information on GBM biology and develop new therapeutic approaches. The glioblastoma microenvironment plays a substantial role in glioma biology. However, few studies have investigated its spatial heterogeneity. Exploiting 5-ALA Fluorescence Guided Surgery (FGS), we were able to distinguish between the tumor core (ALA+), infiltrating area (ALA-PALE) and healthy tissue (ALA−) of the glioblastoma, based on the level of accumulated fluorescence. The aim of this study was to investigate the properties of the microenvironments associated with these regions. For this purpose, we isolated glioma-associated stem cells (GASC), resident in the glioma microenvironment, from ALA+, ALA-PALE and ALA− samples and compared them in terms of growth kinetic, phenotype and for the expression of 84 genes associated with cancer inflammation and immunity. Differentially expressed genes were correlated with transcriptomic datasets from TCGA/GTEX. Our results show that GASC derived from the three distinct regions, despite a similar phenotype, were characterized by different transcriptomic profiles. Moreover, we identified a GASC-based genetic signature predictive of overall survival and disease-free survival. This signature, highly expressed in ALA+ GASC, was also well represented in ALA PALE GASC. 5-ALA FGS allowed to underline the heterogeneity of the glioma microenvironments. Deepening knowledge of these differences can contribute to develop new adjuvant therapies targeting the crosstalk between tumor and its supporting microenvironment. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (5-ALA) is a fluorescent dye that after metabolization to Protoporphyrin IX (PpIX) by the heme biosynthesis pathway typically leads to visible fluorescence in WHO grade IV but not grade II gliomas. The exact mechanism for high PpIX levels in WHO grade IV gliomas and low PpIX levels in WHO grade II gliomas is not fully clarified. To detect relevant changes in mRNA expression, we performed an in-silico analysis of WHO grade II and IV glioma sequencing datasets provided by The Cancer Genome Atlas (TCGA) to investigate mRNA expression levels of relevant heme biosynthesis genes: Solute Carrier Family 15 Member 1 and 2 (SLC15A1 and SLC15A2), Aminolevulinate-Dehydratase (ALAD), Hydroxymethylbilane-Synthase (HMBS), Uroporphyrinogen-III-Synthase (UROS), Uroporphyrinogen-Decarboxylase (UROD), Coproporphyrinogen-Oxidase (CPOX), Protoporphyrinogen-Oxidase (PPOX), ATP-binding Cassette Subfamily B Member 6 (ABCB6)/G Member 2 (ABCG2) and Ferrochelatase (FECH). Altogether, 258 WHO grade II and 166 WHO grade IV samples were investigated. The mRNA expression levels showed significant differences in 8 of 11 examined genes between WHO grade II and IV gliomas. Significant differences in mRNA expression included increases of HMBS, UROD, FECH and PPOX as well as decreases of SLC15A2, ALAD, UROS and ABCB6 in WHO IV gliomas. Since the majority of changes was found in directions that might actually impair PpIX accumulation in WHO grade IV gliomas, additional studies are needed to analyze the corresponding factors of the heme biosynthesis also on protein level. [ABSTRACT FROM AUTHOR]

Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to the current irradiation of DIPG or DMG: the 5aai regimen. In a series of recent papers, oral 5-ALA was shown to enhance standard therapeutic ionizing irradiation. 5-ALA is currently used in glioblastoma surgery to enable demarcation of overt tumor margins by virtue of selective uptake of 5-ALA by neoplastic cells and selective conversion to protoporphyrin IX (PpIX), which fluoresces after excitation by 410 nm (blue) light. 5-ALA is also useful in treating glioblastomas by virtue of PpIX's transfer of energy to O2 molecules, producing a singlet oxygen that in turn oxidizes intracellular DNA, lipids, and proteins, resulting in selective malignant cell cytotoxicity. This is called photodynamic treatment (PDT). Shallow penetration of light required for PpIX excitation and resultant energy transfer to O2 and cytotoxicity results in the inaccessibility of central structures like the pons or thalamus to sufficient light. The recent demonstration that keV and MeV photons can also excite PpIX and generate singlet O2 allows for reconsideration of 5-ALA PDT for treating DMG and DIPG. 5-ALA has an eminently benign side effect profile in adults and children. A pilot study in DIPG/DMG of slow uptitration of 5-ALA prior to each standard irradiation session—the 5aai regimen—is warranted. [ABSTRACT FROM AUTHOR]

The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its preferential conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently-marketed drugs—the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat—that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial. [ABSTRACT FROM AUTHOR]

Cross-sectional imaging has become a critical aspect in the evaluation of arterial injuries. In particular, angiography using computed tomography (CT) is the imaging of choice. A variety of techniques and options are available when evaluating for arterial injuries. Techniques involve contrast bolus, various phases of contrast enhancement, multiplanar reconstruction, volume rendering, and maximum intensity projection. After the images are rendered, a variety of features may be seen that diagnose the injury. This article provides a general overview of the techniques, important findings, and pitfalls in cross sectional imaging of arterial imaging, particularly in relation to computed tomography. In addition, the future directions of computed tomography, including a few techniques in the process of development, is also discussed. [ABSTRACT FROM AUTHOR]