bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Open Circuit Voltage Relaxation in Lithium-Ion Batteries for the Purpose of State of Charge and State of Health Analysis
Authors: Theuerkauf David , Swan Lukas
Published: July 2022

Open circuit voltage relaxation to a steady state value occurs, and is measured, at the terminals of a lithium-ion battery when current stops flowing. It is of interest for use in determining state of charge and state of health. As voltage relaxation can take several hours, a representative model and curve fitting is necessary for practical usage. Previous studies of lithium-ion voltage relaxation investigate four characteristics: relationship between voltage relaxation magnitude and state of charge; length of relaxation required; model complexity for state of charge estimation; and model complexity for state of health evaluation. However, previous studies have inconsistent methodology or use only one type of lithium-ion cell, making comparison and generalization difficult. To address this, we conducted 3 h and 24 h voltage relaxation experiments over a range of states of charge on three different lithium ion chemistries (nickel cobalt aluminum NCA; nickel manganese cobalt NMC532; lithium iron phosphate LFP) and fitted them with a new voltage relaxation equivalent circuit model. It was found that a 3 h relaxation period was sufficient for NMC and LFP for state of charge and state of health investigations. Voltage relaxation of the NCA cell continued to evolve past 24 h. It was shown that voltage relaxation shape and magnitude changes as a function of state of charge, and the accuracy of estimating state of charge was explored. Strategically choosing a state of charge for state of health assessment can be optimized to accentuate voltage relaxation magnitude and this differs by chemistry. This suggested technique and experimental findings can be paired with battery degradation studies to determine accuracy of assessing state of health.
An Evaluation of Key Adoption Factors towards Using the Fog Technology
Authors: Ali Omar , Shrestha Anup , Jaradat Ashraf , Al-Ahmad Ahmad
Published: July 2022

Fog technology is one of the recent improvements in cloud technology that is designed to reduce some of its drawbacks. Fog technology architecture is often widely distributed to minimize the time required for data processing and enable Internet of Things (IoT) innovations. The purpose of this paper is to evaluate the main factors that might influence the adoption of fog technology. This paper offers a combined framework that addresses fog technology adoption based on the technology adoption perspective, which has been comprehensively researched in the information systems discipline. The proposed integrated framework combines the technology acceptance model (TAM) and diffusion of innovation (DOI) theory to develop a holistic perspective on the adoption of fog technology. The factors that might affect the adoption of fog technology are analyzed from the results of an online survey in 43 different organizations across a wide range of industries. These factors are observed based on data collected from 216 participants, including professional IT staff and senior business executives. This analysis was conducted by using structural equation modeling (SEM). The research results identified nine factors with a statistically significant impact on the adoption of fog technology, and these factors included relative advantage, compatibility, awareness, cost-effectiveness, security, infrastructure, ease of use, usefulness, and location. The findings from this research offer insight to organizations looking to implement fog technology to enable IoT and tap into the digital transformation opportunities presented by this new digital economy.
Chimeric Oncolytic Adenovirus Armed Chemokine Rantes for Treatment of Breast Cancer
Authors: Ang Lin , Li Jiang , Dong Hui , Wang Chunhong , Huang Jin , Li Mingcong , Zhao Min , Su Changqing , Wu Qiang
Published: July 2022

The immunosuppressive state in the tumor microenvironment (TME) of breast cancer makes it difficult to treat with immunotherapy. Oncolytic viruses not only lyse tumor cells but also reshape the TME. Therefore, they can play a multi-mechanism synergistic effect with immunotherapy. In this study, an oncolytic adenovirus Ad5F11bSP-Rantes was constructed and used as a vector to express the chemokine Rantes. The objective of this study was to test the dual mechanisms of the oncolytic effect mediated by virus replication and the enhanced anticancer immune response mediated by Rantes chemotaxis of immune cells. It was found that Ad5F11bSP-Rantes has strong infectivity and effective killing activity against breast cancer cells. In the established triple negative breast cancer (TNBC) xenograft model in NCG mice whose immune system was humanized with human peripheral blood mononuclear cells (PBMCs), Ad5F11bSP-Rantes achieved 88.33% tumor inhibition rate. Rantes expression was high in mouse blood, a large number of CD3+ lymphocytes infiltrated in tumor tissues and E-cadherin was up-regulated in cancer cells, suggesting that Ad5F11bSP-Rantes altered the TME and induced a reversal of cancer cell epithelial–mesenchymal transition (EMT). In conclusion, oncolytic adenovirus can exert the oncolytic effect and the chemotactic effect of immune cells and realize the synergy of multiple anticancer effects. This strategy creates a candidate treatment for the optimization of breast cancer, especially TNBC, combination therapy.
A Fusion Biopsy Framework for Prostate Cancer Based on Deformable Superellipses and nnU-Net
Authors: Altini Nicola , Brunetti Antonio , Napoletano Valeria Pia , Girardi Francesca , Allegretti Emanuela , Hussain Sardar Mehboob , Brunetti Gioacchino , Triggiani Vito , Bevilacqua Vitoantonio , Buongiorno Domenico
Published: July 2022

In prostate cancer, fusion biopsy, which couples magnetic resonance imaging (MRI) with transrectal ultrasound (TRUS), poses the basis for targeted biopsy by allowing the comparison of information coming from both imaging modalities at the same time. Compared with the standard clinical procedure, it provides a less invasive option for the patients and increases the likelihood of sampling cancerous tissue regions for the subsequent pathology analyses. As a prerequisite to image fusion, segmentation must be achieved from both MRI and TRUS domains. The automatic contour delineation of the prostate gland from TRUS images is a challenging task due to several factors including unclear boundaries, speckle noise, and the variety of prostate anatomical shapes. Automatic methodologies, such as those based on deep learning, require a huge quantity of training data to achieve satisfactory results. In this paper, the authors propose a novel optimization formulation to find the best superellipse, a deformable model that can accurately represent the prostate shape. The advantage of the proposed approach is that it does not require extensive annotations, and can be used independently of the specific transducer employed during prostate biopsies. Moreover, in order to show the clinical applicability of the method, this study also presents a module for the automatic segmentation of the prostate gland from MRI, exploiting the nnU-Net framework. Lastly, segmented contours from both imaging domains are fused with a customized registration algorithm in order to create a tool that can help the physician to perform a targeted prostate biopsy by interacting with the graphical user interface.
Gene-Based Therapeutics for Parkinson’s Disease
Authors: Shalaby Karim E. , El-Agnaf Omar M. A.
Published: July 2022

Parkinson’s disease (PD) is a complex multifactorial disorder that is not yet fully surmised, and it is only when such a disease is tackled on multiple levels simultaneously that we should expect to see fruitful results. Gene therapy is a modern medical practice that theoretically and, so far, practically, has demonstrated its capability in joining the battle against PD and other complex disorders on most if not all fronts. This review discusses how gene therapy can efficiently replace current forms of therapy such as drugs, personalized medicine or invasive surgery. Furthermore, we discuss the importance of enhancing delivery techniques to increase the level of transduction and control of gene expression or tissue specificity. Importantly, the results of current trials establish the safety, efficacy and applicability of gene therapy for PD. Gene therapy’s variety of potential in interfering with PD’s pathology by improving basal ganglial circuitry, enhancing dopamine synthesis, delivering neuroprotection or preventing neurodegeneration may one day achieve symptomatic benefit, disease modification and eradication.
Bioactive Cell-Derived ECM Scaffold Forms a Unique Cellular Microenvironment for Lung Tissue Engineering
Authors: Doryab Ali , Schmid Otmar
Published: July 2022

Chronic lung diseases are one of the leading causes of death worldwide. Lung transplantation is currently the only causal therapeutic for lung diseases, which is restricted to end-stage disease and limited by low access to donor lungs. Lung tissue engineering (LTE) is a promising approach to regenerating a replacement for at least a part of the damaged lung tissue. Currently, lung regeneration is limited to a simplified local level (e.g., alveolar–capillary barrier) due to the sophisticated and complex structure and physiology of the lung. Here, we introduce an extracellular matrix (ECM)-integrated scaffold using a cellularization–decellularization–recellularization technique. This ECM-integrated scaffold was developed on our artificial co-polymeric BETA (biphasic elastic thin for air–liquid interface cell culture conditions) scaffold, which were initially populated with human lung fibroblasts (IMR90 cell line), as the main generator of ECM proteins. Due to the interconnected porous structure of the thin (<5 µm) BETA scaffold, the cells can grow on and infiltrate into the scaffold and deposit their own ECM. After a mild decellularization procedure, the ECM proteins remained on the scaffold, which now closely mimicked the cellular microenvironment of pulmonary cells more realistically than the plain artificial scaffolds. We assessed several decellularization methods and found that 20 mM NH4OH and 0.1% Triton X100 with subsequent DNase treatment completely removed the fibroblasts (from the first cellularization) and maintains collagen I and IV as the key ECM proteins on the scaffold. We also showed the repopulation of the primary fibroblast from human (without chronic lung disease (non-CLD) donors) and human bronchial epithelial (16HBE14o−) cells on the ECM-integrated BETA scaffold. With this technique, we developed a biomimetic scaffold that can mimic both the physico-mechanical properties and the native microenvironment of the lung ECM. The results indicate the potential of the presented bioactive scaffold for LTE application.
Differential Effects of D9 Tetrahydrocannabinol (THC)- and Cannabidiol (CBD)-Based Cannabinoid Treatments on Macrophage Immune Function In Vitro and on Gastrointestinal Inflammation in a Murine Model
Authors: Yekhtin Zhanna , Khuja Iman , Meiri David , Or Reuven , Almogi-Hazan Osnat
Published: July 2022

Phytocannabinoids possess a wide range of immune regulatory properties, mediated by the endocannabinoid system. Monocyte/macrophage innate immune cells express endocannabinoid receptors. Dysregulation of macrophage function is involved in the pathogenesis of different inflammatory diseases, including inflammatory bowel disease. In our research, we aimed to evaluate the effects of the phytocannabinoids D9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on macrophage activation. Macrophages from young and aged C57BL/6 mice were activated in vitro in the presence of pure cannabinoids or cannabis extracts. The phenotype of the cells, nitric oxide (NO•) secretion, and cytokine secretion were examined. In addition, these treatments were administered to murine colitis model. The clinical statuses of mice, levels of colon infiltrating macrophages, and inflammatory cytokines in the blood, were evaluated. We demonstrated inhibition of macrophage NO• and cytokine secretion and significant effects on expression of cell surface molecules. In the murine model, clinical scores were improved and macrophage colon infiltration reduced following treatment. We identified higher activity of cannabis extracts as compared with pure cannabinoids. Each treatment had a unique effect on cytokine composition. Overall, our results establish that the effects of cannabinoid treatments differ. A better understanding of the reciprocal relationship between cannabinoids and immunity is essential to design targeted treatment strategies.
Kawasaki Disease-like Vasculitis Facilitates Atherosclerosis, and Statin Shows a Significant Antiatherosclerosis and Anti-Inflammatory Effect in a Kawasaki Disease Model Mouse
Authors: Motoji Yusuke , Fukazawa Ryuji , Matsui Ryosuke , Nagi-Miura Noriko , Miyagi Yasuo , Itoh Yasuhiko , Ishii Yosuke
Published: July 2022

Kawasaki disease (KD) is an acute form of systemic vasculitis that may promote atherosclerosis in adulthood. This study examined the relationships between KD, atherosclerosis, and the long-term effects of HMG-CoA inhibitors (statins). Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally into 5-week-old male apolipoprotein-E-deficient (Apo E-/-) mice to create KD-like vasculitis. Mice were divided into 4 groups: the control, CAWS, CAWS+statin, and late-statin groups. They were sacrificed at 6 or 10 weeks after injection. Statin was started after CAWS injection in all groups except the late-statin group, which was administered statin internally 6 weeks after injection. Lipid plaque lesions on the aorta were evaluated with Oil Red O. The aortic root and abdominal aorta were evaluated with hematoxylin and eosin staining and immunostaining. CAWS vasculitis significantly enhanced aortic atherosclerosis and inflammatory cell invasion into the aortic root and abdominal aorta. Statins significantly inhibited atherosclerosis and inflammatory cell invasion, including macrophages. CAWS vasculitis, a KD-like vasculitis, promoted atherosclerosis in Apo E-/- mice. The long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Therefore, statin treatment may be used for the secondary prevention of cardiovascular events during the chronic phase of KD.
Sanguinarine Induces H2O2-Dependent Apoptosis and Ferroptosis in Human Cervical Cancer
Authors: Alakkal Ameer , Thayyullathil Faisal , Pallichankandy Siraj , Subburayan Karthikeyan , Cheratta Anees Rahman , Galadari Sehamuddin
Published: July 2022

Sanguinarine (SNG) is a benzophenanthridine alkaloid isolated mainly from Sanguinaria canadensis, Chelidonium majus, and Macleaya cordata. SNG is considered an antineoplastic agent based on its cytotoxic activity against various tumors. However, the exact molecular mechanism through which SNG mediates this activity has not been elucidated. Here, we report that SNG induces death in human cervical cancer (HeLa) cells through activation of two interdependent cell death pathways—apoptosis and ferroptosis. SNG-induced apoptosis was characterized by caspase activation and PARP cleavage, while ferroptosis involved solute carrier family 7 member 11 (SLC7A11) down-regulation, glutathione (GSH) depletion, iron accumulation, and lipid peroxidation (LPO). Interestingly, incubation with caspase inhibitor z-VAD-fmk not only inhibited the features of apoptosis, but also negated markers of SNG-induced ferroptosis. Similarly, pretreatment with ferroptosis inhibitor ferrostatin-1 (Fer-1), apart from rescuing cells from SNG-induced ferroptosis, also curbed the features of SNG-induced apoptosis. Our study implies that, together, apoptosis and ferroptosis act as partners in the context of SNG mediated tumor suppression in HeLa cells. Importantly, SNG increased the generation of reactive oxygen species (ROS), and ROS inhibition blocks the induction of both apoptosis and ferroptosis. These findings highlight the value of continued investigation into the potential use of SNG as an antineoplastic agent.
Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients
Authors: Urzì Brancati Valentina , Scarpignato Carmelo , Minutoli Letteria , Pallio Giovanni
Published: July 2022

Immunosuppressant drugs (ISDs) are routinely used in clinical practice to maintain organ transplant survival. However, these drugs are characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability, and a series of severe adverse effects. In particular, genetic factors have been estimated to play a role in this variability because of polymorphisms regarding genes encoding for enzymes and transporters involved in the ISDs pharmacokinetic. Several studies showed important correlations between genetic polymorphisms and ISDs blood levels in transplanted patients; therefore, this review aims to summarize the pharmacogenetics of approved ISDs. We used PubMed database to search papers on pharmacogenetics of ISDs in adults or pediatric patients of any gender and ethnicity receiving immunosuppressive therapy after kidney transplantation. We utilized as search term: “cyclosporine or tacrolimus or mycophenolic acid or sirolimus or everolimus and polymorphism and transplant”. Our data showed that polymorphisms in CYP3A5, CYP3A4, ABCB1, and UGT1A9 genes could modify the pharmacokinetics of immunosuppressants, suggesting that patient genotyping could be a helpful strategy to select the ideal ISDs dose for each patient.
Adalimumab Biosimilar GP2017 versus Adalimumab Originator in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study
Authors: Mocci Giammarco , Bodini Giorgia , Allegretta Leonardo , Cazzato Alessia Immacolata , Chiri Stefania , Aragona Giovanni , Perazzo Patrizia , Ferronato Antonio , Graziani Maria Giovanna , Pagnini Cristiano , Zampaletta Costantino , Graziosi Camilla , Picchio Marcello , Elisei Walter , Maconi Giovanni , Tursi Antonio
Published: July 2022

The approval of adalimumab (ADA) biosimilars for inflammatory bowel disease (IBD) has reduced the cost of treatment. While several ADA biosimilars are currently available, comparative data on the ADA biosimilar GP2017 (HyrimozTM) and its originator (HumiraTM) in IBD are lacking. We compared the efficacy and safety of GP2017 versus originator in IBD outpatients in an Italian real-life setting. This retrospective analysis enrolled consecutive IBD patients with complete clinical, laboratory, and endoscopic data. Clinical activity was assessed with the Mayo score in ulcerative colitis (UC) and the Harvey–Bradshaw Index in Crohn’s disease (CD). The primary endpoints were the induction of remission and the safety of GP2017 versus ADA originator. One hundred and thirty-four patients (30.6% with UC and 69.4% with CD, median age 38 years) were enrolled: 62 (46.3%) patients were treated with GP2017, and 72 (53.7%) with ADA originator; 118 (88.1%) patients were naïve to ADA. Clinical remission was obtained in 105 (78.4%) patients, during a median follow-up of 12 months, 82.3% and 75% in the GP2017 and ADA originator groups, respectively (p = 0.311). Treatment was well tolerated in both groups. This analysis of real-world data suggests that GP2017 and its originator are equivalent in terms of efficacy and safety in patients with IBD.
Aβ and Tau Regulate Microglia Metabolism via Exosomes in Alzheimer’s Disease
Authors: Zhao Yuanxin , Liu Buhan , Wang Jian , Xu Long , Yu Sihang , Fu Jiaying , Yan Xiaoyu , Su Jing
Published: July 2022

One of the most striking hallmarks shared by various neurodegenerative diseases, including Alzheimer’s disease (AD), is microglia-mediated neuroinflammation. The main pathological features of AD are extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles in the brain. Amyloid-β (Aβ) peptide and tau protein are the primary components of the plaques and tangles. The crosstalk between microglia and neurons helps maintain brain homeostasis, and the metabolic phenotype of microglia determines its polarizing phenotype. There are currently many research and development efforts to provide disease-modifying therapies for AD treatment. The main targets are Aβ and tau, but whether there is a causal relationship between neurodegenerative proteins, including Aβ oligomer and tau oligomer, and regulation of microglia metabolism in neuroinflammation is still controversial. Currently, the accumulation of Aβ and tau by exosomes or other means of propagation is proposed as a regulator in neurological disorders, leading to metabolic disorders of microglia that can play a key role in the regulation of immune cells. In this review, we propose that the accumulation of Aβ oligomer and tau oligomer can propagate to adjacent microglia through exosomes and change the neuroinflammatory microenvironment by microglia metabolic reprogramming. Clarifying the relationship between harmful proteins and microglia metabolism will help people to better understand the mechanism of crosstalk between neurons and microglia, and provide new ideas for the development of AD drugs.
Simple Detection of DNA Methyltransferase with an Integrated Padlock Probe
Authors: Wang Yuehua , Han Yingli , Zhou Fangyu , Fan Tingting , Liu Feng
Published: July 2022

DNA methyltransferases (MTases) can be regarded as biomarkers, as demonstrated by many studies on genetic diseases. Many researchers have developed biosensors to detect the activity of DNA MTases, and nucleic acid amplification, which need other probe assistance, is often used to improve the sensitivity of DNA MTases. However, there is no integrated probe that incorporates substrates and template and primer for detecting DNA MTases activity. Herein, we first designed a padlock probe (PP) to detect DNA MTases, which combines target detection with rolling circle amplification (RCA) without purification or other probe assistance. As the substrate of MTase, the PP was methylated and defended against HpaII, lambda exonuclease, and ExoI cleavage, as well as digestion, by adding MTase and the undestroyed PP started RCA. Thus, the fluorescent signal was capable of being rapidly detected after adding SYBRTM Gold to the RCA products. This method has a detection limit of approximately 0.0404 U/mL, and the linear range was 0.5–110 U/mL for M.SssI. Moreover, complex biological environment assays present prospects for possible application in intricacy environments. In addition, the designed detection system can also screen drugs or inhibitors for MTases.
Intrasaccular Flow Disruptor-Assisted Coiling of Intracranial Aneurysms Using the Novel Contour Neurovascular Systems and NEQSTENT: A Single-Center Safety and Feasibility Study
Authors: Diana Francesco , de Dios Lascuevas Marta , Peschillo Simone , Raz Eytan , Yoshimura Shinichi , Requena Ruiz Manuel , Hernández Morales David , Tomasello Alejandro
Published: July 2022

Background: Intrasaccular flow disruptors (IFD) have been introduced in the treatment of intracranial aneurysms (IAs) to overcome the low aneurysm occlusion rate and the high recanalization rate of the coiling technique. Among them, the Contour Neurovascular System (CNS) and the Neqstent (NQS) were designed to reconstruct the aneurysmal neck and both can be used as assisting coiling devices. We aimed to report our preliminary experience with the flow disruptor-assisted coiling (IFD-AC) technique. Methods: We performed a retrospective analysis of prospectively collected data of all patients with IAs treated with the IFD-AC. Results: Between February 2021 and April 2022, we treated 15 IAs with the IFD-AC: 10 ruptured and 5 unruptured. The IFD-AC was successfully performed in 13 cases, with a post-operative RROC 1 in 12 cases (92.3%) and RROC 2 in 1 case (7.7%). There was one ischemic event (6.7%) and no hemorrhagic complications. Twelve patients underwent a mid-term radiologic follow-up: Ten IAs (83.4%) presented an adequate occlusion, while 2 (16.7%) had a recurrence. Conclusions: The IFD-AC, both with the CNS and the NQS, seems a safe technique with promising efficacy profile. The IFD-AC has proved to be safe without antiplatelet therapy in ruptured cases. Further studies are needed to confirm our preliminary results.
Investigation on Forced Convective Heat Transfer at the Building Façade with Louver Blinds under Different Wind Directions
Authors: Ma Rongjiang , Tao Shiwen , Li Zhengrong , Yuan Yanping , Jiang Fujian
Published: July 2022

Exterior louver blinds are one of the most common shading devices attached to the building façade, which will not only screen solar radiation but also affect the flow around the building and change the convective heat exchange at the façade. To better understand how different wind directions affect the convective heat properties of louvered building façades, this paper conducted a CFD simulation with the validation of previous wind-tunnel experiments. A total of 63 shading cases and 7 unshaded cases were both investigated by simulations. It was found that with the increase in wind attack angle θ, the surface-averaged convective heat transfer coefficient (CHTC) at the louvered surface will first increase by about 40~50% (θ from 0° to 60°) and then be cut down by 60% (θ from 60° to 90°). In addition, the convective heat exchange rate at the louver slats will gradually decrease with the growth of θ. Finally, modifications for previous correlations were proposed to quantify the effect of wind directions on the CHTCavg at the blinds and façade, of which the maximum deviation for convective heat exchange rate is less than 18%.
Digital Tools for Revealing and Reducing Carbon Footprint in Infrastructure, Building, and City Scopes
Authors: Yan Jiayi , Lu Qiuchen , Tang Junqing , Chen Long , Hong Jingke , Broyd Tim
Published: July 2022

The climate change issue has been striking and bringing pressure on all countries and industries. The responsibility of the Architecture, Engineering, Construction and Facility Management (AEC/FM) industry is heavy because it accounts for over one-third of global energy use and greenhouse gas emissions. At the same time, the development of digital technology brings the opportunity to mitigate environmental issues. Therefore, this study intended to examine the state-of-the-art of digital development and transformation in the AEC/FM industry by collecting and reviewing the developed digital carbon footprint analysis tools in infrastructure, building, and city scopes. Specifically, this study (1) generated a review methodology for carbon footprint analysis results; (2) demonstrated the review results from the infrastructure, building, and city scopes, analysed and compared the results crossing the scopes from four aspects: carbon footprint analysis strategy, standards and protocols, rating systems, and general development level of digital tools; and (3) discussed the potential directions in the industry to address the environmental issues. This study indicated that the digitalisation level regarding carbon-related areas is still at an early stage, and efforts should be taken both academically and practically to drive the digital development confronting the harsh climate change issue.
Diagnostic Models Combining Clinical Information, Ultrasound and Biochemical Markers for Ovarian Cancer: Cochrane Systematic Review and Meta-Analysis
Authors: Davenport Clare F. , Rai Nirmala , Sharma Pawana , Deeks Jon , Berhane Sarah , Mallett Sue , Saha Pratyusha , Solanki Rita , Bayliss Susan , Snell Kym , Sundar Sudha
Published: July 2022

Background: Ovarian cancer (OC) is a diagnostic challenge, with the majority diagnosed at late stages. Existing systematic reviews of diagnostic models either use inappropriate meta-analytic methods or do not conduct statistical comparisons of models or stratify test performance by menopausal status. Methods: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, CDSR, DARE, Health Technology Assessment Database and SCI Science Citation Index, trials registers, conference proceedings from 1991 to June 2019. Cochrane collaboration review methods included QUADAS-2 quality assessment and meta-analysis using hierarchical modelling. RMI, ROMA or ADNEX at any test positivity threshold were investigated. Histology or clinical follow-up was the reference standard. We excluded screening studies, studies restricted to pregnancy, recurrent or metastatic OC. 2 × 2 diagnostic tables were extracted separately for pre- and post-menopausal women. Results: We included 58 studies (30,121 patients, 9061 cases of ovarian cancer). Prevalence of OC ranged from 16 to 55% in studies. For premenopausal women, ROMA at a threshold of 13.1 (+/−2) and ADNEX at a threshold of 10% demonstrated significantly higher sensitivity compared to RMI I at 200 (p < 0.0001) 77.8 (72.5, 82.4), 94.9 (92.5, 96.6), and 57.1% (50.6 to 63.4) but lower specificity (p < 0.002), 92.5 (90.0, 94.4), 84.3 (81.3, 86.8), and 78.2 (75.8, 80.4). For postmenopausal women, ROMA at a threshold of 27.7 (+/−2) and AdNEX at a threshold of 10% demonstrated significantly higher sensitivity compared to RMI I at a threshold of 200 (p < 0.001) 90.4 (87.4, 92.7), 97.6 (96.2, 98.5), and 78.7 (74.3, 82.5), specificity of ROMA was comparable, whilst ADneX was lower, 85.5 (81.3, 88.9), 81.3 (76.9, 85.0) (p = 0.155), compared to RMI 55.2 (51.2, 59.1) (p < 0.001). Conclusions: In pre-menopausal women, ROMA and ADNEX offer significantly higher sensitivity but significantly decreased specificity. In post-menopausal women, ROMA demonstrates significantly higher sensitivity and comparable specificity to RMI I, ADNEX has the highest sensitivity of all models, but with significantly reduced specificity. RMI I has poor sensitivity compared to ROMA or ADNEX. Choice between ROMA and ADNEX as a replacement test will depend on cost effectiveness and resource implications.
Novel Germline Mutations in a Cohort of Men with Familial Prostate Cancer
Authors: Mondschein Romy , Bolton Damien , Clouston David , Dowty James , Kavanagh Liam , Murphy Declan , Scott Prudence , Taylor Renea A. , Thorne Heather
Published: July 2022

Background: Germline mutations in BRCA2 are associated with aggressive prostate cancer. Additional information regarding the clinical phenotype of germline pathogenic variants in other prostate cancer predisposition genes is required. Clinical testing has been limited by evidence, further restricting knowledge of variants that contribute to prostate cancer development. Objective: Prostate cancer patients who were first- and second-degree relatives from multi-case prostate cancer families underwent a gene panel screen to identify novel (non-BRCA) germline pathogenic variants in cancer predisposition genes and define clinical phenotypes associated with each gene. Methods: The germline genomic DNA (gDNA) of 94 index cases with verified prostate cancer from families with a minimum of two verified prostate cancer cases was screened with an 84-cancer-gene panel. Families were recruited for multi-case breast/ovarian cancer (n = 66), or multi-case prostate cancer (n = 28). Prostate cancer characteristics associated with each gene were compared with prostate cancer cases of confirmed non-mutation carriers (BRCAX), also from multi-case prostate cancer families (n = 111), and with data from the Prostate Cancer Outcomes Registry (PCOR). Results: Ninety-four prostate cancer index cases underwent gene panel testing; twenty-two index cases (22/94; 23%) were found to carry a class 4–5 (C4/5) variant. Six of twenty-two (27%) variants were not clinically notifiable, and seven of twenty-two (31.8%) variants were in BRCA1/2 genes. Nine of twenty-two (40.9%) index cases had variants identified in ATM (n = 4), CHEK2 (n = 2) and HOXB13G84 (n = 3); gDNA for all relatives of these nine cases was screened for the corresponding familial variant. The final cohort comprised 15 confirmed germline mutation carriers with prostate cancer (ATM n = 9, CHEK2 n = 2, HOXB13G84 n = 4). ATM and CHEK2-associated cancers were D’Amico intermediate or high risk, comparable to our previously published BRCA2 and BRCAX prostate cancer cohort. HOXB13G84 carriers demonstrated low- to intermediate-risk prostate cancer. In the BRCAX cohort, 53.2% of subjects demonstrated high-risk disease compared with 25% of the PCOR cohort. Conclusions:ATM and CHEK2 germline mutation carriers and the BRCAX (confirmed non-mutation carriers) cohort demonstrated high risk disease compared with the general population. Targeted genetic testing will help identify men at greater risk of prostate-cancer-specific mortality. Data correlating rare variants with clinical phenotype and familial predisposition will strengthen the clinical validity and utility of these results and establish these variants as significant in prostate cancer detection and management.
Techniques for Profiling the Cellular Immune Response and Their Implications for Interventional Oncology
Authors: Garg Tushar , Weiss Clifford R. , Sheth Rahul A.
Published: July 2022

In recent years there has been increased interest in using the immune contexture of the primary tumors to predict the patient’s prognosis. The tumor microenvironment of patients with cancers consists of different types of lymphocytes, tumor-infiltrating leukocytes, dendritic cells, and others. Different technologies can be used for the evaluation of the tumor microenvironment, all of which require a tissue or cell sample. Image-guided tissue sampling is a cornerstone in the diagnosis, stratification, and longitudinal evaluation of therapeutic efficacy for cancer patients receiving immunotherapies. Therefore, interventional radiologists (IRs) play an essential role in the evaluation of patients treated with systemically administered immunotherapies. This review provides a detailed description of different technologies used for immune assessment and analysis of the data collected from the use of these technologies. The detailed approach provided herein is intended to provide the reader with the knowledge necessary to not only interpret studies containing such data but also design and apply these tools for clinical practice and future research studies.
The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas
Authors: Ramchatesingh Brandon , Gantchev Jennifer , Martínez Villarreal Amelia , Gill Raman Preet Kaur , Lambert Marine , Sivachandran Sriraam , Lefrançois Philippe , Litvinov Ivan V.
Published: July 2022

Keratinocyte carcinomas are among the most prevalent malignancies worldwide. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the two cancers recognized as keratinocyte carcinomas. The standard of care for treating these cancers includes surgery and ablative therapies. However, in recent years, targeted therapies (e.g., cetuximab for cSCC and vismodegib/sonidegib for BCC) have been used to treat advanced disease as well as immunotherapy (e.g., cemiplimab). These treatments are expensive and have significant toxicities with objective response rates approaching ~50–65%. Hence, there is a need to dissect the molecular pathogenesis of these cancers to identify novel biomarkers and therapeutic targets to improve disease management. Several cancer-testis antigens (CTA) and developmental genes (including embryonic stem cell factors and fetal genes) are ectopically expressed in BCC and cSCC. When ectopically expressed in malignant tissues, functions of these genes may be recaptured to promote tumorigenesis. CTAs and developmental genes are emerging as important players in the pathogenesis of BCC and cSCC, positioning themselves as attractive candidate biomarkers and therapeutic targets requiring rigorous testing. Herein, we review the current research and offer perspectives on the contributions of CTAs and developmental genes to the pathogenesis of keratinocyte carcinomas.
Serial Analysis of Gene Mutations and Gene Expression during First-Line Chemotherapy against Metastatic Colorectal Cancer: Identification of Potentially Actionable Targets within the Multicenter Prospective Biomarker Study REVEAL
Authors: Kumbrink Jörg , Bohlmann Lisa , Mamlouk Soulafa , Redmer Torben , Peilstöcker Daniela , Li Pan , Lorenzen Sylvie , Algül Hana , Kasper Stefan , Hempel Dirk , Kaiser Florian , Michl Marlies , Bartsch Harald , Neumann Jens , Klauschen Frederick , von Bergwelt-Baildon Michael , Modest Dominik , Stahler Arndt , Stintzing Sebastian , Jung Andreas , Kirchner Thomas , Schäfer Reinhold , Heinemann Volker , Holch Julian
Published: July 2022

Most metastatic colorectal cancer (mCRC) patients succumb to refractory disease due to secondary chemotherapy resistance. To elucidate the molecular changes associated with secondary resistance, we recruited 64 patients with mCRC and hepatic metastases before standard first-line chemotherapy between 2014 and 2018. We subjected DNA from primary tumor specimens (P), hepatic metastasis specimens after treatment (M), and liquid biopsies (L) taken prior to (pre), during (intra), and after (post) treatment to next generation sequencing. We performed Nanostring expression analysis in P and M specimens. Comparative bioinformatics and statistical analysis revealed typical mutational patterns with frequent alterations in TP53, APC, and KRAS in P specimens (n = 48). P and pre-L (n = 42), as well as matched P and M (n = 30), displayed a similar mutation spectrum. In contrast, gene expression profiles classified P (n = 31) and M (n = 23), distinguishable by up-regulation of immune/cytokine receptor and autophagy programs. Switching of consensus molecular subtypes from P to M occurred in 58.3% of cases. M signature genes SFRP2 and SPP1 associated with inferior survival, as validated in an independent cohort. Molecular changes during first-line treatment were detectable by expression profiling rather than by mutational tumor and liquid biopsy analyses. SFRP2 and SPP1 may serve as biomarkers and/or actionable targets.
Variation in Treatment Patterns of Patients with Early-Onset Gastric Cancer
Authors: LaPelusa Michael , Shen Chan , Gillaspie Erin A. , Cann Christopher , Lambright Eric , Chakravarthy A. Bapsi , Gibson Michael K. , Eng Cathy
Published: July 2022

Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate burden of EOGC and what factors influence how patients with EOGC are treated. Methods: We conducted a retrospective, population-based study of patients diagnosed with gastric cancer from 2004 to 2018 using the National Cancer Database (NCDB). In addition to identifying unique demographic characteristics of patients with EOGC, we evaluated (using multivariable logistic regression controlling for year of diagnoses, primary site, and stage) how gender/sex, race/ethnicity, treatment facility type, payor status, and location of residence influenced the receipt of surgery, chemotherapy, and radiation. Results: Compared to patients 45–70 and >70 years of age with gastric cancer, patients with EOGC were more likely to be female, Asian/Pacific Islander (PI), African American (AA), Hispanic, uninsured, and present with stage IV disease. On multivariable analysis, several differences among subsets of patients with EOGC were identified. Female patients with EOGC were less likely to receive surgery and chemotherapy than male patients with EOGC. Asian/Pacific Islander patients with EOGC were more likely to receive chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. African American patients were more likely to receive chemotherapy than Caucasian patients with EOGC. Hispanic patients were more likely to receive surgery and chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. Patients with EOGC treated at community cancer centers were more likely to receive surgery and less likely to receive chemotherapy than patients with EOGC treated at academic centers. Uninsured patients with EOGC were more likely to receive surgery and less likely to receive chemotherapy than privately insured patients with EOGC. Patients with EOGC living in locations not adjacent to metropolitan areas were less likely to receive surgery compared to patients with EOGC who resided in metropolitan areas, Conclusions: Patients with EOGC are a demographically distinct population. Treatment of these patients varies significantly based on several demographic factors. Additional analysis is needed to elucidate why particular groups are more affected by EOGC and how treatment decisions are made for, and by, these patients.
Efficient Prediction of Ki-67 Proliferation Index in Meningiomas on MRI: From Traditional Radiological Findings to a Machine Learning Approach
Authors: Zhao Yanjie , Xu Jianfeng , Chen Boran , Cao Le , Chen Chaoyue
Published: July 2022

Background/aim This study aimed to explore the value of radiological and radiomic features retrieved from magnetic resonance imaging in the prediction of a Ki-67 proliferative index in meningioma patients using a machine learning model. Methods This multicenter, retrospective study included 371 patients collected from two centers. The Ki-67 expression was classified into low-expressed and high-expressed groups with a threshold of 5%. Clinical features and radiological features were collected and analyzed by using univariate and multivariate statistical analyses. Radiomic features were extracted from contrast-enhanced images, followed by three independent feature selections. Six predictive models were constructed with different combinations of features by using linear discriminant analysis (LDA) classifier. Results The multivariate analysis suggested that the presence of intratumoral necrosis (p = 0.032) and maximum diameter (p < 0.001) were independently correlated with a high Ki-67 status. The predictive models showed good performance with AUC of 0.837, accuracy of 0.810, sensitivity of 0.857, and specificity of 0.771 in the internal test and with AUC of 0.700, accuracy of 0.557, sensitivity of 0.314, and specificity of 0.885 in the external test. Conclusion The results of this study suggest that the predictive model can efficiently predict the Ki-67 index of meningioma patients to facilitate the therapeutic management.
The Long and Winding Road: An Overview of the Immunological Landscape of Intracranial Meningiomas
Authors: Giammalva Giuseppe Roberto , Brunasso Lara , Paolini Federica , Costanzo Roberta , Bonosi Lapo , Benigno Umberto Emanuele , Ferini Gianluca , Sava Serena , Colarossi Cristina , Umana Giuseppe Emmanuele , Gerardi Rosa Maria , Sturiale Carmelo Lucio , Albanese Alessio , Iacopino Domenico Gerardo , Maugeri Rosario
Published: July 2022

The role of immunotherapy is gaining ever-increasing interest in the neuro-oncological field, and this is also expanding to the management of intracranial meningioma. Meningiomas are still the most common primary adult tumor of the CNS, and even though surgery and/or radiotherapy still represent cornerstones of their treatment, recent findings strongly support the potential role of specific immune infiltrate cells, their features and genomics, for the application of personalized treatments and prognostic implications. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a descriptive and complete overview about the characteristics, role and potential implications of immunology in meningioma tumors. Seventy articles were included and analyzed in the present paper. The meningioma microenvironment reveals complex immune tumor-immune cells interactions that may definitely influence tumor progression, as well as offering unexpected opportunities for treatment.
On the Optimization of Ni/A and Ni/X Synthesis Procedure toward Active and Selective Catalysts for the Production of CH4 from CO2
Authors: Krachuamram Somkiat , Kidkhunthod Pinit , Poo-arporn Yingyot , Kamonsutthipaijit Nuntaporn , Chanapattharapol Kingkaew Chayakul
Published: July 2022

Herein, optimization of zeolite NaA/NaX synthesis conditions in order to obtain the final product with high surface area and pore volume was investigated. An optimal synthesis condition was 5 days aging time and crystallization time of 9 h with the co-addition of cetyltrimethylammonium bromide (CTAB) and heptane. All those optimal synthesis conditions provided mixed phase between zeolite NaA and NaX, and addition of those organic phases improved the surface area and pore volume of the final synthesized zeolite. The role of CTAB and heptane on increasing the surface area of zeolite was studied by in situ small-angle X-ray scattering (SAXS). The SAXS results evidenced that small nucleation precursor was formed upon the addition of organic phase, and this nucleation precursor can provide zeolite with high-characteristic XRD signals of mixed phase of zeolite A and X after the crystallization process. The synthesized zeolite obtained from optimal synthesis condition with high surface area was further used as a catalyst support by impregnating with 5, 10, 15, and 20wt%Ni for catalyzing CO2 methanation reaction. The results found that 15wt%Ni/zeolite expressed the highest catalytic activity with high CH4 selectivity and stability. This was due to high dispersion of Ni species on catalyst surface and high metal-support interaction between Ni and zeolite. These results indicated that the mixed phase zeolite support can be a potential catalyst support for this reaction.
Acid-Modified Clays for the Catalytic Obtention of 5-Hydroxymethylfurfural from Glucose
Authors: Sánchez Vladimir , González María Dolores , Salagre Pilar , Cesteros Yolanda
Published: July 2022

5-hydroxymethylfurfural (5-HMF) is an important platform molecule for the synthesis of high-added value products. Several synthesized clay materials, such as mesoporous hectorite and fluorohectorite, in addition to commercial montmorillonite K-10, have been acid modified by different methodologies to be applied as catalysts for the obtention of 5-HMF from glucose. The effects of the Brønsted and/or Lewis acidity, the reaction temperature and time, and the catalyst/glucose ratio on the conversion but especially on the selectivity to 5-HMF have been studied. By comparing the synthesized clays, the best selectivity to 5-HMF (36%) was obtained at 140 °C for 4 h with H-fluorohectorite because of the presence of strong Brønsted acid sites, although its conversion was the lowest (33%) due to its low amounts of Lewis acid sites. Different strategies, such as physical mixtures of montmorillonite K10, which contains high amounts of Lewis acid centers, with Amberlyst-15, which has high amounts of Brønsted acid sites, or the incorporation of rhenium compounds, were carried out. The best selectivity to 5-HMF (62%) was achieved with a mixture of 44 wt % Amberlyst-15 and 56 wt % of montmorillonite K10 for a 56% of conversion at 140 °C for 4 h. This proportion optimized the amount of Brønsted and Lewis acid sites in the catalyst under these reaction conditions.
Synthesis of Glycoluril Dimers with the Ability to Form Polymeric Self-Associates in Water
Authors: Sokolov Jan , Šindelář Vladimír
Published: July 2022

Supramolecular self-assembly in water resulting in polymeric structures is emerging because of its potential in the preparation of adaptive materials with applications in biology and medicine. Here, we report the first example of host molecules based on glycoluril dimers, which self-associate into linear oligomers in water. The degree of polymerization for the resulting supramolecular aggregates was calculated using the isodesmic model and the Carothers equation. The model compound was prepared to enable a deeper understanding of the forces responsible for the self-association of the glycoluril dimer-based monomers in water.