bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Needle Type, Number of Layers on FPAFC Composite against Low-Velocity Projectile Impact
Authors: Prasad Nandhu , Murali Gunasekaran , Abid Sallal R. , Vatin Nikolai , Fediuk Roman , Amran Mugahed
Published: December 2021

Protective structures subjected to intensive loads that may benefit from the use of multilayer composite structures with excellent hardness and impact resistance represent an emerging research field in recent times. In this study, low-velocity projectile impact tests were performed on Functionally-graded Preplaced Aggregate Fibrous Concrete (FPAFC) mixtures to evaluate their performance. The effects of projectile needle type, fibre type and hybridization in addition to the number of layers in the composites on projectile impact were investigated. The bioinspiration of the excellent impact strength of turtle shells was used to design an FPAFC comprising a higher amount of steel and polypropylene fibres at the outer layers. In parallel, one and two-layered concretes were also cast to assess the effectiveness of three-layered FPAFC. The tests were performed on disc specimens using non-deformable compound bevel, convex edge and hollow edge projectiles. The damage severity was quantified by the top damage area, bottom damage area and depth of penetration. In addition, a simple analytical model for predicting the composite mass expulsion was developed and implemented. Findings indicated that regardless of fiber type and distribution, the compound bevel projectile needle produced the lowest impact numbers for all single, double and triple-layer specimens compared to the convex edge and hollow edge projectiles. Repeated projectile impacts increased the penetration depth and damaged area at the top and bottom surfaces of all targets. Targets were more resistant to convex edge and hollow edge projectile penetration than the compound bevel. The experimental and analytical model results for mass expelled from the top surface are reasonably acceptable. This research gives an idea of developing advanced fibrous composite with superior impact resistance for the promising protective structures.
A New Response Surface Stochastic Analysis Method for Spatial Structure Stability—The Reticulated Shell Structure as an Example
Authors: Liu Huijuan , Tondini Nicola , Lu Xisen , Chen Chunxiang , Xu Zhonggen
Published: December 2021

For a long time, spatial structures have been widely used. However, compared with the high strength of their material, their stability is weak, and especially sensitive to damage and defects. This feature has increased the engineering industry’s high requirements for their stability analysis. As we all know, this problem is more prominent for the reticulated shell structure, which is a classic representative of the spatial structure. However, in the current analysis methods for the stability of reticulated shells, the deterministic analysis method cannot consider the random characteristics of defects. Other random methods, such as the random defect modal method, and many improved methods, require more samples and calculation time. This unfavorable situation makes its engineering application greatly restricted. In addition, the random modal superposition method and derivation method based on Monte Carlo has not fundamentally changed this limitation. In order to fundamentally overcome this traditional shortcoming, this paper comprehensively studies the advantages of the high accuracy of the random defect modal method and the improved method, and at the same time, investigates the speed advantage of the response surface method, and then creates a new stochastic analysis method based on the response surface method. Finally, the analysis results of the calculation examples in this paper prove that it successfully balances and satisfies the dual requirements of accuracy and speed required for calculating the stability of the reticulated shell structure. Moreover, it has universal applicability to different forms of reticulated shells, such as classic 6-point flat domes, traditional reticulated shell structures, and bionic reticulated shell structures, and even other types of spatial structures.
Adoption of Blockchain Technology through Digital Twins in the Construction Industry 4.0: A PESTELS Approach
Authors: Teisserenc Benjamin , Sepasgozar Samad
Published: December 2021

The key challenges of the building, engineering, construction, operations, and mining (BECOM) industries are the lack of trust, inefficiencies, and the fragmentation of the information value chain into vulnerable data silos throughout the lifecycle of projects. This paper aims to develop a novel conceptual model for the implementation of blockchain technology (BCT) for digital twin(s) (DT) in the BECOM industry 4.0 to improve trust, cyber security, efficiencies, information management, information sharing, and sustainability. A PESTELS approach is used to review the literature and identify the key challenges affecting BCT adoption for the BECOM industry 4.0. A review of the technical literature on BCT combined with the findings from PESTELS analysis permitted researchers to identify the key technological factors affecting BCT adoption in the industry. This allowed offering a technological framework—namely, the decentralized digital twin cycle (DDTC)—that leverages BCT to address the key technological factors and to ultimately enhance trust, security, decentralization, efficiency, traceability, and transparency of information throughout projects’ lifecycles. The study also identifies the gaps in the integration of BCT with key technologies of industry 4.0, including the internet of things (IoT), building information modeling (BIM), and DT. The framework offered addresses key technological factors and narrows key gaps around network governance, scalability, decentralization, interoperability, energy efficiency, computational requirements, and BCT integration with IoT, BIM, and DT throughout projects’ lifecycles. The model also considers the regulatory aspect and the environmental aspect, and the circular economy (CE). The theoretical framework provides key technological building blocks for industry practitioners to develop the DDTC concept further and implement it through experimental works. Finally, the paper provides an industry-specific analysis and technological approach facilitating BCT adoption through DT to address the key challenges and improve sustainability for the BECOM industry 4.0.
Epilepsy in NF1: Epidemiologic, Genetic, and Clinical Features. A Monocentric Retrospective Study in a Cohort of 784 Patients
Authors: Sorrentino Ugo , Bellonzi Silvia , Mozzato Chiara , Brasson Valeria , Toldo Irene , Parrozzani Raffaele , Clementi Maurizio , Cassina Matteo , Trevisson Eva
Published: December 2021

An increased lifetime risk of epilepsy has been reported in neurofibromatosis type 1 (NF1) patients, ranging between 4% and 14%. To further analyze the correlation between NF1 and epilepsy, we retrospectively reviewed the epidemiologic, clinical, radiological, and molecular data of 784 unselected patients diagnosed with NF1 and referred to the neurofibromatosis outpatient clinics at the University Hospital of Padua. A crude prevalence of epilepsy of 4.7% was observed. In about 70% of cases, seizures arose in the context of neuroradiological findings, with the main predisposing factors being cerebral vasculopathies and hydrocephalus. In the absence of structural abnormalities, the prevalence of epilepsy was found to be 1.27%, which is approximately equal to the total prevalence in the general population. NF1 patients with seizures exhibit a higher incidence of intellectual disability and/or developmental delay, as well as of isolated learning disabilities. The comparison of causative NF1 mutations between the two groups did not reveal a specific genotype–phenotype correlation. Our data refine the current knowledge on epileptological manifestations in NF1 patients, arguing against the hypothesis that specific mechanisms, inherent to neurofibromin cellular function, might determine an increased risk of epilepsy in this condition.
New Trends in the Detection of Gynecological Precancerous Lesions and Early-Stage Cancers
Authors: Holcakova Jitka , Bartosik Martin , Anton Milan , Minar Lubos , Hausnerova Jitka , Bednarikova Marketa , Weinberger Vit , Hrstka Roman
Published: December 2021

The prevention and early diagnostics of precancerous stages are key aspects of contemporary oncology. In cervical cancer, well-organized screening and vaccination programs, especially in developed countries, are responsible for the dramatic decline of invasive cancer incidence and mortality. Cytological screening has a long and successful history, and the ongoing implementation of HPV triage with increased sensitivity can further decrease mortality. On the other hand, endometrial and ovarian cancers are characterized by a poor accessibility to specimen collection, which represents a major complication for early diagnostics. Therefore, despite relatively promising data from evaluating the combined effects of genetic variants, population screening does not exist, and the implementation of new biomarkers is, thus, necessary. The introduction of various circulating biomarkers is of potential interest due to the considerable heterogeneity of cancer, as highlighted in this review, which focuses exclusively on the most common tumors of the genital tract, namely, cervical, endometrial, and ovarian cancers. However, it is clearly shown that these malignancies represent different entities that evolve in different ways, and it is therefore necessary to use different methods for their diagnosis and treatment.
The Roles of Tricellular Tight Junction Protein Angulin-1/Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Endometriosis and Endometrioid-Endometrial Carcinoma
Authors: Shimada Hiroshi , Kohno Takayuki , Konno Takumi , Okada Tadahi , Saito Kimihito , Shindo Yuma , Kikuchi Shin , Tsujiwaki Mitsuhiro , Ogawa Marie , Matsuura Motoki , Saito Tsuyoshi , Kojima Takashi
Published: December 2021

Tight junction proteins play roles beyond permeability barriers functions and control cell proliferation and differentiation. The relation between tight junctions and the signal transduction pathways affects cell growth, invasion and migration. Abnormality of tight junction proteins closely contributes to epithelial mesenchymal transition (EMT) and malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) forms tricellular contacts that has a barrier function. Downregulation of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). These alterations have been shown to link to not only multiple signaling pathways such as Hippo/YAP, HDAC, AMPK, but also cell metabolism in ECC cell line Sawano. Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis stimulating p53 protein 2 (ASPP2) downregulates angulin-1/LSR. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome in cytokinesis. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how downregulation of angulin-1/LSR promotes development of endometriosis and EEC and discusses about the roles of angulin-1/LSR and its related proteins, including claudins and ASPP2.
Prognostic Impact of Sarcopenia in Patients with Metastatic Hormone-Sensitive Prostate Cancer
Authors: Lee Ji Hyun , Jee Byul A , Kim Jae-Hun , Bae Hoyoung , Chung Jae Hoon , Song Wan , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Lee Hyun Moo , Park Se Hoon , Kang Minyong
Published: December 2021

The clinical value of sarcopenia has not been determined yet in metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively evaluated data of 70 consecutive patients with mHSPC receiving treatment with either early docetaxel (n = 42) or abiraterone acetate (n = 28) between July 2018 and April 2021. Skeletal muscle index was calculated from cross-sectional areas of skeletal muscle on baseline computed tomography (CT), defining sarcopenia as a skeletal muscle index of ≤52.4 cm2/m2. Failure-free survival (FFS), radiographic progression-free survival, and time to prostate-specific antigen (PSA) progression were estimated using the Kaplan–Meier method, and differences in survival probability were compared using the log-rank test. Cox proportional hazards regression analysis was conducted to identify the predictors of clinical outcomes. Patients with sarcopenia (n = 47) had shorter FFS than those without sarcopenia (n = 23) (median, 20.1 months vs. not reached; log-rank p < 0.001). Sarcopenia was independently associated with shorter FFS (hazard ratio (HR), 6.69; 95% confidence interval (CI), 1.57–28.49; p = 0.010) and time to PSA progression (HR, 12.91; 95% CI, 1.08–153.85; p = 0.043). In conclusion, sarcopenia is an independent prognostic factor for poor FFS and time to PSA progression in patients with mHSPC who receive early docetaxel or abiraterone acetate treatment.
Side-by-Side Comparison of Five Chelators for 89Zr-Labeling of Biomolecules: Investigation of Chemical/Radiochemical Properties and Complex Stability
Authors: Damerow Helen , Hübner Ralph , Judmann Benedikt , Schirrmacher Ralf , Wängler Björn , Fricker Gert , Wängler Carmen
Published: December 2021

In this work, five different chelating agents, namely DFO, CTH-36, DFO*, 3,4,3-(LI-1,2-HOPO) and DOTA-GA, were compared with regard to the relative kinetic inertness of their corresponding 89Zr complexes to evaluate their potential for in vivo application and stable 89Zr complexation. The chelators were identically functionalized with tetrazines, enabling a fully comparable, efficient, chemoselective and biorthogonal conjugation chemistry for the modification of any complementarily derivatized biomolecules of interest. A small model peptide of clinical relevance (TCO-c(RGDfK)) was derivatized via iEDDA click reaction with the developed chelating agents (TCO = trans-cyclooctene and iEDDA = inverse electron demand Diels-Alder). The bioconjugates were labeled with 89Zr4+, and their radiochemical properties (labeling conditions and efficiency), logD(7.4), as well as the relative kinetic inertness of the formed complexes, were compared. Furthermore, density functional theory (DFT) calculations were conducted to identify potential influences of chelator modification on complex formation and geometry. The results of the DFT studies showed—apart from the DOTA-GA derivative—no significant influence of chelator backbone functionalization or the conjugation of the chelator tetrazines by iEDDA. All tetrazines could be efficiently introduced into c(RGDfK), demonstrating the high suitability of the agents for efficient and chemoselective bioconjugation. The DFO-, CTH-36- and DFO*-modified c(RGDfK) peptides showed a high radiolabeling efficiency under mild reaction conditions and complete 89Zr incorporation within 1 h, yielding the 89Zr-labeled analogs as homogenous products. In contrast, 3,4,3-(LI-1,2-HOPO)-c(RGDfK) required considerably prolonged reaction times of 5 h for complete radiometal incorporation and yielded several different 89Zr-labeled species. The labeling of the DOTA-GA-modified peptide was not successful at all. Compared to [89Zr]Zr-DFO-, [89Zr]Zr-CTH-36- and [89Zr]Zr-DFO*-c(RGDfK), the corresponding [89Zr]Zr-3,4,3-(LI-1,2-HOPO) peptide showed a strongly increased lipophilicity. Finally, the relative stability of the 89Zr complexes against the EDTA challenge was investigated. The [89Zr]Zr-DFO complex showed—as expected—a low kinetic inertness. Unexpectedly, also, the [89Zr]Zr-CTH-36 complex demonstrated a high susceptibility against the challenge, limiting the usefulness of CTH-36 for stable 89Zr complexation. Only the [89Zr]Zr-DFO* and the [89Zr]Zr-3,4,3-(LI-1,2-HOPO) complexes demonstrated a high inertness, qualifying them for further comparative in vivo investigation to determine the most appropriate alternative to DFO for clinical application.
Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers
Authors: Yoshida Hiroshi , Shiraishi Kouya , Kato Tomoyasu
Published: December 2021

Cervical cancer is the fourth most common cancer in women worldwide and is predominantly caused by infection with human papillomavirus (HPV). However, a small subset of cervical cancers tests negative for HPV, including true HPV-independent cancers and false-negative cases. True HPV-negative cancers appear to be more prevalent in certain pathological adenocarcinoma subtypes, such as gastric- and clear-cell-type adenocarcinomas. Moreover, HPV-negative cervical cancers have proven to be a biologically distinct tumor subset that follows a different pathogenetic pathway to HPV-associated cervical cancers. HPV-negative cervical cancers are often diagnosed at an advanced stage with a poor prognosis and are expected to persist in the post-HPV vaccination era; therefore, it is important to understand HPV-negative cancers. In this review, we provide a concise overview of the molecular pathology of HPV-negative cervical cancers, with a focus on their definitions, the potential causes of false-negative HPV tests, and the histology, genetic profiles, and pathogenesis of HPV-negative cancers.
Impact of Sarcopenia and Inflammation on Patients with Advanced Non-Small Cell Lung Cancer (NCSCL) Treated with Immune Checkpoint Inhibitors (ICIs): A Prospective Study
Authors: Tenuta Marta , Gelibter Alain , Pandozzi Carla , Sirgiovanni Grazia , Campolo Federica , Venneri Mary Anna , Caponnetto Salvatore , Cortesi Enrico , Marchetti Paolo , Isidori Andrea M. , Sbardella Emilia
Published: December 2021

Background: Sarcopenia is a condition characterized by loss of skeletal muscle mass associated with worse clinical outcomes in cancer patients. Data on sarcopenia in patients undergoing immune checkpoint inhibitors (ICI) therapy are still limited. The aim of this prospective observational study was to investigate the relationship between sarcopenia, ICI treatment response and immunological profile, in patients with advanced non-small cell lung cancer (NSCLC). Methods: Forty-seven stage IV NSCLC patient candidates for starting ICI, were enrolled from the Policlinico Umberto I outpatient Oncology. Patients underwent baseline blood test, inflammatory markers, cytokine assessment and body composition with dual-energy X-ray absorptiometry (DXA). Sarcopenia was defined with appendicular skeletal muscle mass over height2 (ASM/heigh2). Results: Overall, 19/47 patients (40.4%) results were sarcopenic. Sarcopenic patients showed significantly shorter PFS than non-sarcopenic ones (20.3 weeks, 95% CI 7.5–33.1 vs. 61 weeks, 95% CI 22.5–99.4, p = 0.047). Specifically, they had an 8.1 times higher risk of progression disease (PD) than non-sarcopenic patients (OR 8.1, 95%, p = 0.011). Conclusions: Sarcopenic patients showed worse PFS and had a higher risk of PD compared to non-sarcopenic ones. Therefore, sarcopenia may reflect the increased metabolic activity of more aggressive tumors, which involves systemic inflammation and muscle wasting and could be considered a negative predictive factor for ICI response.
Dosimetric Comparisons between Proton Beam Therapy and Modern Photon Radiation Techniques for Stage I Non-Small Cell Lung Cancer According to Tumor Location
Authors: Bayasgalan Unurjargal , Moon Sung Ho , Kim Tae Hyun , Kim Tae Yoon , Lee Seung Hyun , Suh Yang-Gun
Published: December 2021

Herein, we investigated the dosimetric benefits for proton beam therapy (PBT) over modern photon radiation techniques according to tumor location (central, peripheral, and close to the chest wall) for stage I non-small cell lung cancer (NSCLC) patients. A total of 42 patients with stage I NSCLC were treated with PBT with a total dose of 50–70 Gy in four or 10 fractions considering the risk of treatment-related toxicities. Simulation plans for three-dimensional conformal radiation therapy (3D-CRT), static-field intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT) were retrospectively generated using the same treatment volumes as implemented in the PBT plans for these patients. Dosimetric improvements were observed with PBT as compared with all the photon-based radiation techniques with regards to the mean lung dose, lung V5 and V10, mean heart dose, and heart V5 and V10 in all locations. Moreover, lower radiation exposure to the chest wall was observed within PBT for peripherally located and close to the chest wall tumors. All radiotherapy modalities achieved clinically satisfactory treatment plans in the current study. Notably, the usage of PBT resulted in significant dosimetric improvements in the lung and heart over photon-based techniques at all tumor locations, including the periphery, for stage I NSCLC.
Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management
Authors: Beddok Arnaud , Cottu Paul , Fourquet Alain , Kirova Youlia
Published: December 2021

Background: The objective of the present study was to review the essential knowledge about the combinations of the most commonly used or under development targeted treatments and radiation therapy (RT). Methods: Preclinical and clinical studies investigating this combination were extensively reviewed. Results: Several studies showed that the combination of RT and tamoxifen increased the risk of radiation-induced pulmonary toxicity; therefore, both modalities should not be given concomitantly. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and RT seems to be safe. However, trastuzumab emtansine (T-DM1) should not be administered concurrently with brain RT since this combination could increase the risk of brain radionecrosis. The combination of RT and other new target treatments such as selective estrogen receptor degradants, lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but was essentially evaluated on retrospective or prospective studies with a small number of patients. Furthermore, there is considerable heterogeneity among these studies regarding the dose and fractionation of radiation, the dosage of drugs, and the sequence of treatments used. Conclusions: The combination of RT with most targeted therapies for BC appears to be well-tolerated, but these results need to be confirmed in prospective randomized studies.
β-Hydroxy-β-Methylbutyrate Supplementation Promotes Antitumor Immunity in an Obesity Responsive Mouse Model of Pancreatic Ductal Adenocarcinoma
Authors: Coleman Michael F. , Liu Kristyn A. , Pfeil Alexander J. , Etigunta Suhas K. , Tang Xiaohu , Fabela Salvador , Lashinger Laura M. , Cui Zhengrong , Hursting Stephen D.
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the United States, and effective therapies for PDAC are currently lacking. Moreover, PDAC is promoted and exacerbated by obesity, while cachexia and sarcopenia are exceptionally common comorbidities that predict both poor survival and treatment response. Managing PDAC with immunotherapies has thus far proven ineffective, partly due to the metabolically hostile tumor microenvironment. β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine commonly used as a dietary supplement to boost muscle growth and immune function, may be an attractive candidate to augment PDAC therapy. We therefore sought to test the hypothesis that HMB would enhance antitumor immunity while protecting mouse muscle mass. Control and diet-induced obese C57BL/6 male mice bearing subcutaneously injected Panc02 tumors were supplemented with 1% HMB and treated with or without 50 mg/kg gemcitabine (n = 15/group). HMB was associated with reduced muscle inflammation and increased muscle fiber size. HMB also reduced tumor growth and promoted antitumor immunity in obese, but not lean, mice, independent of the gemcitabine treatment. Separately, in lean tumor-bearing mice, HMB supplementation promoted an anti-PD1 immunotherapy response (n = 15/group). Digital cytometry implicated the decreased abundance of M2-like macrophages in PDAC tumors, an effect that was enhanced by anti-PD1 immunotherapy. We confirmed that HMB augments M1-like macrophage (antitumor) polarization. These preclinical findings suggest that HMB has muscle-sparing and antitumor activities against PDAC in the context of obesity, and that it may sensitize otherwise nonresponsive PDAC to immunotherapy.
Predictive Biomarkers for Outcomes of Immune Checkpoint Inhibitors (ICIs) in Melanoma: A Systematic Review
Authors: Baltussen Joosje C. , Welters Marij J. P. , Verdegaal Elizabeth M. E. , Kapiteijn Ellen , Schrader Anne M. R. , Slingerland Marije , Liefers Gerrit-Jan , van der Burg Sjoerd H. , Portielje Johanneke E. A. , de Glas Nienke A.
Published: December 2021

Immune checkpoint inhibitors (ICIs) have strongly improved the survival of melanoma patients. However, as durable response to ICIs are only seen in a minority, there is an unmet need to identify biomarkers that predict response. Therefore, we provide a systematic review that evaluates all biomarkers studied in association with outcomes of melanoma patients receiving ICIs. We searched Pubmed, COCHRANE Library, Embase, Emcare, and Web of Science for relevant articles that were published before June 2020 and studied blood, tumor, or fecal biomarkers that predicted response or survival in melanoma patients treated with ICIs. Of the 2536 identified reports, 177 were included in our review. Risk of bias was high in 40%, moderate in 50% and low in 10% of all studies. Biomarkers that correlated with response were myeloid-derived suppressor cells (MDSCs), circulating tumor cells (CTCs), CD8+ memory T-cells, T-cell receptor (TCR) diversity, tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), and a favorable gut microbiome. This review shows that biomarkers for ICIs in melanoma patients are widely studied, but heterogeneity between studies is high, average sample sizes are low, and validation is often lacking. Future studies are needed to further investigate the predictive utility of some promising candidate biomarkers.
Liver-Directed Therapy for Neuroendocrine Metastases: From Interventional Radiology to Nuclear Medicine Procedures
Authors: Cazzato Roberto Luigi , Hubelé Fabrice , De Marini Pierre , Ouvrard Eric , Salvadori Julien , Addeo Pietro , Garnon Julien , Kurtz Jean-Emmanuel , Greget Michel , Mertz Luc , Goichot Bernard , Gangi Afshin , Imperiale Alessio
Published: December 2021

Neuroendocrine neoplasms (NENs) are rare and heterogeneous epithelial tumors most commonly arising from the gastroenteropancreatic (GEP) system. GEP-NENs account for approximately 60% of all NENs, and the small intestine and pancreas represent two most common sites of primary tumor development. Approximately 80% of metastatic patients have secondary liver lesions, and in approximately 50% of patients, the liver is the only metastatic site. The therapeutic strategy depends on the degree of hepatic metastatic invasion, ranging from liver surgery or percutaneous ablation to palliative treatments to reduce both tumor volume and secretion. In patients with grade 1 and 2 NENs, locoregional nonsurgical treatments of liver metastases mainly include percutaneous ablation and endovascular treatments, targeting few or multiple hepatic metastases, respectively. In the present work, we provide a narrative review of the current knowledge on liver-directed therapy for metastasis treatment, including both interventional radiology procedures and nuclear medicine options in NEN patients, taking into account the patient clinical context and both the strengths and limitations of each modality.
Health-Related Quality of Life and Return to Work after Surgery for Spinal Meningioma: A Population-Based Cohort Study
Authors: Pettersson-Segerlind Jenny , von Vogelsang Ann-Christin , Fletcher-Sandersjöö Alexander , Tatter Charles , Mathiesen Tiit , Edström Erik , Elmi-Terander Adrian
Published: December 2021

Spinal meningiomas are the most common primary spinal intradural tumor. This study aimed to assess Health-related quality of life (HRQoL) and the frequency of return to work in patients surgically treated for spinal meningiomas, in comparison to the general population. Variables were collected from patient charts, EQ-5D-3L, and study specific questionnaires. Patients who had been operated between 2005–2017 were identified in a previous study and those alive in 2020 (104 of 129) were asked to participate. Eighty-four patients (80.8%) with a mean follow-up of 8.7 years, responded and were included. Data was compared to the Stockholm Public Health Survey 2006, a cross-sectional survey of a representative sample of the general population. Analysis for potential non-response bias showed no significant differences. Women in the meningioma sample scored more problems than men with regards to mobility (p = 0.048). There were no significant differences concerning EQ-5Dindex (p = 0.325) or EQVAS (p = 0.116). The correlation between follow-up time and EQ-5Dindex was low (r = 0.167). When comparing HRQoL to the general population sample, no significant differences were found within the EQ-5D-3L dimensions, EQ-5Dindex or EQVAS. Those who postoperatively scored 3–5 on mMCs scored significantly more problems in the EQ-5D-3L dimension mobility (p = 0.023). Before surgery, 41 (48.8%) of the spinal meningioma patients were working and after surgery all returned to work, the majority within three months. Seventy-eight (96%) of the patients would accept surgery for the same diagnosis if asked today. We conclude that surgery for spinal meningiomas is associated with good long-term HRQoL and a high frequency of return to work.
The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma
Authors: Garganese Giorgia , Inzani Frediano , Fragomeni Simona Maria , Mantovani Giulia , Della Corte Luigi , Piermattei Alessia , Santoro Angela , Angelico Giuseppe , Giacò Luciano , Corrado Giacomo , Fagotti Anna , Zannoni Gian Franco , Scambia Giovanni
Published: December 2021

Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.
A Multidisciplinary Diagnostic Approach Reveals a Higher Prevalence of Indolent Systemic Mastocytosis: 15-Years’ Experience of the GISM Network
Authors: Zanotti Roberta , Bonifacio Massimiliano , Isolan Cecilia , Tanasi Ilaria , Crosera Lara , Olivieri Francesco , Orsolini Giovanni , Schena Donatella , Bonadonna Patrizia
Published: December 2021

Systemic mastocytosis (SM) and other adult clonal mast cell disorders (CMD) are often underestimated, and their epidemiology data are scarce. We aimed at evaluating the impact of the activity of the Interdisciplinary Group for Study of Mastocytosis (GISM) of Verona on the prevalence and incidence of CMD. We examined the data of 502 adult patients diagnosed with CMD and residing in the Veneto Region, consecutively referred to GISM between 2006 and 2020. SM was diagnosed in 431 cases, while 71 patients had cutaneous mastocytosis or other CMD. Indolent SM represented the most frequent SM variant (91.0%), mainly with the characteristics of bone marrow mastocytosis (54.8%). The prevalence of SM in the adult population of the Veneto region and of the Verona province was 10.2 and 17.2/100,000 inhabitants, respectively. The mean incidence of new SM cases in Verona was 1.09/100,000 inhabitants/year. Hymenoptera venom allergy was the main reason (50%) leading to the CMD diagnosis. Osteoporosis, often complicated by fragility fractures, was present in 35% of cases, even in young patients, especially males. Our data show a higher prevalence and incidence of SM than previously reported, confirming that reference centers with multidisciplinary approach are essential for the recognition and early diagnosis of CMD.
Intraoperative HIFU Ablation of the Pancreas Using a Toroidal Transducer in a Porcine Model. The First Step towards a Clinical Treatment of Locally Advanced Pancreatic Cancer
Authors: Cilleros Celia , Dupré Aurélien , Chen Yao , Vincenot Jeremy , Rivoire Michel , Melodelima David
Published: December 2021

Apart from palliative chemotherapy, no other therapy has been proven effective for the treatment of locally advanced pancreatic tumors. In this study, an intraoperative high-intensity focused ultrasound (HIFU) device was tested in vivo to demonstrate the feasibility of treating the pancreatic parenchyma and tissues surrounding the superior mesenteric vessels prior to clinical translation of this technique. Twenty pigs were included and treated using a HIFU device equipped with a toroidal transducer and an integrated ultrasound imaging probe. Treatments were performed with energy escalation (from 30 kJ to 52 kJ). All treatments resulted in visible (macroscopically and in ultrasound images) homogeneous thermal damage, which was confirmed by histology. The dimensions of thermal lesions measured in ultrasound images and those measured macroscopically were correlated (r = 0.82, p < 0.05). No arterial spasms or occlusion were observed at the lowest energy setting. Temporary spasm of the peripancreatic artery was observed when using an energy setting greater than 30 kJ. The possibility of treating the pancreas and tissues around mesenteric vessels without vascular thrombosis holds great promise for the treatment of locally advanced pancreatic cancers. If clinically successful, chemotherapy followed by HIFU treatment could rapidly become a novel treatment option for locally advanced pancreatic cancer.
PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword
Authors: Csizmar Clifford M. , Saliba Antoine N. , Swisher Elizabeth M. , Kaufmann Scott H.
Published: December 2021

Despite recent discoveries and therapeutic advances in aggressive myeloid neoplasms, there remains a pressing need for improved therapies. For instance, in acute myeloid leukemia (AML), while most patients achieve a complete remission with conventional chemotherapy or the combination of a hypomethylating agent and venetoclax, de novo or acquired drug resistance often presents an insurmountable challenge, especially in older patients. Poly(ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2, are involved in detecting DNA damage and repairing it through multiple pathways, including base excision repair, single-strand break repair, and double-strand break repair. In the context of AML, PARP inhibitors (PARPi) could potentially exploit the frequently dysfunctional DNA repair pathways that, similar to deficiencies in homologous recombination in BRCA-mutant disease, set the stage for cell killing. PARPi appear to be especially effective in AML with certain gene rearrangements and molecular characteristics (RUNX1-RUNX1T1 and PML-RARA fusions, FLT3- and IDH1-mutated). In addition, PARPi can enhance the efficacy of other agents, particularly alkylating agents, TOP1 poisons, and hypomethylating agents, that induce lesions ordinarily repaired via PARP1-dependent mechanisms. Conversely, emerging reports suggest that long-term treatment with PARPi for solid tumors is associated with an increased incidence of myelodysplastic syndrome (MDS) and AML. Here, we (i) review the pre-clinical and clinical data on the role of PARPi, specifically olaparib, talazoparib, and veliparib, in aggressive myeloid neoplasms and (ii) discuss the reported risk of MDS/AML with PARPi, especially as the indications for PARPi use expand to include patients with potentially curable cancer.
Gram-Scale Synthesis of CoO/C as Base for PtCo/C High-Performance Catalysts for the Oxygen Reduction Reaction
Authors: Mauer Dmitry , Belenov Sergey , Guterman Vladimir , Nikolsky Anatoly , Kozakov Alexey , Nikulin Alexey , Alexeenko Danil , Safronenko Olga
Published: December 2021

The composition, structure, catalytic activity in the ORR and stability of PtCo/C materials, obtained in two stages and compared with commercial Pt/C analogs, were studied. At the first stage of the synthesis performed by electrodeposition of cobalt on a carbon support, a CoOx/C composite containing 8% and 25 wt% cobalt oxide was successfully obtained. In the second step, PtCoOx/C catalysts of Pt1.56Co and Pt1.12Co composition containing 14 and 30 wt% Pt, respectively, were synthesized based on the previously obtained composites. According to the results of the composition and structure analysis of the obtained PtCoOx/C catalysts by X-ray diffraction (XRD), X-ray fluorescence analysis (XRF), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) methods, the formation of small bimetallic nanoparticles on the carbon support surface has been proved. The resulting catalysts demonstrated up to two times higher specific catalytic activity in the ORR and high stability compared to commercial Pt/C analogs.
Assessment on the Effect of Sulfuric Acid Concentration on Physicochemical Properties of Sulfated-Titania Catalyst and Glycerol Acetylation Performance
Authors: Shera Farisya Mohamad Rasid , Irmawati Ramli , Shafizah Ishak Nor , Taufiq-Yap Yun Hin , Muhamad Ernee Noryana , Lee Siew Ling , Salamun Nurrulhidayah
Published: December 2021

In this research, a solid acid catalyst was synthesized to catalyse glycerol acetylation into acetins. The sulphated-titania catalysts were prepared via the wet impregnation method at different sulfuric acid concentrations (5%, 10%, 15%, and 20%) and denoted as 5SA, 10SA, 15SA, and 20SA, respectively. The synthesized catalysts were characterized using FTIR, XRD, TGA, BET, NH3-TPD, XRF, and SEM-EDX. The synthesized catalysts were tested on glycerol acetylation reaction at conditions: 0.5 g catalyst loading, 100–120 °C temperature, 1:6 glycerol/acetic acid molar ratios, and 2–4 h reaction time. The final product obtained was analysed using GC-FID. An increment in sulfuric acid concentration reduces the surface area, pore volume, and particles size. However, the increment has increased the number of active sites (Lewis acid) and strong acid strength. 15SA catalyst exhibited excellent glycerol conversion (>90%) and the highest selectivity of triacetin (42%). Besides sufficient surface area (1.9 m2 g−1) and good porosity structure, the great performance of the 15SA catalyst was attributed to its high acid site density (342.6 µmol g−1) and the high active site of metal oxide (95%).
Removal of Organic Dyes from Water and Wastewater Using Magnetic Ferrite-Based Titanium Oxide and Zinc Oxide Nanocomposites: A Review
Authors: Mapossa António B. , Mhike Washington , Adalima José L. , Tichapondwa Shepherd
Published: December 2021

Heterogeneous photocatalysis using titanium dioxide (TiO2) and zinc oxide (ZnO) has been widely studied in various applications, including organic pollutant remediation in aqueous systems. The popularity of these materials is based on their high photocatalytic activity, strong photosensitivity, and relatively low cost. However, their commercial application has been limited by their wide bandgaps, inability to absorb visible light, fast electron/hole recombination, and limited recyclability since the nanomaterial is difficult to recover. Researchers have developed several strategies to overcome these limitations. Chief amongst these is the coupling of different semi-conductor materials to produce heterojunction nanocomposite materials, which are both visible-light-active and easily recoverable. This review focuses on the advances made in the development of magnetic ferrite-based titanium oxide and zinc oxide nanocomposites. The physical and magnetic properties of the most widely used ferrite compounds are discussed. The spinel structured material had superior catalytic and magnetic performance when coupled to TiO2 and ZnO. An assessment of the range of synthesis methods is also presented. A comprehensive review of the photocatalytic degradation of various priority organic pollutants using the ferrite-based nanocomposites revealed that degradation efficiency and magnetic recovery potential are dependent on factors such as the chemical composition of the heterojunction material, synthesis method, irradiation source, and structure of pollutant. It should be noted that very few studies have gone beyond the degradation efficiency studies. Very little information is available on the extent of mineralization and the subsequent formation of intermediate compounds when these composite catalysts are used. Additionally, potential degradation mechanisms have not been adequately reported.
Microporous Volumes from Nitrogen Adsorption at 77 K: When to Use a Different Standard Isotherm?
Authors: Pires João , Fernandes Rafaela , Pinto Moisés , Batista Mary
Published: December 2021

This work reviews the application of various standard isotherms to evaluate the micropore volume in a range of microporous materials. The selected materials have quite different surface chemistry, and are relevant due to their properties for adsorption and catalysis: zeolites, activated carbons, clay-based materials and MOFs. Some cases were analysed before and after being used as supports in the heterogenization of homogeneous catalysts. The discussion is centred, but not limited, to the three standard isotherms that are mostly employed in the literature (t-curve, non-porous carbon and non-porous hydroxylated silica) for the assessment of the micropore volume. For a given material the values of the micropore volumes from the different standard isotherms were compared, particularly against the values from the largely used t-curve. The cases where major discrepancies were found could normally be ascribed to samples that have a broad micropore size distribution.
Vinylogous and Arylogous Stereoselective Base-Promoted Phase-Transfer Catalysis
Authors: D’Amato Assunta , Della Sala Giorgio
Published: December 2021

Vinylogous enolate and enolate-type carbanions, generated by deprotonation of α,β-unsaturated compounds and characterized by delocalization of the negative charge over two or more carbon atoms, are extensively used in organic synthesis, enabling functionalization and C–C bond formation at remote positions. Similarly, reactions with electrophiles at benzylic and heterobenzylic position are performed through generation of arylogous and heteroarylogous enolate-type nucleophiles. Although widely exploited in metal-catalysis and organocatalysis, it is only in recent years that the vinylogy and arylogy principles have been translated fruitfully in phase-transfer catalyzed processes. This review provides an overview of the methods developed to date, involving vinylogous and (hetero)arylogous carbon nucleophiles under phase-transfer catalytic conditions, highlighting main mechanistic aspects.
Pentamethylcyclopentadienyl Molybdenum(V) Complexes Derived from Iodoanilines: Synthesis, Structure, and ROP of ε-Caprolactone
Authors: Xing Tian , Elsegood Mark R. J. , Dale Sophie H. , Redshaw Carl
Published: December 2021

The reaction of [Mo(η-C5Me5)Cl4] with the ortho-, meta-, or para-iodo-functionalized anilines 2-IC6H4NH2, 3-IC6H4NH2, 4-IC6H4NH2 yields imido or amine products of the type [Mo(η-C5Me5)Cl2(IC6H4N)] (2-I, 1, 3-I, 3, 4-I, 5) or [Mo(η-C5Me5)Cl4(IC6H4NH2)] (3-I, 2, 4-I, 4), respectively, depending on the reaction stoichiometry/conditions; we were unable to isolate an amine complex of the 2-I derivative. The reaction of [Mo(η-C5Me5)Cl4] with one equivalent of 2-I,4-FC6H3NH2 in the presence of Et3N afforded [Mo(η-C5Me5)Cl2(2-I,4-FC6H3N)]·MeCN (6·MeCN), which, upon exposure to air, afforded the Mo(VI) imido complex [Mo(η-C5Me5)Cl3(2-I,4-FC6H3N)] (7). For comparative studies, the structure of the aniline (C6H5NH2)-derived complex [Mo(η-C5Me5)Cl2(2-C6H3N)] (8) has also been prepared. The molecular structures of 1–8 have been determined and reveal packing in the form of zig-zag chains or ladders. The complexes catalyze, in the presence of benzyl alcohol under N2, the ring-opening polymerization (ROP) of ε-caprolactone affording relatively low molecular weight products. The MALDI-ToF spectra indicate that a number of polymer series bearing a variety of end groups are formed. Conducting the ROPs as melts or under air results in the isolation of higher molecular weight products, again bearing a variety of end groups. Kinetic studies reveal the aniline-derived imido complex 8 performs best, whilst a meta-iodo substituent and a Mo(V) centre are also found to be beneficial. The structures of the side products 2-IC6H4NH3Cl and 3-IC6H4NH3Cl are also reported.
Photocatalytic Alkylation of α-(Trifluoromethyl)Styrenes with Potassium Xanthogenates
Authors: Supranovich Vyacheslav I. , Dilman Alexander D.
Published: December 2021

A protocol for the coupling of potassium xanthogenates with α-(trifluoromethyl)styrenes in the presence of triethyl phosphite is reported. The reaction is carried out under blue light irradiation in the presence of organic photocatalyst 3DPAFIPN. The reaction proceeds via formation of alkyl radicals from readily available xanthogenate salts via oxidative desulfurization and cleavage of the carbon–oxygen bond assisted by triethyl phosphite.