bluuebunny/crossref_metadata_2025 huggingface dataset:
Eco-Efficiency Assessment Utilizing Recycled Glass Aggregate in Concrete
Authors: Dynan Daniel , Shaikh Faiz , Derry Sonya , Biswas Wahidul
Published: March 2023

This paper reviews specific technical and eco-efficiency performance issues in using glass waste as an aggregate in the production of concrete. Eco-efficiency is a relatively modern tool in the pursuit of sustainability. Eco-efficiency is the concept of maximising the benefits from the use of non-renewable resources while minimising the use of non-renewable resources. The paper details a life cycle assessment and eco-efficiency review of a potentially sustainable alternative to traditional concrete, made from ordinary Portland cement. The study follows the ISO framework, which includes goal and scope, a life cycle inventory, life cycle impact assessment, life cycle costing, normalising of data and the creation of an eco-efficiency portfolio. SimaPro life cycle assessment software has been used to further analyse the use of recycled glass aggregate as a replacement for naturally occurring stone aggregate in geopolymer concrete. The study found that the use of geopolymer concrete as a non-cement based alternative concrete was a viable way to reduce emissions with a high global warming potential but faced challenges in other environmental impact areas. There is a need for ongoing research and study on the application of eco-efficiency as a tool in the pursuit of sustainable practices in society.
A Design and Comparative Analysis of a Home Energy Disaggregation System Based on a Multi-Target Learning Framework
Authors: Buddhahai Bundit , Korkua Suratsavadee Koonlaboon , Rakkwamsuk Pattana , Makonin Stephen
Published: March 2023

Insightful information on energy use encourages home residents to conduct home energy conservation. This paper proposes an experimental design for an energy disaggregation system based on the low-computational-cost approaches of multi-target classification and multi-target regression, which are under the multi-target learning framework. The experiments are set up to determine the optimal learning algorithm and model parameters. In addition, the designated system can provide inference of the appliance power state and the estimated power consumption from both approaches. The kernel density estimation technique is utilized to formulate the appliance power state as a finite-state machine for the multi-target classification approach. Multi-target regression can directly provide the estimation of appliance power demand from the aggregate data, and this work unifies the system’s design together with multi-target classification. The predictive performances obtained through the F-score (micro-averaged) and power estimation accuracy index for the power state inference and the estimated power demand, respectively, are shown to outperform a deep-learning-based denoising autoencoder network under the same data settings from both approaches. The results lead to a recommendation to apply the approach in home energy monitoring, which is mainly based on the characteristics of appliance power and the information that the residents wish to perceive.
Tensile Behavior of Titanium-Clad Bimetallic Steel Butt-Welded Joints
Authors: Jiang Jianbo , Ban Huiyong , Hai Letian , Huang Chenyang
Published: March 2023

Because of the promising corrosion resistance and load-bearing capacity, titanium-clad (TC) bimetallic steel has gained increasing attention in ocean/coastal civil and structural engineering. Due to the double-layer nature of TC bimetallic steel, the characteristics of the structural member’s geometry and weld details are considerably different from that of conventional steel members. Even though previous studies have conducted systematical clarifications on parent material of TC bimetallic steels, the mechanical behaviors of weld joints are still vague. This paper firstly describes the manufacture features of TC bimetallic steel welded joints and welded members. Subsequently, the type II and type III butt-welded joints provided by GB/T 13149-2009 are selected to study the corresponding tensile mechanical behavior. Two butt-welded TC bimetallic steel plates were fabricated from hot-rolled bonding TA2 + Q355B TC bimetallic steel and welding wire of ER55-Ni1 and ERTA2ELI. Eight tensile coupons were then extracted from the two welded plates and loaded to failure monotonically. The failure mechanism, stress–strain curves and key mechanical properties are studied and compared with that of parent material. It is found that both types of welded joints possess two fracture points. The first one refers to the fracture of weld joint between the clad layer and titanium cover plate, whilst the second one is the eventual fracture of substrate metal. When the first fracture point is reached, the stress–strain relation exhibits a sharp drop in stress value. Thereafter, a strain-hardening behavior can still be observed prior to the ultimate strength point. The first fracture-induced stress drop of type II joint is less than that of type III joint, whilst the strain-hardening amount of type II joint is more outstanding than that of type III joint. The fracture elongations of type II joint and type III joint are respectively 37% and 57% that of the parent material, whilst the proportions between the ultimate strengths of welded joints and parent material are, respectively, 90% and 93%. In general, the two types of TC bimetallic steel weld joints investigated herein exhibit favorable load-bearing capacity but unfavorable ductility and deformability. Based upon the experimental results, the structural design methodology of welded TC bimetallic steel structure is discussed. The investigations conducted in this paper can provide reference for development of structural design theory of welded TC bimetallic steel structure.
Breast, Prostate, Colorectal, and Lung Cancer Incidence and Risk Factors in Women Who Have Sex with Women and Men Who Have Sex with Men: A Cross-Sectional and Longitudinal Analysis Using UK Biobank
Authors: Underwood Sarah , Lyratzopoulos Georgios , Saunders Catherine L.
Published: March 2023

Background. There is limited evidence about cancer incidence for lesbian, gay and bisexual women and men, although the prevalence of cancer risk factors may be higher. Aim. To describe cancer incidence for four common cancers (breast, lung, colorectal and prostate). Methods. This project used UK Biobank participant data. We explored risk factor prevalence (age, deprivation, ethnicity, smoking, alcohol intake, obesity, parity, and sexual history), and calculated cancer risk, for six groups defined based on sexual history; women who have sex exclusively with men (WSEM), or women (WSEW), women who have sex with men and women (WSWM); men who have sex exclusively with women (MSEW), or men (MSEM), and men who have sex with women and men (MSWM). Results. WSEW, WSWM, MSEM, and MSMW were younger, more likely to smoke, and to live in more deprived neighbourhoods. We found no evidence of an association between sexual history and breast, colorectal, or prostate cancer in age-adjusted models. Lung cancer incidence was higher for WSWM compared with WSEM, HR (95%CI) 1.78 (1.28–2.48), p = 0.0005, and MSWM compared with MSEW, 1.43 (1.03–1.99), p = 0.031; after adjustment for smoking, this difference was no longer significant. Conclusions. Sexual minority groups have a higher risk for lung cancer, due to greater exposure to smoking.
Multimodal Data Integration to Predict Severe Acute Oral Mucositis of Nasopharyngeal Carcinoma Patients Following Radiation Therapy
Authors: Dong Yanjing , Zhang Jiang , Lam Saikt , Zhang Xinyu , Liu Anran , Teng Xinzhi , Han Xinyang , Cao Jin , Li Hongxiang , Lee Francis Karho , Yip Celia Waiyi , Au Kwokhung , Zhang Yuanpeng , Cai Jing
Published: March 2023

(1) Background: Acute oral mucositis is the most common side effect for nasopharyngeal carcinoma patients receiving radiotherapy. Improper or delayed intervention to severe AOM could degrade the quality of life or survival for NPC patients. An effective prediction method for severe AOM is needed for the individualized management of NPC patients in the era of personalized medicine. (2) Methods: A total of 242 biopsy-proven NPC patients were retrospectively recruited in this study. Radiomics features were extracted from contrast-enhanced CT (CECT), contrast-enhanced T1-weighted (cT1WI), and T2-weighted (T2WI) images in the primary tumor and tumor-related area. Dosiomics features were extracted from 2D or 3D dose-volume histograms (DVH). Multiple models were established with single and integrated data. The dataset was randomized into training and test sets at a ratio of 7:3 with 10-fold cross-validation. (3) Results: The best-performing model using Gaussian Naive Bayes (GNB) (mean validation AUC = 0.81 ± 0.10) was established with integrated radiomics and dosiomics data. The GNB radiomics and dosiomics models yielded mean validation AUC of 0.6 ± 0.20 and 0.69 ± 0.14, respectively. (4) Conclusions: Integrating radiomics and dosiomics data from the primary tumor area could generate the best-performing model for severe AOM prediction.
TCF12 Deficiency Impairs the Proliferation of Glioblastoma Tumor Cells and Improves Survival
Authors: Pang Yunong , Zhou Sichang , Zumbo Paul , Betel Doron , Cisse Babacar
Published: March 2023

Isocitrate dehydrogenase (IDH)-wild-type glioblastoma (GBM) is the most common and aggressive primary brain tumor which carries a very poor overall prognosis and is universally fatal. Understanding the transcriptional regulation of the proliferation of GBM tumor cells is critical for developing novel and effective treatments. In this study, we investigate the role of the transcription factor TCF12 in the regulation of GBM proliferation using human and murine GBM cell lines and an in vivo GBM xenograft model. Our study shows that TCF12 deficiency severely impairs proliferation of tumor cells in vitro by disrupting/blocking the G1 to S phase transition. We also discover that TCF12 loss significantly improves animal survival and that TCF12-deficient tumors grow much slower in vivo. Overexpression of TCF12, on the other hand, leads to an increase in the proliferation of tumor cells in vitro and more aggressive tumor progression in vivo. Interestingly, loss of TCF12 leads to upregulation of signature genes of the oligodendrocytic lineage in GBM stem cells, suggesting a role for TCF12 in inhibiting differentiation along the oligodendrocytic lineage. Transcriptomic data also reveals that loss of TCF12 leads to dysregulation of the expression of key genes in the cell cycle. Our work demonstrates critical roles of TCF12 in GBM tumor progression.
Multiple Genes with Potential Tumor Suppressive Activity Are Present on Chromosome 10q Loss in Neuroblastoma and Are Associated with Poor Prognosis
Authors: Ognibene Marzia , De Marco Patrizia , Amoroso Loredana , Cangelosi Davide , Zara Federico , Parodi Stefano , Pezzolo Annalisa
Published: March 2023

Neuroblastoma (NB) is a tumor affecting the peripheral sympathetic nervous system that substantially contributes to childhood cancer mortality. Despite recent advances in understanding the complexity of NB, the mechanisms determining its progression are still largely unknown. Some recurrent segmental chromosome aberrations (SCA) have been associated with poor survival. However, the prognostic role of most SCA has not yet been investigated. We examined a cohort of 260 NB primary tumors at disease onset for the loss of chromosome 10q, by array-comparative genomic hybridization (a-CGH) and Single Nucleotide Polymorphism (SNP) array and we found that 26 showed 10q loss, while the others 234 displayed different SCA. We observed a lower event-free survival for NB patients displaying 10q loss compared to patients with tumors carrying other SCA. Furthermore, analyzing the region of 10q loss, we identified a cluster of 75 deleted genes associated with poorer outcome. Low expression of six of these genes, above all CCSER2, was significantly correlated to worse survival using in silico data from 786 NB patients. These potential tumor suppressor genes can be partly responsible for the poor prognosis of NB patients with 10q loss.
Excitement and Concerns of Young Radiation Oncologists over Automatic Segmentation: A French Perspective
Authors: Bourbonne Vincent , Laville Adrien , Wagneur Nicolas , Ghannam Youssef , Larnaudie Audrey
Published: March 2023

Introduction: Segmentation of organs at risk (OARs) and target volumes need time and precision but are highly repetitive tasks. Radiation oncology has known tremendous technological advances in recent years, the latest being brought by artificial intelligence (AI). Despite the advantages brought by AI for segmentation, some concerns were raised by academics regarding the impact on young radiation oncologists’ training. A survey was thus conducted on young french radiation oncologists (ROs) by the SFjRO (Société Française des jeunes Radiothérapeutes Oncologues). Methodology: The SFjRO organizes regular webinars focusing on anatomical localization, discussing either segmentation or dosimetry. Completion of the survey was mandatory for registration to a dosimetry webinar dedicated to head and neck (H & N) cancers. The survey was generated in accordance with the CHERRIES guidelines. Quantitative data (e.g., time savings and correction needs) were not measured but determined among the propositions. Results: 117 young ROs from 35 different and mostly academic centers participated. Most centers were either already equipped with such solutions or planning to be equipped in the next two years. AI segmentation software was mostly useful for H & N cases. While for the definition of OARs, participants experienced a significant time gain using AI-proposed delineations, with almost 35% of the participants saving between 50–100% of the segmentation time, time gained for target volumes was significantly lower, with only 8.6% experiencing a 50–100% gain. Contours still needed to be thoroughly checked, especially target volumes for some, and edited. The majority of participants suggested that these tools should be integrated into the training so that future radiation oncologists do not neglect the importance of radioanatomy. Fully aware of this risk, up to one-third of them even suggested that AI tools should be reserved for senior physicians only. Conclusions: We believe this survey on automatic segmentation to be the first to focus on the perception of young radiation oncologists. Software developers should focus on enhancing the quality of proposed segmentations, while young radiation oncologists should become more acquainted with these tools.
Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase®, the WHO Pharmacovigilance Database
Authors: Cellier Morgane , Bourneau-Martin Delphine , Abbara Chadi , Crosnier Alexandre , Lagarce Laurence , Garnier Anne-Sophie , Briet Marie
Published: March 2023

Background: Alongside their BCR-ABL specificity, TKIs used in chronic myeloid leukemia also target other tyrosine kinases expressed in the kidney such as PDGFR, c-KIT, SRC, and VEGFR, which may result in specific renal adverse drug reaction (ADR). To evaluate the renal safety profile in real-life conditions, a case/non-case study was performed on VigiBase®, the WHO global safety database. Methods: From 7 November 2001 to 2 June 2021, all cases in which the involvement of imatinib, dasatinib, nilotinib, bosutinib, and ponatinib was suspected in the occurrence of renal ADR were extracted from VigiBase®. Disproportionality analyses were assessed using the reporting odds ratio. Results: A total of 1409 cases were included. Imatinib accounts for half of the reported cases. A signal of disproportionate reporting (SDR) of renal failure and fluid retention was found for the five TKIs. Only dasatinib and nilotinib were related to an SDR for nephrotic syndrome. Nilotinib and ponatinib were related to an SDR for renal artery stenosis, while dasatinib was related to an SDR for thrombotic microangiopathy. No SDR for tubulointerstitial nephritis was observed. Conclusion: This study identified a new safety signal, nephrotic syndrome, for nilotinib and highlights the importance of post-marketing safety surveillance.
Surgical Approach to Liver Metastases in GEP-NET in a Tertiary Reference Center
Authors: Butz Frederike , Dukaczewska Agata , Jann Henning , Dobrindt Eva Maria , Reinhard Lisa , Lurje Georg , Pratschke Johann , Goretzki Peter E. , Schöning Wenzel , Mogl Martina T.
Published: March 2023

Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité—Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome.
Pediatric Patients with Stage IV Rhabdomyosarcoma Significantly Benefit from Long-Term Maintenance Therapy: Results of the CWS-IV 2002 and the CWS DOK IV 2004-Trials
Authors: Tramsen Lars , Bochennek Konrad , Sparber-Sauer Monika , Salzmann-Manrique Emilia , Scheer Monika , Dantonello Tobias , Borkhardt Arndt , Dirksen Uta , Thorwarth Anne , Greiner Jeanette , Ebinger Martin , Weclawek-Tompol Jadwiga , Ladenstein Ruth , Ljungman Gustaf , Hallmen Erika , Lehrnbecher Thomas , Koscielniak Ewa , Klingebiel Thomas
Published: March 2023

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma (STS) in childhood. Whereas more than 90% of patients with localized low-risk RMS can be cured, metastatic RMS have a dismal outcome, with survival rates of less than 30%. The HD CWS-96 trial showed an improved outcome for patients receiving maintenance therapy after completing intensive chemotherapy. Consequently, the international clinical trials CWS-IV 2002 and CWS DOK IV 2004 on metastatic disease of STS of the Cooperative Weichteilsarkom Studiengruppe (CWS) were designed in addition to the CWS-2002P trial for localized RMS disease. All patients received a multimodal intensive treatment regimen. To maintain remission, three options were compared: long-term maintenance therapy (LTMT) versus allogeneic hematopoietic stem cell transplantation (alloHSCT) versus high-dose chemotherapy (HDCT). A total of 176 pediatric patients with a histologically confirmed diagnosis of metastatic RMS or RMS-like tumor were included. A total of 89 patients receiving LTML showed a significantly better outcome, with an event-free survival (EFS) of 41% and an overall survival (OS) of 53%, than alloHSCT (n = 21, EFS 19%, p = 0.02, OS 24%, p = 0.002). The outcome of LTML was slightly improved compared to HDCT (n = 13, EFS 35%, OS 34%). In conclusion, our data suggest that in patients suffering from metastatic RMS, long-term maintenance therapy is a superior strategy in terms of EFS and OS compared to alloHSCT. EFS and OS of HDCT are similar in these strategies; however, the therapeutic burden of LTMT is much lower.
Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma
Authors: Brandt Anna , Thiele Benjamin , Schultheiß Christoph , Daetwyler Eveline , Binder Mascha
Published: March 2023

Tumors shed cell-free DNA (cfDNA) into the plasma. “Liquid biopsies” are a diagnostic test to analyze cfDNA in order to detect minimal residual cancer, profile the genomic tumor landscape, and monitor cancers non-invasively over time. This technique may be useful in patients with head and neck squamous cell carcinoma (HNSCC) due to genetic tumor heterogeneity and limitations in imaging sensitivity. However, there are technical challenges that need to be overcome for the widespread use of liquid biopsy in the clinical management of these patients. In this review, we discuss our current understanding of HNSCC genetics and the role of cfDNA genomic analyses as an emerging precision diagnostic tool.
The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study
Authors: Buda Alessandro , Paniga Cristiana , Taskin Salih , Mueller Michael , Zapardiel Ignacio , Fanfani Francesco , Puppo Andrea , Casarin Jvan , Papadia Andrea , De Ponti Elena , Grassi Tommaso , Mauro Jessica , Turan Hasan , Vatansever Dogan , Gungor Mete , Ortag Firat , Imboden Sara , Garcia-Pineda Virginia , Mohr Stefan , Siegenthaler Franziska , Perotto Stefania , Landoni Fabio , Ghezzi Fabio , Scambia Giovanni , Taskiran Cagatay , Fruscio Robert
Published: March 2023

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.
Comparison of Pathological Outcome and Recurrence Rate between En Bloc Transurethral Resection of Bladder Tumor and Conventional Transurethral Resection: A Meta-Analysis
Authors: Wang Chi-Wei , Lee Ping-Jui , Wu Chih-Wei , Ho Chen-Hsun
Published: March 2023

Current treatment for non-muscle invasive bladder cancer (NMIBC) is the conventional transurethral resection of bladder tumor (CTURBT), but the en bloc transurethral resection of bladder tumor (ERBT) has been gaining more attraction in recent years considering better specimen integrity. Thus, we conducted this meta-analysis to compare the safety and efficacy of ERBT versus CTURBT. Trials were collected from an online database. The primary outcomes included identification of detrusor muscle in specimen, residual tumor, 3, 12, and 24-month recurrence rates and same-site recurrence rate. A total of 31 trials were included. The ERBT group had a higher rate of identification of detrusor muscle in specimens (p = 0.003) and lower residual tumor (p < 0.001). Other than that, lower rates of 3-month (p = 0.005) and 24-month recurrence rate (p < 0.001), same-site recurrence rate (p < 0.001) and complications were also observed. For perioperative outcomes, shorter hospitalization time (HT) (p < 0.001), and catheterization time (CT) (p < 0.001) were also revealed in the ERBT group. No significant difference was found in operative time (OT) (p = 0.93). The use of ERBT showed better pathological outcomes and fewer complications, so it could be considered a more effective treatment option for NMIBC.
Combination of FDG PET/CT Radiomics and Clinical Parameters for Outcome Prediction in Patients with Hodgkin’s Lymphoma
Authors: Ortega Claudia , Eshet Yael , Prica Anca , Anconina Reut , Johnson Sarah , Constantini Danny , Keshavarzi Sareh , Kulanthaivelu Roshini , Metser Ur , Veit-Haibach Patrick
Published: March 2023

Purpose: The aim of the study is to evaluate the prognostic value of a joint evaluation of PET and CT radiomics combined with standard clinical parameters in patients with HL. Methods: Overall, 88 patients (42 female and 46 male) with a median age of 43.3 (range 21–85 years) were included. Textural analysis of the PET/CT images was performed using freely available software (LIFE X). 65 radiomic features (RF) were evaluated. Univariate and multivariate models were used to determine the value of clinical characteristics and FDG PET/CT radiomics in outcome prediction. In addition, a binary logistic regression model was used to determine potential predictors for radiotherapy treatment and odds ratios (OR), with 95% confidence intervals (CI) reported. Features relevant to survival outcomes were assessed using Cox proportional hazards to calculate hazard ratios with 95% CI. Results: albumin (p = 0.034) + ALP (p = 0.028) + CT radiomic feature GLRLM GLNU mean (p = 0.012) (Area under the curve (AUC): 95% CI (86.9; 100.0)—Brier score: 3.9, 95% CI (0.1; 7.8) remained significant independent predictors for PFS outcome. PET-SHAPE Sphericity (p = 0.033); CT grey-level zone length matrix with high gray-level zone emphasis (GLZLM SZHGE mean (p = 0.028)); PARAMS XSpatial Resampling (p = 0.0091) as well as hemoglobin results (p = 0.016) remained as independent factors in the final model for a binary outcome as predictors of the need for radiotherapy (AUC = 0.79). Conclusion: We evaluated the value of baseline clinical parameters as well as combined PET and CT radiomics in HL patients for survival and the prediction of the need for radiotherapy treatment. We found that different combinations of all three factors/features were independently predictive of the here evaluated endpoints.
Machine Learning-Based Radiomic Features on Pre-Ablation MRI as Predictors of Pathologic Response in Patients with Hepatocellular Carcinoma Who Underwent Hepatic Transplant
Authors: Tabari Azadeh , D’Amore Brian , Cox Meredith , Brito Sebastian , Gee Michael S. , Wehrenberg-Klee Eric , Uppot Raul N. , Daye Dania
Published: March 2023

Background: The aim was to investigate the role of pre-ablation tumor radiomics in predicting pathologic treatment response in patients with early-stage hepatocellular carcinoma (HCC) who underwent liver transplant. Methods: Using data collected from 2005–2015, we included adult patients who (1) had a contrast-enhanced MRI within 3 months prior to ablation therapy and (2) underwent liver transplantation. Demographics were obtained for each patient. The treated hepatic tumor volume was manually segmented on the arterial phase T1 MRI images. A vector with 112 radiomic features (shape, first-order, and texture) was extracted from each tumor. Feature selection was employed through minimum redundancy and maximum relevance using a training set. A random forest model was developed based on top radiomic and demographic features. Model performance was evaluated by ROC analysis. SHAP plots were constructed in order to visualize feature importance in model predictions. Results: Ninety-seven patients (117 tumors, 31 (32%) microwave ablation, 66 (68%) radiofrequency ablation) were included. The mean model for end-stage liver disease (MELD) score was 10.5 ± 3. The mean follow-up time was 336.2 ± 179 days. Complete response on pathology review was achieved in 62% of patients at the time of transplant. Incomplete pathologic response was associated with four features: two first-order and two GLRM features using univariate logistic regression analysis (p < 0.05). The random forest model included two radiomic features (diagnostics maximum and first-order maximum) and four clinical features (pre-procedure creatinine, pre-procedure albumin, age, and gender) achieving an AUC of 0.83, a sensitivity of 82%, a specificity of 67%, a PPV of 69%, and an NPV of 80%. Conclusions: Pre-ablation MRI radiomics could act as a valuable imaging biomarker for the prediction of tumor pathologic response in patients with HCC.
Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine
Authors: Spagnol Giulia , Sensi Francesca , De Tommasi Orazio , Marchetti Matteo , Bonaldo Giulio , Xhindoli Livia , Noventa Marco , Agostini Marco , Tozzi Roberto , Saccardi Carlo
Published: March 2023

Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies due to the high prevalence of advanced stages of diagnosis and the high rate of recurrence. Furthermore, the heterogeneity of OC tumors contributes to the rapid development of resistance to conventional chemotherapy. In recent years, in order to overcome these problems, targeted therapies have been introduced in various types of tumors, including gynecological cancer. However, the lack of predictive biomarkers showing different clinical benefits limits the effectiveness of these therapies. This requires the development of preclinical models that can replicate the histological and molecular characteristics of OC subtypes. In this scenario, organoids become an important preclinical model for personalized medicine. In fact, patient-derived organoids (PDO) recapture tumor heterogeneity with the possibility of performing drug screening. However, to best reproduce the patient’s characteristics, it is necessary to develop a specific extracellular matrix (ECM) and introduce a tumor microenvironment (TME), which both represent an actual object of study to improve drug screening, particularly when used in targeted therapy and immunotherapy to guide therapeutic decisions. In this review, we summarize the current state of the art for the screening of PDOs, ECM, TME, and drugs in the setting of OC, as well as discussing the clinical implications and future perspectives for the research of OC organoids.
Diagnostic Accuracy of Magnetic Resonance Imaging in the Pre-Operative Staging of Cervical Cancer Patients Who Underwent Neoadjuvant Treatment: A Clinical–Surgical–Pathologic Comparison
Authors: Ditto Antonino , Leone Roberti Maggiore Umberto , Evangelisti Giulio , Bogani Giorgio , Chiappa Valentina , Martinelli Fabio , Raspagliesi Francesco
Published: March 2023

Magnetic resonance imaging (MRI) has been proven to ensure high diagnostic accuracy in the identification of vaginal, parametrial, and lymph node involvement in patients affected by cervical cancer (CC), thus playing a crucial role in the preoperative staging of the disease. This study aims to compare the accuracy of MRI for the preoperative staging of patients with CC who underwent neoadjuvant treatment (NAT) or direct surgery. Retrospective data analysis of 126 patients with primary CC International Federation of Gynecology and Obstetrics stage IB3-IIB who underwent NAT before radical surgery (NAT group = 94) or received surgical treatment alone (control arm = 32) was prospectively performed. All enrolled patients were clinically assessed with both a pelvic examination and MRI before surgical treatment. Data from the clinical examination were compared with the histopathological findings to assess the accuracy of MRI for staging purposes after NAT or before direct surgery. MRI showed an overall accuracy of 46.1%, proving it to be not superior to pelvic and physical examination. The overall MRI accuracy for the evaluation of parametrial, vaginal, and lymph node status was 65.8%, 79.4%, and 79.4%, respectively. In the NAT group, the accuracy for the detection of parametrial, lymph node, and vaginal involvement was lower than the control group; however, the difference was not significant (p ≥ 0.05). The overall accuracy of MRI for the preoperative staging of CC after NAT is shown to be not unsatisfactory. The limits of MRI staging are especially evident when dealing with pre-treated patients.
Undoped and Fe-Doped Anatase/Brookite TiO2 Mixed Phases, Obtained by a Simple Template-Free Synthesis Method: Physico-Chemical Characterization and Photocatalytic Activity towards Simazine Degradation
Authors: Gervasi Stefano , Blangetti Nicola , Freyria Francesca S. , Guastella Salvatore , Bonelli Barbara
Published: March 2023

For the first time, Fe-doping (0.05, 1.0, and 2.5 wt.% Fe) was performed on a high-surface-area anatase/brookite TiO2 by adopting a simple template-free sol-gel synthesis followed by calcination at a mild temperature. The powders’ textural and surface properties were characterized by following a multi-technique approach. XRD analysis showed that the anatase/brookite ratio slightly varied in the Fe-doped TiO2 (from 76.9/23.1 to 79.3/22.7); Fe doping noticeably affected the cell volume of the brookite phase, which decreased, likely due to Fe3+ ions occupying interstitial positions, and retarded the crystallite growth. N2 sorption at −196 °C showed the occurrence of samples with disordered interparticle mesopores, with an increase in the specific surface area from 236 m2 g−1 (undoped TiO2) to 263 m2 g−1 (2.5 wt.% Fe). Diffuse Reflectance UV-Vis spectroscopy showed a progressive decrease in the bandgap energy from 3.10 eV (undoped TiO2) to 2.85 eV (2.5 wt.% Fe). XPS analysis showed the presence of some surface Fe species only at 2.5 wt.% Fe, and accordingly, the ζ-potential measurements showed small changes in the pH at the isoelectric point. The photocatalytic degradation of simazine (a persistent water contaminant) both under UV and simulated solar light was performed as a probe reaction. Under UV light, Fe-doping improved simazine degradation in the sample at 0.05 wt.% Fe, capable of degrading ca. 77% simazine. Interestingly, the undoped TiO2 was also active both under UV and 1 SUN. This is likely due to the occurrence of anatase/brookite heterojunctions, which help stabilize the photogenerated electrons/holes.
Synthesis of Ce and Sm Co-Doped TiO2 Nanoparticles with Enhanced Photocatalytic Activity for Rhodamine B Dye Degradation
Authors: Slimani Yassine , Almessiere Munirah A. , Mohamed Mohamed J. S. , Hannachi Essia , Caliskan Serkan , Akhtar Sultan , Baykal Abdulhadi , Gondal Mohammed A.
Published: March 2023

One of the major concerns that receive global attention is the presence of organic pollutants (dyes, pharmaceuticals, pesticides, phenolic compounds, heavy metals, and so on), originating from various industries, in wastewater and water resources. Rhodamine B is widely used in the dyeing of paints, plastics, textiles, and other fabrics, as well as biological products. It is highly persistent, toxic, and carcinogenic to organisms and humans when directly released into the water supply. To avoid this hazard, several studies have been conducted in an attempt to remove Rhodamine B from wastewater. Metal oxide semiconducting materials have gained great interest because of their ability to decompose organic pollutants from wastewater. TiO2 is one of the most effective photocatalysts with a broad range of applications. Several attempts have been made to improve its photocatalytic activity. Accordingly, we have prepared in this work a series of cerium (Ce) and samarium (Sm) co-doped TiO2 nanoparticles (x = 0.00, 0.25, 0.50, 1.00, and 2.00%) using a sol–gel auto-combustion approach. The influence of Ce–Sm concentrations on the structural, morphology, electronic, and optical properties, as well as the photocatalytic activity, was investigated. Structure and elemental mapping analyses proved the presence of Ce and Sm in the compositions as well as the development of the TiO2 anatase phase with a tetragonal structure and crystallite size of 15.1–17.8 nm. Morphological observations confirmed the creation of spherical nanoparticles (NPs). The examination of the electronic structure properties using density functional theory (DFT) calculations and of the optical properties using a UV/Vis diffuse spectrophotometer showed a reduction in the bandgap energy upon Ce–Sm co-doping. The photocatalytic activity of the synthesized products was assessed on the degradation of Rhodamine B dye, and it was found that all Ce–Sm co-doped TiO2 nanoparticles have better photocatalytic activities than pristine TiO2 nanoparticles. Among all of the prepared nanoparticles, the sample with x = 0.50% demonstrated the best photocatalytic activity, with a degradation efficiency of 98% within 30 min and a reaction rate constant of about 0.0616 min−1. h+ and •O2− were determined to be the most important active species in the photocatalytic degradation process. Besides the high photocatalytic degradation efficiency, these photocatalysts are highly stable and could be easily recovered and reused, which indicates their potential for practical applications in the future.
Tunable Late-Transition-Metal-Catalyzed Polymerization for Controlled Polymer Synthesis
Authors: Suo Hongyi , Zhang Zisheng , Qu Rui , Gu Yanan , Qin Yusheng
Published: March 2023

As a powerful protocol for the preparation of common polymers, such as polyolefins, polyesters, and polycarbonates, late-transition-metal-catalyzed polymerization can be carried out by controlling the reaction conditions or developing dynamic catalytic systems that use external stimuli to influence the performance of the active sites, resulting in well-defined polymeric materials. In particularly, under the latter conditions, ‘one catalyst’ can provide more than one kind of polymer with a controlled sequence from the monomer mixture, making full use of the prepared catalyst. In this review, tunable modes, including reaction conditions, redox, light or electrochemical properties, Lewis acids, and alkali metal cations, of late-transition-metal-complex (especially iron, cobalt, and nickel)-catalyzed polymerization were collected and thoroughly discussed.
Photocatalytic Performance of Functionalized Biopolymer for Neodymium (III) Sorption and the Recovery from Leachate Solution
Authors: Hamza Mohammed F. , Mira Hamed , Khalafalla Mahmoud S. , Wang Ji , Wei Yuezhou , Yin Xiangbiao , Ning Shunyan , Althumayri Khalid , Fouda Amr
Published: March 2023

Successive grafting of new sorbent bearing amino phosphonic groups based on chitosan nano magnetite particles was performed through successive coupling with formaldehyde. The produced composite was characterized by the high sorption capacity toward rare earth elements (REEs) and consists of different types of functional groups (phosphonic, hydroxyls and amine groups) that are used for enhancing the sorption properties. The chemical modification and the sorption mechanism were investigated through different analytical tools; i.e., FTIR, SEM, SEM-EDX, TGA, BET (surface area) and pHpzc. The sorption was investigated toward Nd(III) as one of the REE(III) members under ultraviolet (UV) and visible light (VL) conditions. The optimum sorption was found at pH0 4 and the sorption capacity was recorded at 0.871 and 0.779 mmol Nd g−1 under UV and VL respectively. Sorption isotherms and uptake kinetics were fitted by Langmuir and Sips and by pseudo-first order rate equation (PFORE) for the functionalized sorbent, respectively. The sorbent showed a relatively high-speed sorption kinetic (20 min). The bounded metal ions were progressively eluted using 0.2 M HCl solution with a desorption rate 10–15 min, while the loss in the total capacity after a series of sorption recycling (sorption/desorption) (five cycles) was limited (around 3%) with 100% of the desorption efficiency, indicating the high stability of the sorbent toward an acidic medium. The sorbent was used for the recovery of REEs from leach liquor residue after pretreatment for the extraction of particular elements. From these results (high loading capacity, high selectivity and high stability against acid treatments), we can see that the sorbent is a promising tool for the selective recovery of rare earth elements in the field of metal valorization.
Palmitate-Induced Cardiac Lipotoxicity Is Relieved by the Redox-Active Motif of SELENOT through Improving Mitochondrial Function and Regulating Metabolic State
Authors: Rocca Carmine , De Bartolo Anna , Guzzi Rita , Crocco Maria Caterina , Rago Vittoria , Romeo Naomi , Perrotta Ida , De Francesco Ernestina Marianna , Muoio Maria Grazia , Granieri Maria Concetta , Pasqua Teresa , Mazza Rosa , Boukhzar Loubna , Lefranc Benjamin , Leprince Jérôme , Gallo Cantafio Maria Eugenia , Soda Teresa , Amodio Nicola , Anouar Youssef , Angelone Tommaso
Published: March 2023

Cardiac lipotoxicity is an important contributor to cardiovascular complications during obesity. Given the fundamental role of the endoplasmic reticulum (ER)-resident Selenoprotein T (SELENOT) for cardiomyocyte differentiation and protection and for the regulation of glucose metabolism, we took advantage of a small peptide (PSELT), derived from the SELENOT redox-active motif, to uncover the mechanisms through which PSELT could protect cardiomyocytes against lipotoxicity. To this aim, we modeled cardiac lipotoxicity by exposing H9c2 cardiomyocytes to palmitate (PA). The results showed that PSELT counteracted PA-induced cell death, lactate dehydrogenase release, and the accumulation of intracellular lipid droplets, while an inert form of the peptide (I-PSELT) lacking selenocysteine was not active against PA-induced cardiomyocyte death. Mechanistically, PSELT counteracted PA-induced cytosolic and mitochondrial oxidative stress and rescued SELENOT expression that was downregulated by PA through FAT/CD36 (cluster of differentiation 36/fatty acid translocase), the main transporter of fatty acids in the heart. Immunofluorescence analysis indicated that PSELT also relieved the PA-dependent increase in CD36 expression, while in SELENOT-deficient cardiomyocytes, PA exacerbated cell death, which was not mitigated by exogenous PSELT. On the other hand, PSELT improved mitochondrial respiration during PA treatment and regulated mitochondrial biogenesis and dynamics, preventing the PA-provoked decrease in PGC1-α and increase in DRP-1 and OPA-1. These findings were corroborated by transmission electron microscopy (TEM), revealing that PSELT improved the cardiomyocyte and mitochondrial ultrastructures and restored the ER network. Spectroscopic characterization indicated that PSELT significantly attenuated infrared spectral-related macromolecular changes (i.e., content of lipids, proteins, nucleic acids, and carbohydrates) and also prevented the decrease in membrane fluidity induced by PA. Our findings further delineate the biological significance of SELENOT in cardiomyocytes and indicate the potential of its mimetic PSELT as a protective agent for counteracting cardiac lipotoxicity.
Current Knowledge about the Impact of Microgravity on Gene Regulation
Authors: Corydon Thomas J. , Schulz Herbert , Richter Peter , Strauch Sebastian M. , Böhmer Maik , Ricciardi Dario A. , Wehland Markus , Krüger Marcus , Erzinger Gilmar S. , Lebert Michael , Infanger Manfred , Wise Petra M. , Grimm Daniela
Published: March 2023

Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.
Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis
Authors: Milosevic Ana , Lavrnja Irena , Savic Danijela , Milosevic Katarina , Skuljec Jelena , Bjelobaba Ivana , Janjic Marija M.
Published: March 2023

Multiple sclerosis (MS) is an autoimmune disease affecting the CNS and occurring far more prevalently in women than in men. In both MS and its animal models, sex hormones play important immunomodulatory roles. We have previously shown that experimental autoimmune encephalomyelitis (EAE) affects the hypothalamic–pituitary–gonadal axis in rats of both sexes and induces an arrest in the estrous cycle in females. To investigate the gonadal status in female rats with EAE, we explored ovarian morphometric parameters, circulating and intraovarian sex steroid levels, and the expression of steroidogenic machinery components in the ovarian tissue. A prolonged state of diestrus was recorded during the peak of EAE, with maintenance of the corpora lutea, elevated intraovarian progesterone levels, and increased gene and protein expression of StAR, similar to the state of pseudopregnancy. The decrease in CYP17A1 protein expression was followed by a decrease in ovarian testosterone and estradiol levels. On the contrary, serum testosterone levels were slightly increased. With unchanged serum estradiol levels, these results point at extra-gonadal sites of sex steroid biosynthesis and catabolism as important regulators of their circulating levels. Our study suggests alterations in the function of the female reproductive system during central autoimmunity and highlights the bidirectional relationships between hormonal status and EAE.
Mesenchymal Stem/Stromal Cells Derived from Cervical Cancer Promote M2 Macrophage Polarization
Authors: Cortés-Morales Víctor Adrián , Chávez-Sánchez Luis , Rocha-Zavaleta Leticia , Espíndola-Garibay Sandra , Monroy-García Alberto , Castro-Manrreza Marta Elena , Fajardo-Orduña Guadalupe Rosario , Apresa-García Teresa , Gutiérrez-de la Barrera Marcos , Mayani Héctor , Montesinos Juan José
Published: March 2023

Macrophages with the M2 phenotype promote tumor development through the immunosuppression of antitumor immunity. We previously demonstrated the presence of mesenchymal stem/stromal cells (MSCs) in cervical cancer (CeCa-MSCs), suggesting an immune protective capacity in tumors, but to date, their effect in modulating macrophage polarization remains unknown. In this study, we compared the capacities of MSCs from normal cervix (NCx) and CeCa to promote M2 macrophage polarization in a coculture system. Our results demonstrated that CeCa-MSCs, in contrast to NCx-MSCs, significantly decreased M1 macrophage cell surface marker expression (HLA-DR, CD80, CD86) and increased M2 macrophage expression (CD14, CD163, CD206, Arg1) in cytokine-induced CD14+ monocytes toward M1- or M2-polarized macrophages. Interestingly, compared with NCx-MSCs, in M2 macrophages generated from CeCa-MSC cocultures, we observed an increase in the percentage of phagocytic cells, in the intracellular production of IL-10 and IDO, the capacity to decrease T cell proliferation and for the generation of CD4+CD25+FoxP3+ Tregs. Importantly, this capacity to promote M2 macrophage polarization was correlated with the intracellular expression of macrophage colony-stimulating factor (M-CSF) and upregulation of IL-10 in CeCa-MSCs. Furthermore, the presence of M2 macrophages was correlated with the increased production of IL-10 and IL-1RA anti-inflammatory molecules. Our in vitro results indicate that CeCa-MSCs, in contrast to NCx-MSCs, display an increased M2-macrophage polarization potential and suggest a role of CeCa-MSCs in antitumor immunity.