bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Building Construction Safety Performance in Different Regions in China
Authors: Xu Jiaying , Meng Qingfeng , Li Xiaoliang , Bao Yanrui , Chong Heap-Yih
Published: July 2023

This article employs a three-stage slack-based data envelopment analysis (SBM-DEA) model to evaluate the construction safety performance (CSP) of 30 provinces and cities in China, focusing on enhancing the sustainable development of construction safety in the industry, in line with the concept of sustainable development. The research findings indicate that the supervision environment of each province and city exerts a more substantial influence on the sustainable development of construction safety compared with the level of socio-economic development. Significant changes have been observed in the regional distribution of construction safety management levels within the construction industry by eliminating the impact of economic development, the supervision environment, and random errors. The original pattern of “East > West > Central > Northeast” has shifted to “East > Central > Northeast > West.” Moreover, it has been discovered that high-efficiency values of safety performance in certain provinces and cities are partially attributed to external environmental (EE) pressure. In contrast, low-efficiency values cannot be solely attributed to their lack of willingness to implement safety management. Finally, the article proposes strategies, including government policy-led approaches, technology prioritization, and management prioritization, to enhance the sustainable development of construction safety in the construction industry based on the internal safety performance of each province.
Impact Dynamic Response of Spherical Net Shells: Finite Element-Based Computational Analysis Investigating the Influence of Dynamic Constitutive Models
Authors: Shen Yuhang , Lin Li , Tang Pengxiao , Xu Tianli
Published: July 2023

The net shell is a widely utilized large-span space structure known for its aesthetically pleasing design and uniform load distribution, as well as serving as a prominent architectural landmark. In recent years, the impact resistance research of mesh and shell structures has garnered increased attention due to the accumulation of local conflicts. In this study, a parametric model of the spherical mesh shell was developed with Rhino software, and a numerical analysis model for a K8 mesh shell was established through the application of the ABAQUS finite element analysis software. Subsequently, the proposed numerical analysis method for the impact test was applied to validate its accuracy. The research also explored various dynamic constitutive models, such as Cowper-Symonds, Johnson-Cook, modified temperature term Johnson-Cook, and modified strain term and temperature term Johnson-Cook, with the assessment of their impact on the numerical simulation of impact resistance. Based on the impact dynamic response of the spherical net shell of different materials, the selection of an appropriate dynamic constitutive model for the numerical simulation of impact resistance in the spherical net shell was the MJ-C model. The comparative analysis of different materials, including Q235B, Q355B, Q460D, and 6061-T6, indicated that when the impact material failed to penetrate the structure instantly, the improvement of the material strength would enhance the impact resistance of the structure. On the other hand, when the impact material managed to penetrate the structure instantly, the material strength would not significantly help mitigate the damage. Notably, brittle materials, such as aluminum alloy, exhibited a distinct absence of a pronounced yield stage compared with low-carbon steel, which ultimately led to a relatively abrupt deformation.
Influence of Opening Type in Axially Compressed Castellated Columns
Authors: Gomes Arthur F. F. , Mesquita Leonardo C. , Rodrigues Edson F. C. , Arroyo Felipe N. , Aquino Vinícius B. M. , Santos Herisson F. , Panzera Túlio H. , Lahr Francisco A. R. , Chahud Eduardo , Branco Luis A. M. N. , Christoforo André L.
Published: July 2023

Recently, castellated columns have been increasingly used in buildings because of their flexibility, easy compatibility and potential savings due to less steel consumption. However, there is a lack of research related to the subject. In view of that, this work evaluates the influence of the opening type and size on the resistant capacity of the column, considering a nonlinear plastic analysis by the finite element method (792 simulations). For this, columns without openings were modeled to validate the methodology proposed. After validation, a nonlinear buckling analysis of castellated columns was performed. In this study, different cut patterns of the beam web are evaluated, as well as residual stresses, material and geometric imperfections, based on a statistical design. The loads obtained by castellated columns and columns without web are compared. Also, the resistance reduction factors associated with global buckling (χ) for castellated profiles are compared to the values proposed by ABNR NBR 8800 (2008). Furthermore, statistically, there are no differences between the opening types evaluated. Finally, in order to contribute to the design of castellated columns, equations based on regression models were found to predict the load capacity of these elements.
Composite Cements Using Ground Granulated Blast Furnace Slag, Fly Ash, and Geothermal Silica with Alkali Activation
Authors: Salas Montoya Andres , Rodríguez-Barboza Loth I. , Colmenero Fonseca Fabiola , Cárcel-Carrasco Javier , Gómez-Zamorano Lauren Y.
Published: July 2023

In recent decades, alkali activated and blended cements have attracted great interest worldwide due to their advantages of low energy cost, high strength, and good durability. This study evaluated the effects of replacing 50% of Portland cement with a mixture of three waste materials: ground granulated blast furnace slag (GGBFS), fly ash (FA), and geothermal waste (GS), with and without external alkaline activation, and activated with different alkali agents: 4 and 7% Na2O equivalent of sodium hydroxide, sodium silicate (water glass), and sodium sulfate. After 90 days of curing, samples were characterized using compressive strength tests, scanning electron microscopy, X-ray diffraction, and thermogravimetric analyses. The results showed that sodium hydroxide caused an alkali–silica reaction and reduced the strength, while sodium silicate and sodium sulfate improved the strength and hydration products formation. Moreover, the addition of fly ash decreased the compressive strength but increased the workability, while the addition of slag and geothermal waste increased strength and densified the matrix with the formation of additional hydration products. The blended cements without activation also showed better performance than pure cement and a more compact matrix of hydration products. The study demonstrated the feasibility of using waste materials to produce blended cements with low energy costs and high durability.
Life Cycle Cost in Circular Economy of Buildings by Applying Building Information Modeling (BIM): A State of the Art
Authors: AlJaber Abdulaziz , Alasmari Esam , Martinez-Vazquez Pedro , Baniotopoulos Charalampos
Published: July 2023

The building industry is one of the largest consumers of materials resources and significant contributors to global waste. Applying core principles of circular economy (CE) could significantly help the environment by reducing waste and decreasing the life cycle cost of buildings. Several strategies to implement the concept of CE in buildings include design for deconstruction, adaptability, and flexibility. However, implementing these design strategies could face constraints. In this study, we identified 22 barriers related to the adoption of CE in buildings, as reported in the literature. We discussed the role of Building Information Modeling (BIM) in overcoming those barriers. This paper demonstrates how BIM can facilitate the implementation of CE principles while providing critical insights into the life cycle costs of circular buildings. We identified 14 ways to use BIM to foster the implementation of a circular economy approach. To achieve these objectives, we have undertaken a thorough review of recent publications that explore CE design strategies, Life Cycle Costing in the circular construction of buildings, and BIM developments in the building industry. This literature review is based on 88 articles covering BIM’s role in enhancing the management of a building’s end-of-life while reducing the life cycle cost in the circular construction of buildings.
Developing Indicators for Healthy Building in Taiwan Using Fuzzy Delphi Method and Analytic Hierarchy Process
Authors: Shao Wen-Cheng , Chen Jia-Wei , Dong Yu-Wei , Lu Chao-Ling , Chiou Yi-Ting
Published: July 2023

Healthy buildings are the future of industrial development and a global trend. This study is based on the local demand in Taiwan for the certification of healthy building assessments. It consolidates fifteen relevant assessment indicators and the literature on healthy buildings and green buildings from both domestic and international sources. Through expert questionnaires, the study investigates the importance and weight values of assessment items, selecting seven assessment indicators (air, water, light, exercise, comfort, materials, and mental well-being), seventeen assessment items, and 65 assessment sub-items. The weight values of each indicator are statistically analyzed. Based on the expert questionnaires, a rating system and scoring criteria are formulated, ultimately constructing the “Taiwan Healthy Building Assessment Indicators.” The aim is for this framework to serve as a reference for the government in establishing a healthy building certification system as well as to enhance public awareness and emphasis on human health.
Housing Design: Furniture or Fixtures? Accommodating Change through Technological and Typological Innovation
Authors: Daglio Laura , Ginelli Elisabetta , Vignati Giulia
Published: July 2023

The recent global pandemic has sped up architectural research in residential design aimed at rethinking housing layouts, services, and construction methods to accommodate the changing needs of the rapidly evolving contemporary society. New typological and technological design approaches are required to address, on the one hand, the adaptability of the plan as a result of higher flexibility and temporariness in familiar and working patterns, together with a downsizing of the layouts to ensure affordability and quality of life. On the other hand, the issues of sustainability and circular economy require specific attention to interpret the resilience of the building and the reuse/recycle of the fit-out systems. The paper aims at interpreting the notion of integration between fixtures and furnishing in housing design, based on a comprehensive literature review enriched with a case study analysis that shows design concepts and approaches rooted in theories and experiences of 20th-century architecture. Principles, potentials, and barriers to the development of integrated systems are highlighted and the possible implementation of industrialised production components, the potential for modularity, flexibility, and assembly are discussed.
Exploring the Effect of Varying Fiber Dosages as Stirrup Substitutes in Torsion-Loaded Concrete Beams
Authors: Jaber Muna H. , Abd Al-Zahra Bilal I. , Ibrahim Ayoob A. , Hassan Rafea F. , Al-Salim Nabeel H. , Hussein Husam H.
Published: July 2023

Over the past few decades, numerous studies have explored the use of steel fiber (SF) as an alternative to transverse reinforcement rebars in reinforced concrete beams, either partially or completely replacing them. However, there are limited studies that have investigated the effect of fiber dosage and length on reinforced concrete beam performance under torsional loads without the use of transverse reinforcement rebars. In this study, experimental investigations were conducted to examine the performance of reinforced SF concrete beams subjected to torsional load, utilizing SFs as a complete substitution of transverse reinforcement rebars. Ten different concrete mixes with varying dosages of SFs, namely 0%, 0.5%, 1.0%, and 1.5%, were examined while maintaining the same aspect ratio for fiber length and diameter. The results revealed that the addition of SFs in the concrete mix had an impact on its properties, reducing workability but increasing flexural, tensile, and compressive strengths. By incorporating 1.0% of SFs in the concrete mix, the missing torsional strength resulting from the absence of stirrups was adequately compensated. Moreover, the presence of SFs significantly influenced the ductile behavior beyond the point of cracking in the tested beams. Hence, it is recommended that SFs are incorporated with dosages of 1.0% and 1.5% in the concrete mixture, particularly for beams subjected to torsion, as a viable substitute for stirrups.
Can Technology Reinforce Cogency of the Architectural Argument: Trial and Error Approach
Authors: Atanacković Jeličić Jelena , Rapaić Milan R. , Maraš Igor , Tot Erne , Ecet Dejan
Published: July 2023

The main question proposed in this research is whether different types of organizational approaches could help in shortening the response time needed to analyze advanced design solutions in accordance with the changed circumstances. Approaches that we are considering have been adapted from rapidly changing disciplines—such as the IT industry, and software engineering. This paradigm allows for architectural programming to obtain different positions in the timeline of project planning and realization. We proposed a novel methodology of architectural design and project management as an instrument inspired by the Agile Manifesto and some of its instantiations, most notably by the Scrum framework. This research shows that application of the proposed framework significantly shortens the design process and facilitates the involvement of a larger number of authors within the same project team. This study focused on the specific case of architectural competitions. However, the results showed that the same framework could be applied in a broader design context, details of which have been left for future considerations.
Adsorption of Cobalt and Strontium Ions on Plant-Derived Activated Carbons: The Suggested Mechanisms
Authors: Ceban (Ginsari) Irina , Lupascu Tudor , Mikhalovsky Sergey , Nastas Raisa
Published: July 2023

In this study, activated carbons derived from walnut shells (CA-N) and apple wood (CA-M) were used as adsorbents to remove cobalt(II) and strontium(II) ions from aqueous solutions. The novel materials were obtained using nitric acid (CA-Mox) and nitric acid/urea mixture (CA-Mox-u, CA-Nox-u) as oxidizing agents. The physical–chemical characteristics of activated carbons were determined from nitrogen sorption isotherms, SEM-EDX, FTIR, pH metric titrations, the Boehm titration method and elemental analysis. The results of batch experiments indicate that maximum adsorption can be achieved in broad pH ranges: 4–8 for Co(II) and 4–10 for Sr(II). The maximum adsorption capacities of Co(II) and Sr(II) on oxidized activated carbons at pH = 4 are: CA-Mox, 0.085 and 0.076 mmol/g; CA-Mox-u, 0.056 and 0.041 mmol/g; and CA-Nox-u, 0.041 and 0.034 mmol/g, respectively. The mathematical models (pseudo-first-order, pseudo-second-order and intraparticle diffusion kinetic models, and Langmuir, Freundlich, Dubinin–Radushkevich, and Temkin–Pyzhev isotherm models) were used to explain the adsorption kinetics, to study the adsorption mechanism and predict maximum adsorption capacity of the adsorbents. The adsorption mechanisms of toxic metal ions on activated carbons were proposed.
Comprehensive Immune Profiling Unveils a Subset of Leiomyosarcoma with “Hot” Tumor Immune Microenvironment
Authors: Feng Xiaolan , Tonon Laurie , Li Haocheng , Darbo Elodie , Pleasance Erin , Macagno Nicolas , Dufresne Armelle , Brahmi Mehdi , Bollard Julien , Ducimetière Francoise , Karanian Marie , Meurgey Alexandra , Pérot Gaëlle , Valentin Thibaud , Chibon Frédéric , Blay Jean-Yves
Published: July 2023

Purpose: To investigate the immune biomarker in Leiomyosarcoma (LMS), which is rare and recognized as an immune cold cancer showing a poor response rate (<10%) to immune checkpoint inhibitors (ICIs). However, durable response and clinical benefit to ICIs has been observed in a few cases of LMS, including, but not only, LMS with tertiary lymphoid structure (TLS) structures. Patients and methods: We used comprehensive transcriptomic profiling and a deconvolution method extracted from RNA-sequencing gene expression data in two independent LMS cohorts, the International Cancer Genome Consortium (ICGC, N = 146) and The Cancer Genome Atlas (TCGA, N = 75), to explore tumor immune microenvironment (TIME) in LMS. Results: Unsupervised clustering analysis using the previously validated two methods, 90-gene signature and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), identified immune hot (I-H) and immune high (I-Hi) LMS, respectively, in the ICGC cohort. Similarly, immune active groups (T-H, T-Hi) were identified in the TCGA cohort using these two methods. These immune active (“hot”) clusters were significantly associated, but not completely overlapping, with several validated immune signatures such as sarcoma immune class (SIC) classification and TLS score, T cell inflamed signature (TIS) score, immune infiltration score (IIS), and macrophage score (M1/M2), with more patients identified by our clustering as potentially immune hot. Conclusions: Comprehensive immune profiling revealed a subset of LMS with a distinct active (“hot”) TIME, consistently associated with several validated immune signatures in other cancers. This suggests that the methodologies that we used in this study warrant further validation and development, which can potentially help refine our current immune biomarkers to select the right LMS patients for ICIs in clinical trials.
Characterization of Lymph Node Tumor Burden in Node-Positive Prostate Cancer Patients after Robotic-Assisted Radical Prostatectomy with Extended Pelvic Lymph Node Dissection
Authors: Gottlieb Josh , Chang Shu-Ching , Choe Jane , Grunkemeier Gary L. , Hanes Douglas A. , Krasne David , Hoon Dave S. B. , Wilson Timothy G.
Published: July 2023

Background: Prostate cancer (PCa) nodal staging does not account for lymph node (LN) tumor burden. The LN anatomical compartment involved with the tumor or the quantified extent of extranodal extension (ENE) have not yet been studied in relation to biochemical recurrence-free survival (BRFS). Methods: Histopathological slides of 66 pN1 PCa patients who underwent extended pelvic lymph node dissection were reviewed. We recorded metrics to quantify LN tumor burden. We also characterized the LN anatomical compartments involved and quantified the extent of ENE. Results: The median follow-up time was 38 months. The median number of total LNs obtained per patient was 30 (IQR 23–37). In the risk-adjusted cox regression model, the following variables were associated with BRFS: mean size of the largest LN deposit per patient (log2: adjusted hazard ratio (aHR) = 1.91, p < 0.001), the mean total span of all LN deposits per patient (2.07, p < 0.001), and the mean percent surface area of the LN involved with the tumor (1.58, p < 0.001). There was no significant BRFS association for the LN anatomical compartment or the quantified extent of ENE. Conclusion: LN tumor burden is associated with BRFS. The LN anatomical compartments and the quantified extent of ENE did not show significant association with BRFS.
Using Single-Voxel Magnetic Resonance Spectroscopy Data Acquired at 1.5T to Classify Multivoxel Data at 3T: A Proof-of-Concept Study
Authors: Ungan Gülnur , Pons-Escoda Albert , Ulinic Daniel , Arús Carles , Vellido Alfredo , Julià-Sapé Margarida
Published: July 2023

In vivo magnetic resonance spectroscopy (MRS) has two modalities, single-voxel (SV) and multivoxel (MV), in which one or more contiguous grids of SVs are acquired. Purpose: To test whether MV grids can be classified with models trained with SV. Methods: Retrospective study. Training dataset: Multicenter multiformat SV INTERPRET, 1.5T. Testing dataset: MV eTumour, 3T. Two classification tasks were completed: 3-class (meningioma vs. aggressive vs. normal) and 4-class (meningioma vs. low-grade glioma vs. aggressive vs. normal). Five different methods were tested for feature selection. The classification was implemented using linear discriminant analysis (LDA), random forest, and support vector machines. The evaluation was completed with balanced error rate (BER) and area under the curve (AUC) on both sets. The accuracy in class prediction was calculated by developing a solid tumor index (STI) and segmentation accuracy with the Dice score. Results: The best method was sequential forward feature selection combined with LDA, with AUCs = 0.95 (meningioma), 0.89 (aggressive), 0.82 (low-grade glioma), and 0.82 (normal). STI was 66% (4-class task) and 71% (3-class task) because two cases failed completely and two more had suboptimal STI as defined by us. Discussion: The reasons for failure in the classification of the MV test set were related to the presence of artifacts.
Grade Progression and Intrapatient Tumor Heterogeneity as Potential Contributors to Resistance in Gastroenteropancreatic Neuroendocrine Tumors
Authors: Varghese Diana Grace , Del Rivero Jaydira , Bergsland Emily
Published: July 2023

Gastroenteropancreatic neuroendocrine neoplasms (NENs) are a heterogenous group of tumors that are incurable when metastatic, regardless of grade. The aim of this article is to understand tumor heterogeneity and grade progression as possible contributors to drug resistance in gastroentropancreatic neuroendocrine tumors (GEP-NETs). Heterogeneity has been observed in the genetic, pathological, and imaging features of these tumors at baseline. Diagnostic challenges related to tumor sampling and the potential for changes in grade over time further confound our ability to optimize therapy for patients. A better understanding of NEN biology and tumor heterogeneity at baseline and over time could lead to the development of new therapeutic avenues.
The Prognostic Role of Human Papillomavirus and p16 Status in Penile Squamous Cell Carcinoma—A Systematic Review
Authors: Parza Kevin , Mustasam Arfa , Ionescu Filip , Paravathaneni Mahati , Sandstrom Reagan , Safa Houssein , Grass G. Daniel , Johnstone Peter A. , Eschrich Steven A. , Chadha Juskaran , Zacharias Niki , Pettaway Curtis A. , Spiess Philippe E. , Chahoud Jad
Published: July 2023

PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide.
A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show 18F-Fluorothymidine “Flare” on Positron Emission Tomography
Authors: Aravind Preetha , Popat Sanjay , Barwick Tara D. , Soneji Neil , Lythgoe Mark , Sreter Katherina B. , Lozano-Kuehne Jingky P. , Bergqvist Mattias , Patel Neva , Aboagye Eric O. , Kenny Laura M.
Published: July 2023

Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory “flare” in 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent 18F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The 18F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed 18F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an 18F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC.
Predictive Risk Score for Acute Kidney Injury in Hematopoietic Stem Cell Transplant
Authors: Rodrigues Natacha , Fragão-Marques Mariana , Costa Cláudia , Branco Carolina , Marques Filipe , Vasconcelos Pedro , Martins Carlos , Leite-Moreira Adelino , Lopes José António
Published: July 2023

Hematopoietic stem cell transplant (HSCT) is an important treatment option for hematologic malignancies. Acute kidney injury (AKI) is a common complication in HSCTs and is related to worse outcomes. We aimed to create a predictive risk score for AKI in HSCT considering variables available at the time of the transplant. We performed a retrospective cohort study. AKI was defined by the KDIGO classification using creatinine and urinary output criteria. We used survival analysis with competing events. Continuous variables were dichotomized according to the Liu index. A multivariable analysis was performed with a backward stepwise regression. Harrel’s C-Statistic was used to evaluate the performance of the model. Points were attributed considering the nearest integer of two times each covariate’s hazard ratio. The Liu index was used to establish the optimal cut-off. We included 422 patients undergoing autologous (61.1%) or allogeneic (38.9%) HSCTs for multiple myeloma (33.9%), lymphoma (27.3%), and leukemia (38.8%). AKI cumulative incidence was 59.1%. Variables eligible for the final score were: hematopoietic cell transplant comorbidity index ≥2 (HR: 1.47, 95% CI: 1.08–2.006; p = 0.013), chronic kidney disease (HR: 2.10, 95% CI: 1.31–3.36; p = 0.002), lymphoma or leukemia (HR: 1.69, 95% CI: 1.26–2.25; p < 0.001) and platelet-to-lymphocyte ratio > 171.9 (HR: 1.43, 95% CI: 1.10–1.86; p = 0.008). This is the first predictive risk score for AKI in patients undergoing HSCTs and the first study where the platelet-to-lymphocyte ratio is independently associated with AKI.
The 2EF Antibody Targets a Unique N-Terminal Epitope of Trop-2 and Enhances the In Vivo Activity of the Cancer-Selective 2G10 Antibody
Authors: Guerra Emanuela , Trerotola Marco , Relli Valeria , Lattanzio Rossano , Ceci Martina , Boujnah Khouloud , Pantalone Ludovica , Di Pietro Roberta , Iezzi Manuela , Tinari Nicola , Alberti Saverio
Published: July 2023

Trop-2 proteolytic processing in cancer cells exposes epitopes that were specifically targeted by the 2G10 antibody. We sought additional recognition of Trop-2 within difficult-to-reach, densely packed tumor sites. Trop-2 deletion mutants were employed in immunization and screening procedures, and these led to the recognition of a novel epitope in the N-terminal region of Trop-2, by the 2EF antibody. The 2EF mAb was shown to bind Trop-2 at cell–cell junctions in MCF-7 breast cancer cells, and in deeply seated sites in prostate cancer, that were inaccessible to benchmark anti-Trop-2 antibodies. The 2EF antibody was shown to inhibit the growth of HT29 colon tumor cells in vitro, with the highest activity at high cell density. In vivo, 2EF showed anticancer activity against SKOv3 ovarian, Colo205, HT29, HCT116 colon and DU-145 prostate tumors, with the highest impact on densely packed tumor sites, whereby 2EF outcompeted benchmark anti-Trop-2 antibodies. Given the different recognition modes of Trop-2 by 2EF and 2G10, we hypothesized the effective interaction of the two mAb in vivo. The 2EF mAb was indeed demonstrated to enhance the activity of 2G10 against tumor xenotransplants, opening novel avenues for Trop-2-targeted therapy. We humanized 2EF by state-of-the-art CDR grafting/re-modeling, yielding the Hu2EF for therapy of Trop-2-expressing tumors in patients.
Lactate Can Modulate the Antineoplastic Effects of Doxorubicin and Relieve the Drug’s Oxidative Damage on Cardiomyocytes
Authors: Rossi Valentina , Govoni Marzia , Di Stefano Giuseppina
Published: July 2023

Background: Doxorubicin (DOXO) is currently administered as the first-choice therapy for a variety of malignancies. Cancer cells exhibit enhanced glycolysis and lactate production. This metabolite affects gene expression and can play a role in chemoresistance. Aim of this study: We investigated whether the enhanced lactate levels that characterize neoplastic tissues can modify the response of cancer cells to DOXO. Methods: After exposing cancer cells to increased lactate levels, we examined whether this metabolite could interfere with the principal mechanisms responsible for the DOXO antineoplastic effect. Results: Increased lactate levels did not affect DOXO-induced topoisomerase poisoning but offered protection against the oxidative damage caused by the drug. This protection was related to changes in gene expression caused by the combined action of DOXO and lactate. Oxidative damage significantly contributed to the heavy cardiotoxicity following DOXO treatment. In cultured cardiomyocytes, we confirmed that DOXO-induced DNA damage and oxidative stress can be significantly mitigated by exposing the cells to increased lactate levels. Conclusions: In addition to contributing to elucidating the effects of the combined action of DOXO and lactate, our results suggest a possible method to reduce the heavy drug cardiotoxicity, a major side effect leading to therapy discontinuation.
Breaking the ‘Undruggable’ Barrier: Anti-PD-1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer Patients with KRAS Mutations—A Comprehensive Review and Description of Single Site Experience
Authors: Chmielewska Izabela , Krawczyk Paweł , Grenda Anna , Wójcik-Superczyńska Magdalena , Krzyżanowska Natalia , Gil Michał , Milanowski Janusz
Published: July 2023

Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations are among the most commonly found oncogenic alterations in non-small cell lung cancer (NSCLC) patients. Unfortunately, KRAS mutations have been considered “undruggable” for many years, making treatment options very limited. Immunotherapy targeting programmed death-ligand 1 (PD-L1), programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has emerged as a promising therapeutic option for NSCLC patients. However, some studies have suggested a lower response rate to immunotherapy in KRAS-mutated NSCLC patients with the coexistence of mutations in the STK11 (Serine/Threonine Kinase 11) gene. However, recent clinical trials have shown promising results with the combination of immunotherapy and chemotherapy or immunotherapy and KRAS inhibitors (sotorasib, adagrasib) in such patients. In other studies, the high efficacy of immunotherapy has been demonstrated in NSCLC patients with mutations in the KRAS gene that do not coexist with other mutations or coexist with the TP53 gene mutations. In this paper, we review the available literature on the efficacy of immunotherapy in KRAS-mutated NSCLC patients. In addition, we presented single-site experience on the efficacy of immunotherapy in NSCLC patients with KRAS mutations. The effectiveness of chemoimmunotherapy or immunotherapy as well as KRAS inhibitors extends the overall survival of advanced NSCLC patients with the G12C mutation in the KRAS gene to 2–3 years. This type of management has become the new standard in the treatment of NSCLC patients. Further studies are needed to clarify the potential benefits of immunotherapy in KRAS-mutated NSCLC patients and to identify potential biomarkers that may help predict response to therapy.
The Role of Salvage Radical Prostatectomy in Patients with Radiation-Resistant Prostate Cancer
Authors: Drobner Jake , Kaldany Alain , Shah Mihir S. , Ghodoussipour Saum
Published: July 2023

There are multiple treatment strategies for patients with localized prostate adenocarcinoma. In intermediate- and high-risk patients, external beam radiation therapy demonstrates effective long-term cancer control rates comparable to radical prostatectomy. In patients who opt for initial radiotherapy but have a local recurrence of their cancer, there is no unanimity on the optimal salvage approach. The lack of randomized trials comparing surgery to other local salvage therapy or observation makes it difficult to ascertain the ideal management. A narrative review of existing prospective and retrospective data related to salvage radical prostatectomy after radiation therapy was undertaken. Based on retrospective and prospective data, post-radiation salvage radical prostatectomy confers oncologic benefits, with overall survival ranging from 84 to 95% at 5 years and from 52 to 77% at 10 years. Functional morbidity after salvage prostatectomy remains high, with rates of post-surgical incontinence and erectile dysfunction ranging from 21 to 93% and 28 to 100%, respectively. Factors associated with poor outcomes after post-radiation salvage prostatectomy include preoperative PSA, the Gleason score, post-prostatectomy staging, and nodal involvement. Salvage radical prostatectomy represents an effective treatment option for patients with biochemical recurrence after radiotherapy, although careful patient selection is important to optimize oncologic and functional outcomes.
Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option
Authors: Molica Stefano , Tam Constantine , Allsup David , Polliack Aaron
Published: July 2023

Ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine–rituximab (BR) in treatment-naive CLL patients. More recently, data from the phase III ALPINE trial, which directly compared zanu with ibrutinib, demonstrated that zanu’s advantages include an improved safety profile as well as enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and the most recent German CLL algorithm suggest that zanu may replace first-generation BTKis as a preferred therapeutic option for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile. Some drug class-related characteristics such as drug resistance, low complete remission (CR) rates, and indefinite treatment duration still remain with zanu, and the results from recently completed and ongoing fixed-duration clinical trials, combining zanu with an anti-BCL2 agent, are eagerly awaited with the possible promise of a reduced treatment duration and lower financial burden.
Photocatalytic Degradation of Ciprofloxacin with Supramolecular Materials Consisting of Nitrogenous Organic Cations and Metal Salts
Authors: Ren Chenfei , Li Jian , Zhang Xingxing , Niu Yunyin
Published: July 2023

The design and synthesis of composite materials with new structures/properties have important practical significance for the degradation of organic pollutants in aquatic environments. On this basis, five new supramolecular materials {[L1]2·[Cu4I8]}(1), {[L1]2·[Ag4I8]}(2), {[L2]·[ZnBr4]}(3), {[L3]2·[AgI5]}(4), {[L3]·[CdBr3Cl]}(5) were synthesized by introducing an amino group into a series of nitrogen-containing cationic ligands (L1–L3) through the reaction of polybromomethylbenzene with 4-aminopyridine. The degradation effect of catalysts 1–5 on ciprofloxacin (CIP) under visible light was studied using their potential catalytic properties. The results showed that compounds 1 and 4 had better degradation effects compared to other compounds. Moreover, compounds 1 and 4 were proved to be excellent catalysts for the photocatalytic degradation of CIP with cyclic experiments. Through further exploration, it was found that neutral conditions and 20 mg compound dosage were more conducive to the photodegradation of CIP by the compound. Through free radical capture experiments, it was found that ·OH played a major role in the photodegradation of CIP.
Core–Shell Catalysts for Conventional Oxidation of Alcohols: A Brief Review
Authors: Correia Luís M. M. , Kuznetsov Maxim L. , Alegria Elisabete C. B. A.
Published: July 2023

This review highlights recent research on the application of core–shell structured materials as catalysts in the oxidation of alcohols to value-added products, such as benzaldehyde, acetophenone, benzophenone, cinnamaldehyde, and vanillin, among others. While the application of various unconventional energy inputs (such as microwave and ultrasound irradiation) was reported, this paper focuses on conventional heating. The oxidation of homocyclic aromatic, heterocyclic aromatic, aliphatic, and alicyclic alcohols catalyzed by core–shell composite catalysts is addressed. This work also highlights some unique advantages of core–shell nanomaterial catalysis, namely the flexibility of combining individual functions for specific purposes as well as the effect of various parameters on the catalytic performance of these materials.
Utilization of Loaded Cobalt onto MCM-48 Mesoporous Catalyst as a Heterogeneous Reaction in a Fixed Bed Membrane Reactor to Produce Isomerization Product from n-Heptane
Authors: Ali Nisreen S. , Salih Issam K. , Harharah Hamed N. , Majdi Hasan Sh. , Salih Hussein G. , Kalash Khairi R. , Al-Shathr Ali , Al-Sudani Farah T. , Abdulrahman Mahir A. , Alrubaye Jamal M. , Albayati Talib M. , Saady Noori M. , Zendehboudi Sohrab
Published: July 2023

The use of catalytic membranes as microstructured reactors without a separative function has proved effective. High catalytic activity is possible with minimal mass transport resistances if the reactant mixture is pushed to flow through the pores of a membrane that has been impregnated with catalyst. In this study, n-heptane (C7H16) was hydrocracked and hydro-isomerized within a plug-flow zeolitic catalytic membrane-packed bed reactor. The metallic cobalt (Co) precursor at 3 wt.% was loaded onto support mesoporous materials MCM-48 to synthesize heterogeneous catalysis. The prepared MCM-48 was characterized by utilizing characterization techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray analysis (EDAX), Fourier transform infrared (FTIR), nitrogen adsorption–desorption isotherms, and the Brunauer–Emmett–Teller (BET) surface area. The structural and textural characteristics of MCM-48 after encapsulation with Co were also investigated. The analyses were performed before and after metal loading. According to the results, the 3 wt.% Co/MCM-48 of metallic catalyst in a fixed bed membrane reactor (MR) appears to have an excellent catalytic activity of ~83% during converting C7H16 at 400 °C, whereas a maximum selectivity was approximately ~65% at 325 °C. According to our findings, the synthesized catalyst exhibits an acceptable selectivity to isomers with multiple branches, while making low aromatic components. In addition, a good catalytic stability was noticed for this catalyst over the reaction. Use of 3 wt.% Co/MCM-48 catalyst led to the highest isomerization selectivity as well as n-heptane conversion. Therefore, the heterogeneous catalysis MCM-48 is a promising option/ alternative for traditional hydrocracking and hydro-isomerization processes.
Comparison of Photocatalytic Biocidal Activity of TiO2, ZnO and Au/ZnO on Escherichia coli and on Aspergillus niger under Light Intensity Close to Real-Life Conditions
Authors: Al Hallak Mohamad , Verdier Thomas , Bertron Alexandra , Castelló Lux Kevin , El Atti Ons , Fajerwerg Katia , Fau Pierre , Hot Julie , Roques Christine , Bailly Jean-Denis
Published: July 2023

Microbial contamination of the surface of building materials and subsequent release of microbial particles into the air can significantly affect indoor air quality. Avoiding the development or, at least, reducing the quantity of microorganisms growing on building materials is a key point to reduce health risks for building occupiers. In that context, the antimicrobial activity of TiO2, ZnO and Au/ZnO was assessed by measuring log reductions of Escherichia coli and Aspergillus niger populations both in the dark and under a light intensity close to real-life conditions. The bactericidal activities (≥2.3 log reduction) of tested products were stronger than their fungicidal activities (≤1.4 log reduction) after 2 h of contact. Different parameters including concentration of photocatalyst, intensity of light (dark vs. 5 W/m2 UV-A), and duration of contact between photocatalyst and microbial cells and spores were investigated. Results of this study confirmed bactericidal activities of TiO2, ZnO and AuZnO on E. coli and brought new insight on their fungicidal activity on the spores of A. niger. They also confirmed the greatest antimicrobial efficiency of ZnO compared to TiO2 and its increased photocatalytic activity when decorated with Au, leading to the highest log reductions detected after 2 h of contact for both tested microorganisms (4 and 1.4 for E. coli and A. niger, respectively). The antimicrobial activity was enhanced by the duration of contact between microorganisms and nanoparticles of the different tested photocatalytic products.
Highly Stable Photocatalytic Dry and Bi-Reforming of Methane with the Role of a Hole Scavenger for Syngas Production over a Defective Co-Doped g-C3N4 Nanotexture
Authors: Tahir Muhammad , Ali Khan Azmat , Bafaqeer Abdullah , Kumar Naveen , Siraj Mohammad , Fatehmulla Amanullah
Published: July 2023

Photocatalytic reduction of CO2 with CH4 through the dry reforming of methane (DRM) is an attractive approach to recycling greenhouse gases into valuable chemicals and fuels; however, this process is quite challenging. Although there is growing interest in designing efficient photocatalysts, they are less stable, and have lower photoactivity when employed for DRM reactions. Herein, we developed a noble metal-free hierarchical graphitic carbon nitride (HC3N4) loaded with cobalt (Co) for highly efficient and stable photocatalytic dry reforming of methane to produce synthesis gases (CO and H2). The performance of the newly designed Co/HC3N4 composite was tested for different reforming systems such as the dry reforming of methane, bi-reforming of methane (BRM) and reforming of CO2 with methanol–water. The performance of HC3N4 was much higher compared to bulk g-C3N4, whereas Co/HC3N4 was found to be promising for higher charge carrier separation and visible light absorption. The yield of CO and H2 with HC3N4 was 1.85- and 1.81-fold higher than when using g-C3N4 due to higher charge carrier separation. The optimized 2% Co/HC3N4 produces CO and H2 at an evolution rate of 555 and 41.2 µmol g−1 h−1, which was 18.28- and 1.74-fold more than using HC3N4 during photocatalytic dry reforming of methane (DRM), with a CH4/CO2 feed ratio of 1.0. This significantly enhanced photocatalytic CO and H2 evolution during DRM was due to efficient charge carrier separation in the presence of Co. The CH4/CO2 feed ratio was further investigated, and a 2:1 ratio was best for CO production. In contrast, the highest H2 was produced with a 1:1 feed ratio due to the competitive adsorption of the reactants over the catalyst surface. The performance of the composite was further investigated for bi-reforming methane and methanol. Using photocatalytic CO2 reduction with CH4/H2O, the production of CO and H2 was reduced, whereas significantly higher CO and H2 evolved using the BRM process involving methanol. Using methanol with CO2 and H2O, 10.77- and 1.39-fold more H2 and CO efficiency was achieved than when using dry reforming of methane. The composite was also very stable for continuous synthesis gas production during DRM in consecutive cycles. Thus, a co-assisted g-C3N4 nanotexture is promising for promoting photocatalytic activity and can be further explored in other solar energy applications.
A Comparative Study of the Antiviral Properties of Thermally Sprayed Coatings against Human Coronavirus HCoV-229E
Authors: Alebrahim Elnaz , Khatibnezhad Hediyeh , Bajgiran Morvarid Mohammadian , Solomon Magan , Liang Chen , Sagan Selena M. , Lima Rogerio S. , Oberste Berghaus Jörg , Aghasibeig Maniya , Moreau Christian
Published: July 2023

For decades, novel viral strains of respiratory tract infections have caused human pandemics and initiated widespread illnesses. The recent coronavirus disease 2019 (COVID-19) outbreak caused by the SARS-CoV-2 virus has raised an urgent need to develop novel antiviral coatings as one of the potential solutions to mitigate the transmission of viral pathogens. Titanium dioxide is considered an excellent candidate for viral disinfection under light irradiation, with the potential to be activated under visible light for indoor applications. This research assessed the antiviral performance of thermally sprayed TiO2 coatings under UVA and ambient light. We also report the antiviral performance of TiO2 composites with other oxides, such as Cu2O and Al2O3, produced by suspension plasma spray, atmospheric plasma spray, and suspension high-velocity oxygen fuel techniques. To evaluate the antiviral performance of the above coatings in a containment level-2 laboratory, a human common cold coronavirus, HCoV-229E, was initially used as a relevant surrogate for SARS-CoV-2. Coatings were also analyzed using SEM and XRD and were classified based on their surface roughness, porosity, and phase composition. Collectively, the thermally sprayed coatings showed comparable or slightly better antiviral activity compared to copper. The most significant level of activity observed was approximately 20% to 50% higher than that of a pure copper plate.