bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on Dynamic Response Characteristics of Stepped Reinforced Retaining Wall
Authors: Zhu Yalin , Chen Renyi , Wang Yixian , Chen Juxiang
Published: September 2022

In order to further explore the influence of reinforcement materials laying position on the dynamic characteristics of reinforced retaining walls, based on FLAC3D finite difference methods for solving nonlinear problems, established with the same size of the retaining wall in practical engineering, the reinforcement material’s relative position in the retaining wall for the normalized processing, under seismic load, and the panel under the conditions of different reinforcement arrangement were analyzed, and the horizontal displacement of slope, the vertical and horizontal earth pressures behind the wall, and the distribution of potential sliding surface were calculated. The relationship between the maximum horizontal displacement of the panel and the laying position of the reinforcement was fitted by MATLAB. The results show that the horizontal displacement of the panel is about 40% smaller when the upper layer of the reinforcement is arranged than that in the lower layer for step 1, and the horizontal displacement of the reinforcement in step 2 is about 30% lower than that in other conditions when the reinforcement is arranged at the top of the slope. The reinforcement arranged in the lower layer of step 1 and the upper layer of step 2 can minimize the wall top displacement. In step 1, the vertical earth pressure and horizontal earth pressure are 19% and 5% smaller than those in other conditions when the reinforcement is arranged near the middle and lower layer of the step. In step 2, the difference between vertical and horizontal earth pressure is not obvious, and the difference between the two conditions is controlled within 5%. At the same time, soil liquefaction and uplift occur under the action of earthquake. The position of sliding crack surface has no obvious regularity with the position of reinforcement, but the position of reinforcement at the step classification is obviously better than other conditions. The fitting formula can describe the relationship between the panel displacement and the position of the reinforcement well. The conclusions can provide a point of reference for practical engineering.
Embodied and Operational Energy of a Case Study Villa in UAE with Sensitivity Analysis
Authors: Rauf Abdul , Attoye Daniel Efurosibina , Crawford Robert
Published: September 2022

Extensive focus on operational energy research has positively impacted both academia and policymakers, facilitating new strategies that reduce the energy consumed by building occupants. Much less emphasis has, however, been given to embodied energy. Consequently, although studies now show that embodied energy can be responsible for up to 50% of a building’s life cycle energy, little is known about the embodied energy associated with the construction of buildings, materials, and components in the study context. The aim of this study is to investigate the current scenario in the United Arab Emirates (UAE) by calculating the embodied energy of a residential villa, and estimating the initial, recurrent, and demolition and disposal embodied energies over a 50-year building life span. A detailed assessment of the embodied energy associated with the construction of the case study villa was carried out using an input–output hybrid approach, followed by a sensitivity analysis focused on variations related to the energy associated and consumed, as well as the adoption of renewable energy sources. The findings show that the initial embodied energy was 57% of the life cycle embodied energy and 19% of the life cycle energy of the villa while the recurrent embodied energy was 43% of the life cycle embodied energy and 14% of the life cycle energy of the villa. The life cycle embodied energy of the villa, over a 50-year life span was 36% of the life cycle energy. This paper also highlights the impact of adding a solar PV system and lists multiple areas for future studies related to embodied energy and its benefit to stakeholders in the building industry.
Laws and Numerical Analysis of Surface Deformation Caused by Excavation of Large Diameter Slurry Shield in Upper-Soft and Lower-Hard Composite Stratum
Authors: Mei Yuan , Zhou Dongbo , Shi Wenyan , Zhang Yuhang , Zhang Yu
Published: September 2022

Due to the large cross-section design of large-diameter shield tunnels, most of the rocks and soils it crosses are composite strata with upper soft and lower hard. In order to reduce the construction cost of shield working shafts, large-diameter shield launching is usually buried at a shallow depth. Based on the typical large-diameter slurry shield tunnel, the following research results were obtained according to field monitoring and PLAXIS 3D finite element simulation. (1) The electronic level is used to monitor the surface settlement, and the field monitoring data were obtained; the surface settlement duration curve at the axis of the shield tunnel during the construction period can be divided into four stages: pre-deformation, shield passing, shield tail exit and shield moving away, of which the surface settlement accounts for the largest proportion during the shield passing. (2) In order to ensure the accuracy of the numerical simulation results, the linear shrinkage of the shield needs to be considered in the modeling. (3) The maximum surface settlement value at the center of the tunnel increases with the increase of the support pressure; when the support pressure exceeds 300 kPa, the surface uplift and the settlement caused by the formation loss will offset, and the surface settlement will decrease instead. The maximum surface settlement value is inversely proportional to the grouting pressure, but with the increase of the grouting pressure, the maximum uplift of the surface continues to increase. (4) With the numerical simulation of excavation step construction, the surface uplift increases with the increase of grouting pressure and shield radius, and decreases with the increase of shield buried depth.
Quantitative and Qualitative Analysis of Applying Building Information Modeling (BIM) for Infrastructure Design Process
Authors: Shin Min-Ho , Jung Ji-Hyun , Kim Hwan-Yong
Published: September 2022

Building information modeling (BIM) has opened up many possibilities for the construction industry. However, most studies focus mainly on its overall uses and management areas. By investigating real projects that could utilize BIM in the design phases for railway construction, the authors examine the possible advantages and disadvantages in BIM implementation. To do so, the authors have selected three projects that utilized BIM implementation during the design process and three other projects with a non-BIM, traditionally designed working environment. Similar-scale projects were carefully chosen, and their differences in costs, man-hours, and labor forces were analyzed quantitatively. In addition, an in-depth interview was conducted with four BIM-designing firms to provide a more comprehensive perspective on the advantages and issues in BIM implementation. The average results showed that BIM-implemented projects spent USD 65,800 less than their counterparts and could increase productivity by about 2.9%. More importantly, the primary difference between BIM and non-BIM projects are in their man-hours. BIM-adopting projects spent 103.5 days less than non-BIM projects on average, and required three fewer professional labor forces during the entire design process.
Design, Development and Implementation of a Novel Parallel Automated Step Response Testing Tool for Building Automation Systems
Authors: Santos Athila , Liu Na , Jradi Muhyiddine
Published: September 2022

The digital transformation has paved the path for new services and efficient management across the value chain of the whole energy sector. For applications behind the meter, buildings stand out as a major contributor to energy consumption and corresponding emissions. Therefore, Building Automation Control Systems (BACS) have been proposed in order to mitigate building performance issues. Finding optimal and automated methods to handle different control points of BACS is very important. In the initial design and commissioning phases, HVAC systems need to be tested exhaustively to guarantee proper function and expected operation compliance. However, the availability of automated step response test tools applied in the building sector is still scarce, forcing engineers around the globe to manually test different scenarios over the same buildings multiple times. This is a tedious and error-prone approach that lacks precision and good resource allocation. Therefore, we propose AUSTRET: a parallel automated multiple processing software for step response testing in buildings. The tool aims to automate the laborious step response tests of BACS cost-effectively. The input parameters can be provided for several control zones and on different control systems. The multi-processing capability allows the step response execution to run in parallel saving time and resources from the operators. The implementation of AUSTRET is first tested in a living lab environment in a university office building and then demonstrated on full-scale in a commercial building setting. The results show how the parallel processing capability of AUSTRET enhances the productivity and efficiency of step response tests in a building and how the different configuration parameters can affect the overall performance of the tests. The preliminary results indicate how automated tools, such as AUSTRET, can improve the automation and effectiveness of step response tests in the design phase or during retro-commissioning building processes.
Machine Learning-Aided Prediction of Post-Fire Shear Resistance Reduction of Q690 HSS Plate Girders
Authors: Liu Guiwen , Liu Jie , Wang Neng , Xue Xuanyi , Tan Youjia
Published: September 2022

Fire has significant effects on the residual resistance of steel structures. It is necessary to accurately clarify its effects on Q690 HSS plate girders, which have been widely used. In this paper, the ultimate resistance and effective service resistance of Q690 HSS plate girders after a fire are obtained using material tests and finite element (FE) analysis including parametric studies, where the data of 210 models were collected. The effects of four key parameters (hw/tw ratio, a/hw ratio, exposure temperature and cooling method) on post-fire shear resistance reduction of Q690 HSS plate girders are roughly investigated by individual conditional expectation (ICE), showing exposure temperature is the most important factor. The popular algorithms of machine learning (ML), namely artificial neural network (ANN) and support vector regression (SVR) algorithms, are utilized in model training to predict the reduction factors of both ultimate resistance and effective service resistance. Finally, the results indicate that the prediction using ML shows much better performance than that with traditional ordinary least squares (OLS) regression, and SVR with genetic algorithm (GA) provides the highest prediction accuracy. The results of this paper show the superiority of machine learning for solving prediction problems of steel structures, compared with conventional methods such as linear regression.
Review of the Cost-Optimal Methodology Implementation in Member States in Compliance with the Energy Performance of Buildings Directive
Authors: Zangheri Paolo , D’Agostino Delia , Armani Roberto , Bertoldi Paolo
Published: September 2022

The building sector has a central role in achieving the European goals of a zero-emission and fully decarbonized stock by 2050. Among the provisions of the Energy Performance of Buildings Directive (EPBD) recast, the implementation of the cost-optimal methodology marked a novel approach in the establishment of minimum energy performance requirements for new and existing buildings. Member States must develop cost-optimal calculations every 5 years to verify and accordingly update the national requirements in force. This paper analyses the latest national cost-optimal reports, providing an updated assessment of the implementation of the cost-optimal methodology throughout Europe. It quantifies the progress in reaching cost-optimal levels in comparison with the previous assessment. It focuses on the conformity and plausibility of calculations in compliance with the policy framework. Furthermore, it evaluates the gap with national requirements, showing that the gap is higher than 15% only in a few Member States. The results provide a comprehensive review of the European progress towards cost-optimality in both the residential sector (average cost-optimal level 80 kWh/m2y for new, 130 kWh/m2y for existing buildings) and the non-residential sector (140 kWh/m2y for new, 180 kWh/m2y for existing buildings). An overall positive development can be inferred from the analysis of the Member States’ progress in the methodology’s implementation. The review also gives inputs for the cost-optimal methodology update foreseen for 2026 (e.g., cost-optimality for districts and historical buildings). The outcomes assume a crucial relevance for the ambitious energy efficiency targets established by Europe.
Research on Experimental and Numerical Methods for Mechanical Properties of Lightweight Hollow Precast Utility Tunnels
Authors: Feng Yutao , Li Weibin , Lu Nan
Published: September 2022

In this paper, the mechanical properties of hollow precast utility tunnels are studied by experimental and numerical methods. Through full-scale experiments, the failure modes of ordinary and hollow utility tunnels are studied, and the failure stages of the structures are classified based on the bearing capacity and damage to the structures. The nonlinear finite element model is used to simulate the behavior of the structure, and the optimal design of the structure under load type and the hollow ratio are discussed based on the finite element method. The theoretical calculation method of the bearing capacity for hollow structures in each stage is proposed, and its application scope is discussed. The finite element analysis can effectively predict the mechanical properties of the structure, and the failure of the utility tunnel structure is dependent on the shear bearing capacity. Although hollow design advances the structural damage under point load, the hollow structure has significant advantages under uniform loads or reasonable hollow ratios. It is reasonable to calculate the cracking load considering moment distribution at section centroid and the failure load considering the combined action of flexural and shear stress, but the hollow ratio should be less than 16%. Under reasonable hollow ratio or load conditions, the hollow design has little effect on the bearing capacity of the structure and can reduce the weight, which has practical value for architecture and construction.
Seismic Performance Evaluation of a High-Rise Building with Structural Irregularities
Authors: Jia Huijuan , Song Yongsheng , Chen Xi , Liu Shunqing , Zhang Binsheng
Published: September 2022

In this study, the seismic performances of a 14-storey office building in Nanjing, China, due to its plan and vertical irregularities in the structural system, were evaluated using the response spectrum method, elastic time history analysis and elastic–plastic time history analysis. In combination of these three methods, the storey drifts and elastic–plastic states of typical structural members under three levels of earthquakes were determined to verify the robustness of the structural design program. The damage states of typical structural members at some sensitive positions were estimated and evaluated under rare earthquakes. Consequently, all structural members were within the scope of elastic performances under the actions of frequent earthquakes. The maximum displacements and storey drifts satisfied the requirements of the design codes within the scope of elastic or elastic–plastic deformations. The induced damages could reach “moderate damage” states, satisfying the requirements for the expected performances by the codes. The consequences indicated that the design scheme and critical parameters for the building structure satisfied the requirements of seismic performances from the codes.
A System Dynamics Approach for Evaluating the Synergy Degree of Social Organizations Participating in Community and Home-Based Elderly Care Services
Authors: Shao Qiuhu , Ma Junwei , Zhu Shiyao
Published: September 2022

As the number of elderly continues to increase in China, anxiety about related problems has encouraged special care for the elderly. Social organizations participating in community and home-based elderly care services (SO-CHECS) seem to be a promising way to address these problems, but it also raises new challenges, such as uncoordinated cooperation among stakeholders, which would lead to low elderly care service quality and hinder the active participation of social organizations. However, synergetic development can be introduced to enhance the participation of social organizations and to improve social welfare. Thus, this study utilizes system dynamics (SD) to investigate how the overall synergy degree of the SO-CHECS system is affected by the dynamic interactions of main elements/subsystems of this system. It also provides a practical tool through which the effectiveness of various management measures in improving the synergy degree of SO-CHECS could be simulated in advance so that the key factors that restrict the development of SO-CHECS can be analyzed and potential effective policies can be designed. In this way, knowledge of the synergic development of the SO-CHECS system will help managers or policy makers to form optimal cooperative relationships among collaborative stakeholders, improve satisfaction for the elderly, and achieve high-efficient resource utilization for the whole city.
A Novel, Quick, and Reliable Smartphone-Based Method for Serum PSA Quantification: Original Design of a Portable Microfluidic Immunosensor-Based System
Authors: Ortega Francisco Gabriel , Gómez Germán E. , González-Martinez Coral , Valero Teresa , Expósito-Hernández José , Puche Ignacio , Rodriguez-Martinez Alba , Serrano María José , Lorente José Antonio , Fernández-Baldo Martín A.
Published: September 2022

We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at −100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL−1 to 1500 pg mL−1. The sensitivity was demonstrated by a detection limit of 2 pg mL−1 and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels.
Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration
Authors: Schrank Travis P. , Kim Sulgi , Rehmani Hina , Kothari Aditi , Wu Di , Yarbrough Wendell G. , Issaeva Natalia
Published: September 2022

Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC.
Targeting Mutant p53 for Cancer Treatment: Moving Closer to Clinical Use?
Authors: Duffy Michael J. , Tang Minhong , Rajaram Subhasree , O’Grady Shane , Crown John
Published: September 2022

Mutant p53 is one of the most attractive targets for new anti-cancer drugs. Although traditionally regarded as difficult to drug, several new strategies have recently become available for targeting the mutant protein. One of the most promising of these involves the use of low molecular weight compounds that promote refolding and reactivation of mutant p53 to its wild-type form. Several such reactivating drugs are currently undergoing evaluation in clinical trials, including eprenetapopt (APR-246), COTI-2, arsenic trioxide and PC14586. Of these, the most clinically advanced for targeting mutant p53 is eprenetapopt which has completed phase I, II and III clinical trials, the latter in patients with mutant TP53 myelodysplastic syndrome. Although no data on clinical efficacy are currently available for eprenetapopt, preliminary results suggest that the drug is relatively well tolerated. Other strategies for targeting mutant p53 that have progressed to clinical trials involve the use of drugs promoting degradation of the mutant protein and exploiting the mutant protein for the development of anti-cancer vaccines. With all of these ongoing trials, we should soon know if targeting mutant p53 can be used for cancer treatment. If any of these trials show clinical efficacy, it may be a transformative development for the treatment of patients with cancer since mutant p53 is so prevalent in this disease.
Current Approaches to the Management of Patients with Endometrial Cancer
Authors: Kalampokas Emmanouil , Giannis Georgios , Kalampokas Theodoros , Papathanasiou Angeliki-Astero , Mitsopoulou Dimitra , Tsironi Evangelia , Triantafyllidou Olga , Gurumurthy Mahalakshmi , Parkin David E. , Cairns Mary , Vlahos Nikolaos F.
Published: September 2022

The incidence of endometrial cancer (EC) is rising and healthcare professionals need to be informed about the latest data on the constant developments in the field of its management. With particular interest in the classification and management of EC, we surveyed current literature, national and international data, and guidelines, as well as the latest studies to present the most recent data regarding the management of EC. It became evident that despite the consensus on low-risk EC, there are still controversies surrounding the management of high-risk EC, especially regarding the role of sentinel lymph node biopsy (SLNB). Our aim is to present the old and new perspectives in the management of EC, the different available surgical routes, the possible desire for fertility preservation, the role of adjuvant therapies and the focus on the advantages and the limitations of the implementation of SLNB in therapeutic strategies. It became evident throughout our search and based on literature data that minimally invasive surgery (MIS) leads to satisfying outcomes, thus becoming gradually the preferred route of surgery, while SLNB could provide essential information and guidance about the overall management needed in cases of both low-risk and high-risk EC.
Feasibility of Leukemia-Derived Exosome Enrichment and Co-isolated dsDNA Sequencing in Acute Myeloid Leukemia Patients: A Proof of Concept for New Leukemia Biomarkers Detection
Authors: Bernardi Simona , Farina Mirko , Bosio Katia , Di Lucanardo Anna , Leoni Alessandro , Re Federica , Polverelli Nicola , Turra Alessandro , Morello Enrico , Accorsi Buttini Eugenia , Zollner Tatiana , Bonvicini Cristian , Malagola Michele , Russo Domenico
Published: September 2022

Exosomes are extracellular vesicles playing a pivotal role in the intercellular communication. They shuttle different cargoes, including nucleic acids from their cell of origin. For this reason, they have been studied as carriers of tumor markers in different liquid biopsy approaches, in particular for solid tumors. Few data are available concerning exosomes as markers of myeloid neoplasia. To better understand their real potential and the best approach to investigate leukemic exosomes, we present the results of a pilot feasibility study evaluating the application of next-generation sequencing analysis of dsDNA derived from exosomes isolated in 14 adult patients affected by acute myeloid leukemias. In particular, leukemia-derived exosome fractions have been analyzed. The concentration of dsDNA co-extracted with exosomes and the number and types of mutations detected were considered and compared with ones identified in the Bone Marrow (BM) and Peripheral Blood (PB) cells. Exosomal DNA concentration, both considering the cargo and the DNA surrounding the lipid membrane resulted in a linear correlation with leukemic burden. Moreover, exosomal DNA mutation status presented 86.5% of homology with BM and 75% with PB. The results of this pilot study confirmed the feasibility of a leukemia-derived exosome enrichment approach followed by exosomal dsDNA NGS analysis for AML biomarker detection. These data point to the use of liquid biopsy in myeloid neoplasia for the detection of active leukemic cells resident in the BM via a painless procedure.
Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood
Authors: Wall Isobelle , Boulat Victoire , Shah Aekta , Blenman Kim R. M. , Wu Yin , Alberts Elena , Calado Dinis Pedro , Salgado Roberto , Grigoriadis Anita
Published: September 2022

During the anti-tumour response to breast cancer, the primary tumour, the peripheral blood, and the lymph nodes each play unique roles. Immunological features at each site reveal evidence of continuous immune cross-talk between them before, during and after treatment. As such, immune responses to breast cancer are found to be highly dynamic and truly systemic, integrating three distinct immune sites, complex cell-migration highways, as well as the temporal dimension of disease progression and treatment. In this review, we provide a connective summary of the dynamic immune environment triad of breast cancer. It is critical that future studies seek to establish dynamic immune profiles, constituting multiple sites, that capture the systemic immune response to breast cancer and define patient-selection parameters resulting in more significant overall responses and survival rates for breast cancer patients.
Concomitant Deep Vein Thrombosis in Cancer Patients with Unsuspected Pulmonary Embolism
Authors: Qdaisat Aiham , Wechsler Adriana H. , Cruz Carreras Maria T. , Menendez Jazmin R. , Lipe Demis , Highsmith Emily A. , Kamal Mona , Al-Breiki Aisha , Rojas Hernandez Cristhiam M. , Wu Carol C. , Yeung Sai-Ching J.
Published: September 2022

Incidental venous thromboembolism (VTE) is common in cancer patients and identifying factors associated with these events can improve the management plan. We studied the characteristics of concomitant deep vein thrombosis (C-DVT) in cancer patients presenting with unsuspected pulmonary embolism (PE) and the association of C-DVT with VTE recurrence and survival outcomes. Patients presenting to our emergency department with confirmed unsuspected/incidental PE between 1 January 2006 and 1 January 2016, were identified. Radiologic reports were reviewed to confirm the presence or absence of C-DVT. Logistic regression analyses and cox regression modeling were used to determine the effect of C-DVT on VTE recurrence and survival outcomes. Of 904 eligible patients, 189 (20.9%) had C-DVT. Patients with C-DVT had twice the odds of developing VTE recurrence (odds ratio 2.07, 95% confidence interval 1.21–3.48, p = 0.007). The mortality rates among C-DVT were significantly higher than in patients without. C-DVT was associated with reduced overall survival in patients with unsuspected PE (hazard ratio 1.33, 95% confidence interval 1.09–1.63, p = 0.005). In conclusion, C-DVT in cancer patients who present with unsuspected PE is common and is associated with an increased risk of VTE recurrence and poor short- and long-term survival. Identifying other venous thrombi in cancer patients presenting with unsuspected PE is recommended and can guide the management plan. For patients with isolated incidental subsegmental pulmonary embolism and concomitant deep vein thrombosis, initiating anticoagulants if no contraindications exist is recommended.
Platinum Plus Tegafur–Uracil versus Platinum Alone during Concurrent Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma: A Propensity-Score-Matching Analysis
Authors: Lien Ching-Feng , Wang Chien-Chung , Yang Chuan-Chien , Wang Chih-Chun , Hwang Tzer-Zen , Shih Yu-Chen , Yeh Shyh-An , Hsieh Meng-Che
Published: September 2022

Concurrent chemoradiotherapy (CCRT) with a cisplatin-based regimen is the standard treatment for patients with nasopharyngeal carcinoma (NPC). Our study was a propensity-score-matching analysis and it aimed to investigate the oncologic outcomes of platinum plus tegafur–uracil versus platinum alone during CCRT in patient with nonmetastatic NPC. Patients with pathologic confirmed NPC in 2018–2022 were reviewed. Patients treated with platinum plus tegafur–uracil (CCRT-UP) or platinum alone (CCRT-P) during CCRT were recruited into this study. A propensity-score-matching analysis was conducted to diminish the selection bias. The recurrence-free survival (RFS) and overall survival (OS) were presented with Kaplan–Meier curves. The treatment-related adverse effects (AEs) were recorded according to the National Cancer Institute’s Common Terminology Criteria V3.0. A total of 44 patients with CCRT-UP and 44 patients with CCRT-P were identified after propensity score matching. The median RFS was not reached (NR) in the CCRT-UP group, and it was 12.5 months in the CCRT-P group (p < 0.001). The median OS was NR in the CCRT-UP group, and it was 15.9 months in the CCRT-P group (p < 0.001). The overall response rate and disease-control rate were insignificant between the CCRT-UP and CCRT-P groups. A subgroup analysis showed that the median OS was significantly longer in the CCRT-UP group than in the CCRT-P group, regardless of the clinical stage. A multivariate analysis exhibited that CCRT-UP was independently correlated with survival. The grade 3–4 AEs were insignificant between the CCRT-UP and CCRT-P arms. CCRT-UP had better RFS and OS in nonmetastatic NPC patients with similar toxic profiles. Further larger-scaled prospective randomized control trials are warranted to validate our conclusions.
The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy
Authors: Kozal Karolina , Krześlak Anna
Published: September 2022

Hypoxia is a common feature associated with many types of cancer. The activity of the hypoxia-inducible factors (HIFs), the critical element of response and adaptation to hypoxia, enhances cancer hallmarks such as suppression of the immune response, altered metabolism, angiogenesis, invasion, metastasis, and more. The HIF-1α and HIF-2α isoforms show similar regulation characteristics, although they are active in different types of hypoxia and can show different or even opposite effects. Breast cancers present several unique ways of non-canonical hypoxia-inducible factors activity induction, not limited to the hypoxia itself. This review summarizes different effects of HIFs activation in breast cancer, where areas such as metabolism, evasion of the immune response, cell survival and death, angiogenesis, invasion, metastasis, cancer stem cells, and hormone receptors status have been covered. The differences between HIF-1α and HIF-2α activity and their impacts are given special attention. The paper also discusses perspectives on using hypoxia-inducible factors as targets in anticancer therapy, given current knowledge acquired in molecular studies.
How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: Loschi Michael , Fenaux Pierre , Cluzeau Thomas
Published: September 2022

TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the myeloid malignancies with the poorest prognosis. In this review, we analyze the prognosis of these two diseases, focussing particularly on the extent of the mono or biallelic mutation status of TP53 mutation, which is largely correlated with cytogenetic complexity. We discuss the possible/potential improvement in outcome based on recent results obtained with new drugs (especially eprenetapopt and magrolimab). We also focus on the impact of allogeneic hematopoietic stem cell transplantation (aHSCT) including post aHSCT treatment.
Utilization of Response Surface Methodology in Optimization and Modelling of a Microbial Electrolysis Cell for Wastewater Treatment Using Box–Behnken Design Method
Authors: Madondo Nhlanganiso Ivan , Rathilal Sudesh , Bakare Babatunde Femi
Published: September 2022

A vast quantity of untreated wastewater is discharged into the environment, resulting in contamination of receiving waters. A microbial electrolysis cell (MEC) is a promising bioelectrochemical system (BES) for wastewater treatment and energy production. However, poor design and control of MEC variables may lead to inhibition in the system. This study explored the utilization of Response Surface Methodology (RSM) on the synergistic aspects of MEC and magnetite nanoparticles for wastewater treatment. Influences of temperature (25–35 °C), voltage supply (0.3–1.3 V) and magnetite nanoparticle dosage (0.1–1.0 g) on the biochemical methane potentials (BMPs) were investigated with the aim of optimizing biogas yield, chemical oxygen demand removal and current density. The analysis of variance (ANOVA) technique verified that the quadratic models obtained were substantial, with p-values below 0.05 and high regression coefficients (R2). The optimum biogas yield of 563.02 mL/g VSfed, chemical oxygen demand (COD) removal of 97.52%, and current density of 26.05 mA/m2 were obtained at 32.2 °C, 0.77 V and 0.53 g. The RSM revealed a good comparison between the predicted and actual responses. This study revealed the effective utilization of statistical modeling and optimization to improve the performance of the MEC to achieve a sustainable and eco-friendly situation.
Ozone as a Catalyst of Surplus Activated Sludge Hydrolysis for the Biogas Production Enhancement
Authors: Paździor Katarzyna , Domińska Marlena , Olak-Kucharczyk Magdalena
Published: September 2022

The biogas produced in the methane fermentation is valuable due to its use as a renewable energy source. A promising method of biogas production intensification is sludge flocs disintegration via ozonation. The aim of this study was to check the impact of the ozonation on the efficiency and kinetics of biogas production from surplus activated sludge (SAS). Processes were carried out batchwise at 37 °C. The following analyses were performed: pH, alkalinity, dry matter, dry organic matter, chemical oxygen demand, total organic carbon, total nitrogen, elemental analysis (CHNS), the biochemical potential of methane by NIR spectroscopy, and the amount and composition of biogas. The results showed that the ozonation process had no effect on the elemental composition and chemical structure of SAS. The chemical formula of SAS (C2.97H4.68O1.20N0.3) and a simplified equation describing the methane fermentation process were determined. Ozonation caused the hydrolysis of some organic compounds from sludge flocs and increased the efficiency of biogas production. The methane content in biogas was higher by about 2.5%, while the amount of produced biogas rose by up to 21% for the ozonized sludge. The kinetic constants of first-order reaction were between 0.219 and 0.323 d−1, with an upward trend due to ozonation.
Exploring the Effect of Hierarchical Porosity in BEA Zeolite in Friedel-Crafts Acylation of Furan and Benzofuran
Authors: Nunes Nelson , Carvalho Ana P. , Elvas-Leitão Ruben , Martins Filomena , Fernandes Auguste , Rocha João , Martins Angela
Published: September 2022

Hierarchical BEA zeolite was prepared through desilication or desilication followed by acid treatment. The catalytic performance of BEA zeolite samples was evaluated using Friedel-Crafts acylations with two substrates of different molecular sizes, furan (5.7 Å) and benzofuran (6.9 Å), in the presence of acetic anhydride as acylating agent. The application of the simplified Langmuir-Hinshelwood kinetic model showed that the size of the substrate leads to different catalytic activities, with improved rate constant and turnover frequency (TOF) solely in the presence of benzofuran for both desilicated and further acid treated samples. The mesopores developed during the zeolite treatments have an important role as transportation channels by reducing diffusion limitations. The application of Quantitative Structure–Property Relationships (QSPR) allowed the finding of the most relevant properties of the zeolite and substrate with impact on the catalytic parameters.
Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
Authors: Paunovic Verica , Peric Stojan , Vukovic Irena , Stamenkovic Marina , Milosevic Emina , Stevanovic Danijela , Mandic Milos , Basta Ivana , Berisavac Ivana , Arsenijevic Mirjana , Bozovic Ivo , Nikolic Marko , Stevic Zorica , Trajkovic Vladimir
Published: September 2022

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain–Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy.
GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target
Authors: Hottin Catherine , Perron Muriel , Roger Jérôme E.
Published: September 2022

Glycogen synthase kinase 3 (GSK3) is a key regulator of many cellular signaling processes and performs a wide range of biological functions in the nervous system. Due to its central role in numerous cellular processes involved in cell degeneration, a rising number of studies have highlighted the interest in developing therapeutics targeting GSK3 to treat neurodegenerative diseases. Although recent works strongly suggest that inhibiting GSK3 might also be a promising therapeutic approach for retinal degenerative diseases, its full potential is still under-evaluated. In this review, we summarize the literature on the role of GSK3 on the main cellular functions reported as deregulated during retinal degeneration, such as glucose homeostasis which is critical for photoreceptor survival, or oxidative stress, a major component of retinal degeneration. We also discuss the interest in targeting GSK3 for its beneficial effects on inflammation, for reducing neovascularization that occurs in some retinal dystrophies, or for cell-based therapy by enhancing Müller glia cell proliferation in diseased retina. Together, although GSK3 inhibitors hold promise as therapeutic agents, we highlight the complexity of targeting such a multitasked kinase and the need to increase our knowledge of the impact of reducing GSK3 activity on these multiple cellular pathways and biological processes.
Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling
Authors: Rioux Geneviève , Turgeon Florence , Le-Bel Gaëtan , Grenier Camille , Guérin Sylvain L. , Pouliot Roxane
Published: September 2022

Psoriasis is a complex, immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms that govern the epidermal defects and immunological dysfunction observed in this condition remain largely unknown. In recent years, the emergence of new, more sophisticated models has allowed the evolution of our knowledge of the pathogenesis of psoriasis. The development of psoriatic skin biomaterials that more closely mimic native psoriatic skin provides advanced preclinical models that will prove relevant in predicting clinical outcomes. In this study, we used a tissue-engineered, two-layered (dermis and epidermis) human skin substitute enriched in T cells as a biomaterial to study both the cellular and molecular mechanisms involved in psoriasis’ pathogenesis. Gene profiling on microarrays revealed significant changes in the profile of genes expressed by the psoriatic skin substitutes compared with the healthy ones. Two genes, namely, PTPRM and NELL2, whose products influence the ERK1/2 signaling pathway have been identified as being deregulated in psoriatic substitutes. Deregulation of these genes supports excessive activation of the ERK1/2 pathway in psoriatic skin substitutes. Most importantly, electrophoresis mobility shift assays provided evidence that the DNA-binding properties of two downstream nuclear targets of ERK1/2, both the NF-κB and Sp1 transcription factors, are increased under psoriatic conditions. Moreover, the results obtained with the inhibition of RSK, a downstream effector of ERK1/2, supported the therapeutic potential of inhibiting this signaling pathway for psoriasis treatment. In conclusion, this two-layered human psoriatic skin substitute enriched in T cells may prove particularly useful in deciphering the mechanistic details of psoriatic pathogenesis and provide a relevant biomaterial for the study of potential therapeutic targets.
L-Ornithine L-Aspartate Restores Mitochondrial Function and Modulates Intracellular Calcium Homeostasis in Parkinson’s Disease Models
Authors: Sisalli Maria Josè , Della Notte Salvatore , Secondo Agnese , Ventra Carmelo , Annunziato Lucio , Scorziello Antonella
Published: September 2022

The altered crosstalk between mitochondrial dysfunction, intracellular Ca2+ homeostasis, and oxidative stress has a central role in the dopaminergic neurodegeneration. In the present study, we investigated the hypothesis that pharmacological strategies able to improve mitochondrial functions might prevent neuronal dysfunction in in vitro models of Parkinson’s disease. To this aim, the attention was focused on the amino acid ornithine due to its ability to cross the blood–brain barrier, to selectively reach and penetrate the mitochondria through the ornithine transporter 1, and to control mitochondrial function. To pursue this issue, experiments were performed in human neuroblastoma cells SH-SY5Y treated with rotenone and 6-hydroxydopamine to investigate the pharmacological profile of the compound L-Ornithine-L-Aspartate (LOLA) as a new potential therapeutic strategy to prevent dopaminergic neurons’ death. In these models, confocal microscopy experiments with fluorescent dyes measuring mitochondrial calcium content, mitochondrial membrane potential, and mitochondrial ROS production, demonstrated that LOLA improved mitochondrial functions. Moreover, by increasing NCXs expression and activity, LOLA also reduced cytosolic [Ca2+] thanks to its ability to modulate NO production. Collectively, these results indicate that LOLA, by interfering with those mitochondrial mechanisms related to ROS and RNS production, promotes mitochondrial functional recovery, thus confirming the tight relationship existing between cytosolic ionic homeostasis and cellular metabolism depending on the type of insult applied.
Low-Ammonium Environment Increases the Nutrient Exchange between Diatom–Diazotroph Association Cells and Facilitates Photosynthesis and N2 Fixation—a Mechanistic Modeling Analysis
Authors: Gao Meng , Armin Gabrielle , Inomura Keisuke
Published: September 2022

Diatom–diazotroph associations (DDAs) are one of the most important symbiotic dinitrogen (N2) fixing groups in the oligotrophic ocean. Despite their capability to fix N2, ammonium (NH4+) remains a key nitrogen (N) source for DDAs, and the effect of NH4+ on their metabolism remains elusive. Here, we developed a coarse-grained, cellular model of the DDA with NH4+ uptake and quantified how the level of extracellular NH4+ influences metabolism and nutrient exchange within the symbiosis. The model shows that, under a fixed growth rate, an increased NH4+ concentration may lower the required level of N2 fixation and photosynthesis, and decrease carbon (C) and N exchange. A low-NH4+ environment leads to more C and N in nutrient exchange and more fixed N2 to support a higher growth rate. With higher growth rates, nutrient exchange and metabolism increased. Our study shows a strong effect of NH4+ on metabolic processes within DDAs, and thus highlights the importance of in situ measurement of NH4+ concentrations.