bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumed by Boredom: Food Choice Motivation and Weight Changes during the COVID-19 Pandemic
Authors: Van Tilburg Wijnand A. P. , Pekrun Reinhard , Igou Eric R.
Published: September 2022

Boredom is an established cause and correlate of eating behavior. Yet, existing work offers a scattered range of plausible motivations for why this is. We examined among 302 people representative of the adult UK population what motivations they had for selecting food during the COVID-19 pandemic and how this related to boredom. As predicted, bored people choose food less for health reasons and more for convenience. Boredom reduced ethical and ‘natural content’ motivations for selecting food and was not associated with choosing food to regulate one’s mood or to experience unfamiliarity. Boredom was also associated with greater absolute changes in weight over the course of the pandemic. Boredom did not predict weight gains or losses overall. These findings offer insights into the role that boredom plays in eating motivations in particular and health-relevant outcomes in general.
An Evaluation Model of Carbon Emission Reduction Effect of Prefabricated Buildings Based on Cloud Model from the Perspective of Construction Supply Chain
Authors: Sun Shaonan , Chen Yingying , Wang Ailing , Liu Xiaojie
Published: September 2022

Prefabricated buildings are the future direction of the construction industry. The carbon reduction in prefabricated buildings has attracted increasing attention due to its importance to low-carbon and energy savings in the construction industry and achieving China’s “dual carbon” goal. Although research has been conducted on carbon reduction in prefabricated buildings, the use of cloud models for carbon reduction effect evaluation has not been explored. This study therefore aims to develop a cloud model-based evaluation of the carbon emission reduction effect for prefabricated buildings incorporating the characteristics of prefabricated buildings and the building supply chain. The developed model can support assessments of the whole life cycle phases of a prefabricated building. Firstly, carbon flow analysis is carried out from the perspective of the construction supply chain, and the carbon emission reduction effect evaluation index system of prefabricated buildings is established, which contains 5 guideline layers and 26 carbon emission reduction indicators. Secondly, the Continuous Ordered Weighted Averaging operator (C-OWA) is used to calculate the index weight calculation, and the cloud model is applied to conduct a comprehensive evaluation of the carbon emission reduction effect. Finally, this model is applied to evaluate the carbon emission reduction effect in the case of a building. The case study validated the efficiency of the developed model. This study extends the knowledge of carbon emission reduction by addressing specific characteristics of prefabrication and the construction supply chain. This validated model will enhance the willingness to apply prefabricated buildings to reduce carbon emissions and achieve the “dual carbon” goal.
Quantitative Analysis of the Accident Prevention Costs in Korean Construction Projects
Authors: Lee Jaehyun , Jeong Jaewook , Soh Jayho , Jeong Jaemin
Published: September 2022

It is essential to objectively evaluate accident prevention costs (APCs) to respond to high-accident rates in the construction industry. However, currently, no quantitative APC analysis model considers the properties of the Korean construction industry. Therefore, in this study, the APC quantification structure was derived to comprehensively evaluate the properties of Korean construction projects, such as occupational safety and health management funds, safety management expenses, and others. Subsequently, the current status of APC in Korea was analyzed based on case studies on 38 projects for which questionnaires were collected. As a result of the study, the average ratio of the APC to total construction cost of the target project was calculated to be 1.95%. In addition, an average difference exists between groups according to client types and facility types in the target project. This study developed an APC quantification model considering Korea’s safety-related laws and insurance systems. It is expected that the results of this study can be used as objective data for evaluation according to the target project type.
Architecture for a Post-COVID World
Authors: Spennemann Dirk H. R.
Published: September 2022

During the first three months of 2020, COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly developed from a localised disease outbreak into a truly global pandemic [...]
Space Performance Assessment of a Relocatable Health Facility: Mosul Hospital as a Case Study
Authors: Ismael Zhiman Khairi , Khalil Kadhim Fathel
Published: September 2022

Relocatable buildings are commonly spread around as an alternative method of construction. To consider it a successful practice, it should perform its function similarly to a traditional way. Assessing a building after its operation determines the rate of its success and decides the possibility of repeating its type. This study aimed to provide a comprehensive knowledge base related to space evaluation of the building through spatial assessment. This study investigated the functional efficiency and dimensional requirements of a relocatable hospital in Mosul, in the south of Iraq. This study compared the dimensional requirements of eight hospital departments to the standard, followed by functional efficacy analysis based on space syntax theory and compared the results to examples used in standards books. The results showed that departments in the relocatable buildings have good plan integration. We concluded that hospitals constructed with containers could achieve functional efficiency.
Hybrid Model for Forecasting Indoor CO2 Concentration
Authors: Ahn Ki Uhn , Kim Deuk-Woo , Cho Kyungjoo , Cho Dongwoo , Cho Hyun Mi , Chae Chang-U
Published: September 2022

Indoor CO2 concentration is considered a metric of indoor air quality that affects the health of occupants. In this study, a hybrid model was developed for forecasting the varying indoor CO2 concentration levels in a residential apartment unit in the presence of occupants by controlling the ventilation rates of a heat recovery ventilator. In this model, the mass balance equation for a single zone as a white-box model was combined with a Bayesian neural network (BNN) as a black box model. During the learning process of the hybrid model, the BNN estimated an aggregated unknown ventilation rate and transferred the estimation to the mass-balance equation. A parametric study was conducted by changing the prediction horizons of the hybrid model from 5 to 15 min, and the forecasting performance of the hybrid model was compared with the stand-alone mass balance equation. The hybrid model showed better forecasting performance than that of the mass balance equation on the experimental dataset for a living room and bedroom. The average MBE and CVRMSE of the hybrid model for the prediction horizon of 15 min were 0.65% and 5.23%, respectively, whereas those of the mass balance equation were 0.99% and 9.30%, respectively.
Unravelling the Relations between and Predictive Powers of Different Testing Variables in High Performance Concrete Experiments: The Data-Driven Analytical Methods
Authors: Zhuang Zheng-Yun , Kuo Wen-Ten
Published: September 2022

This study proposes and applies a systematic data analysis methodology to analyse experimental data for high-performance concrete (HPC) samples with different admixtures for offshore fan foundation grouting materials uses. In contrast with other relevant research, including experimental studies, the materials physics and chemistry studies, or cementitious material portfolio determination studies, this data-driven analysis provides a deep exploration of the experimental variables associated with the test data. To offer complete and in-depth perspectives, several methods are employed for the data analyses, including correlation analysis, cosine similarity analysis, simple linear regression (SLR) modelling, and heat map and heat-based tabularised visualisations; the outcome is a proposed methodology that is easily implementable. The results from these methods are validated using a pairwise comparison approach (PCA) to avoid unnecessary interference between data variables. There are several potential contributions from this work, including insights for cohered groups of variables, techniques for double check and ‘third check’, an established ‘knowledge base’ consisting of 504 SLR predictive models with their effectiveness (significance) and prediction accuracy (data-model fitness) used in practical applications, an alternative visualisations of the results, three data transforms which can be omitted in a future analysis, and three valuable theory-linking perspectives (e.g., for the relationships between destructive and non-destructive tests with respect to the variable categories). The implication that some variables are interchangeable will make future experiments less labour intensive and time consuming for pre-project HPC material testing.
A Case Study about Energy and Cost Impacts for Different Community Scenarios Using a Community-Scale Building Energy Modeling Tool
Authors: Ye Yunyang , Lei Xuechen , Lerond Jeremy , Zhang Jian , Brock Eli Thomas
Published: September 2022

The United States building sector consumed approximately 75% of electricity in 2019. By implementing renewable energy technologies and control strategies into buildings, future buildings will serve as energy generators as well as consumers. To accommodate this transition, communications among buildings and between buildings and the grid could provide more possibilities to optimize the energy performance of buildings. This paper develops a community-scale building energy model tool and conducts a case study adopting behind-the-meter distributed energy resources, sharing energy in different buildings, and using different electricity tariff structures. Three scenarios are studied: (1) electricity only supplied by the grid, (2) photovoltaic (PV) panels installed on and available to some but not all buildings, and (3) a connected community. To consider the impacts of locations and energy tariffs, this paper selects four cities and three electricity tariffs to evaluate the energy and cost performances of these three scenarios. The results show that the PV panels in Scenario 2 reduce 25% to 33% of the community-level electricity consumption and 20% to 30% of the community-level electricity cost compared with Scenario 1 in all studied locations and energy tariffs. By considering power management in the connected community (Scenario 3), the electricity consumption and cost can be further reduced by 6% to 7% and 5% to 11%, respectively, compared with Scenario 2.
The Study of Architectural Geometry and Shape in the Energy Balance of Glazed Roofs
Authors: Miao Yijia , Liu Ping , Fu Ivan Chin Shing , Lei Qinghua , Lau Stephen Siu Yu , Tao Yiqi
Published: September 2022

Triggered by the global call for low-carbon design, the idea of “productivity for a building envelope” has permeated the role of building to produce alternative (renewable) energy alongside weather and solar protection, and the authors hypothesized that the geometrical shape and configuration of a roof is a significant contributor to low-carbon design. Bibliometric networks such as VOS Viewer revealed a gap among most research works which have yet to discover “roof geometry” as a design determinant for photovoltaic electricity production. In this study, the authors tested their hypothesis by studying and comparing the balancing of solar energy harvesting and energy consumption and saving due to the uncontrolled admittance of daylight, glare, and solar heat gain of different geometric shapes of roofs in the subtropical climate. Twelve recent signature public buildings in Shenzhen city are studied for the tendency of architectural geometry of roof shapes. These roof shapes are then simplified and classified into three distinct geometries—square, pyramidal, and curvilinear—for comparative study of the best-performing low-carbon architectural geometry. The results of the simulations using the “Daysim” and “Energy-Plus” models show the desirability of an optimized design. The preliminary findings shed light on the preferred use of specific roof shapes for enhanced PV output. The curvilinear geometry has been shown to be the most effective of all. This study targeted the roof potentials by multiple criteria and a parametric evaluative protocol for building design known as the energy balance paradigm. This research paves the way in (1) changing the impression of the roof as a mere weather protector to that of a “productive roof” in response to the global call for carbon neutrality, (2) raising the awareness of architectural geometry (i.e., the building envelope), focusing on the roof form and its shape in response to low-carbon design requirements, and (3) identifying multiple criteria for the low-carbon design of architectural roof geometry.
Design Creativity in Architecture and Engineering
Authors: Wodehouse Andrew , Casakin Hernan
Published: September 2022

Creativity is a fundamental topic of study in design, encompassing the formation of new ideas and insights [...]
Effects of Size and Flexural Reinforcement Ratio on Ambient-Cured Geopolymer Slag Concrete Beams under Four-Point Bending
Authors: Mamdouh Hala , Ali Ashraf , Osman Mostafa , Deifalla Ahmed , Ayash Nehal
Published: September 2022

With the rise in cement production required by conventional concrete, CO2 emissions increase, causing pollution to the atmosphere. Geopolymer concrete (GPC) is investigated in the literature as an eco-efficient alternative to conventional concrete (CC). However, most geopolymer studies focus on studying the mechanical properties of GPC, with only limited investigations on the structural performances of structural elements using GPC. The structural behaviors of GPC elements are yet to be completely understood, and there are no current studies on investigating the structural behaviors of geopolymer slag concrete. Thus, this paper investigates the flexural performances of reinforced geopolymer slag concrete beams, focusing on the effects of different beam depths and reinforcement ratios. Five full-scale ambient-cured reinforced geopolymer slag concrete beams were tested under four-point flexure, in addition to one control conventional concrete (CC) beam. The structural performances are evaluated, including the cracking moment, flexural capacity, load–deflection relationship, and crack distribution. The results indicate that the flexural behaviors of GPC beams are comparable to that of the CC beams. Compared to the CC beams, the GPC beams have 7.4% higher flexural moment capacity, 60% lower stiffness, 28% lower ductility, and 18.3% higher toughness. Finally, the Egyptian code of practice ECP 203 and ACI 318 are found to be applicable to safely design under-reinforced GPC flexural beam elements.
Liquid Biopsy-Guided Interventional Oncology: A Proof of Concept with a Special Focus on Radiotherapy and Radiology
Authors: Malara Natalia , Kovacs György , Bussu Francesco , Ferrazzo Teresa , Garo Virginia , Raso Cinzia , Cornacchione Patrizia , Iezzi Roberto , Tagliaferri Luca
Published: September 2022

Although the role of liquid biopsy (LB) to measure minimal residual disease (MRD) in the treatment of epithelial cancer is well known, the biology of the change in the availability of circulating biomarkers arising throughout treatments such as radiotherapy and interventional radio-oncology is less explained. Deep knowledge of how therapeutic effects can influence the biology of the release mechanism at the base of the biomarkers available in the bloodstream is needed for selecting the appropriate treatment-induced tumor circulating biomarker. Combining existing progress in the LB and interventional oncology (IO) fields, a proof of concept is provided, discussing the advantages of the traditional risk assessment of relapsing lesions, limitations, and the timing of detection of the circulating biomarker. The current review aims to help both interventional radiologists and interventional radiation oncologists evaluate the possibility of drawing a tailor-made board of blood-based surveillance markers to reveal subclinical diseases and avoid overtreatment.
Symptom Management and Quality of Life of Breast Cancer Patients Using Acupuncture-Related Therapies and Herbal Medicine: A Scoping Review
Authors: Han Gajin , Lee Ye-Seul , Jang Hee Jae , Kim Song-Yi , Lee Yoon Jae , Ha In-Hyuk
Published: September 2022

The side effects associated with breast cancer treatments often reduce the patients’ quality of life. The effectiveness of acupuncture-related therapies and herbal medicine in managing the side effect is not fully understood. The study included clinical studies published in the 10 years since 2011 and analyzed the effectiveness of the therapies for managing side effects of anticancer treatment. The databases of MEDLINE via PubMed, CENTRAL, EMBASE, OASIS, and NSDL were searched. Thirty studies, including 13 (43.3%) randomized controlled trials (RCTs), 12 (40.0%) before-and-after studies, three (10.0%) case series, one (3.3%) case report, and one (3.3%) non-RCT, were included in this review. The main symptoms identified were aromatase inhibitors-induced arthralgia (AIA), lymphedema, and chemotherapy-induced peripheral neuropathy (CIPN). The types of acupuncture-related therapies applied included manual acupuncture, electro-acupuncture, moxibustion, and electro-moxibustion. In ten studies, eight herbal medications were administered. The Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-General (FACT-G) and -Breast (FACT-B) were frequently used to evaluate pain and QoL, respectively. Most studies suggested beneficial effects of acupuncture and herbal medicine on managing pain, daily function, and quality of life in patients going through AIA, CIPN, and/or lymphedema, with mild side effects. The scoping review implies the potential of CAM therapies as promising interventions for managing symptoms which otherwise lack alternative management options, and for improving the quality of life of breast cancer patients.
BRAFV600E Expression in Thyrocytes Causes Recruitment of Immunosuppressive STABILIN-1 Macrophages
Authors: Spourquet Catherine , Delcorte Ophélie , Lemoine Pascale , Dauguet Nicolas , Loriot Axelle , Achouri Younes , Hollmén Maija , Jalkanen Sirpa , Huaux François , Lucas Sophie , Meerkeeck Pierre Van , Knauf Jeffrey A. , Fagin James A. , Dessy Chantal , Mourad Michel , Henriet Patrick , Tyteca Donatienne , Marbaix Etienne , Pierreux Christophe E.
Published: September 2022

Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers (TC), and BRAFV600E genetic alteration is found in 60% of this endocrine cancer. This oncogene is associated with poor prognosis, resistance to radioiodine therapy, and tumor progression. Histological follow-up by anatomo-pathologists revealed that two-thirds of surgically-removed thyroids do not present malignant lesions. Thus, continued fundamental research into the molecular mechanisms of TC downstream of BRAFV600E remains central to better understanding the clinical behavior of these tumors. To study PTC, we used a mouse model in which expression of BRAFV600E was specifically switched on in thyrocytes by doxycycline administration. Upon daily intraperitoneal doxycycline injection, thyroid tissue rapidly acquired histological features mimicking human PTC. Transcriptomic analysis revealed major changes in immune signaling pathways upon BRAFV600E induction. Multiplex immunofluorescence confirmed the abundant recruitment of macrophages, among which a population of LYVE-1+/CD206+/STABILIN-1+ was dramatically increased. By genetically inactivating the gene coding for the scavenger receptor STABILIN-1, we showed an increase of CD8+ T cells in this in situ BRAFV600E-dependent TC. Lastly, we demonstrated the presence of CD206+/STABILIN-1+ macrophages in human thyroid pathologies. Altogether, we revealed the recruitment of immunosuppressive STABILIN-1 macrophages in a PTC mouse model and the interest to further study this macrophage subpopulation in human thyroid tissues.
Diagnostic and Therapeutic Strategy in Anaplastic (Malignant) Meningioma, CNS WHO Grade 3
Authors: Di Nunno Vincenzo , Giannini Caterina , Asioli Sofia , Conti Alfredo , Furtner Julia , Balestrini Damiano , Tosoni Alicia
Published: September 2022

Background: Meningiomas are the most common primary central nervous system malignancies accounting for 36% of all intracranial tumors. However, only 1% of meningioma is classified as malignant (anaplastic) meningioma. Due to their rarity, clinical management of these tumors presents several gaps. Methods: We carried out a narrative review aimed to investigate current knowledge of anaplastic meningioma focusing on their pathological and radiological diagnosis, molecular assessment, and loco-regional and systemic management. Results: The most frequent genetic alteration occurring in meningioma is the inactivation in the neurofibromatosis 2 genes (merlin). The accumulation of copy number losses, including 1p, 6p/q, 10q, 14q, and 18p/q, and less frequently 2p/q, 3p, 4p/q, 7p, 8p/q, and 9p, compatible with instability, is restricted to NF2 mutated meningioma. Surgery and different RT approaches represent the milestone of grade 3 meningioma management, while there is a marginal role of systemic therapy. Conclusions: Anaplastic meningiomas are rare tumors, and diagnosis should be suspected and confirmed by trained radiologists and pathologists. Despite the current marginal role of systemic therapy, it is possible that the increasing knowledge of molecular altered pathways of the disease will lead to the development of novel effective systemic treatments.
Identification and Validation of a Novel Ferroptotic Prognostic Genes-Based Signature of Clear Cell Renal Cell Carcinoma
Authors: Shi Zhiyuan , Zheng Jianzhong , Liang Qing , Liu Yankuo , Yang Yi , Wang Rui , Wang Mingshan , Zhang Qian , Xuan Zuodong , Sun Huimin , Wang Kejia , Shao Chen
Published: September 2022

Renal cell carcinoma (RCC), as one of the primary urological malignant neoplasms, shows poor survival, and the leading pathological type of RCC is clear cell RCC (ccRCC). Differing from other cell deaths (such as apoptosis, necroptosis, pyroptosis, and autophagy), ferroptosis is characterized by iron-dependence, polyunsaturated fatty acid oxidization, and lipid peroxide accumulation. We analyzed the ferroptosis database (FerrDb V2), Gene Expression Omnibus database, The Cancer Genome Atlas database, and the ArrayExpress database. Nine genes that were differentially expressed and related to prognosis were involved in the ferroptotic prognostic model via the least absolute shrinkage and selection operator Cox regression analysis, which was established in ccRCC patients from the kidney renal clear cell carcinoma (KIRC) cohort in TCGA database, and validated in ccRCC patients from the E-MTAB-1980 cohort in the ArrayExpress database. The signature could be an independent prognostic factor for ccRCC, and high-risk patients showed worse overall survival. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were utilized to investigate the potential mechanisms. The nine genes in ccRCC cells with erastin or RSL3 treatment were validated to find the crucial gene. The glutaminase 2 (GLS2) gene was upregulated during ferroptosis in ccRCC cells, and cells with GLS2 shRNA displayed lower survival, a lower glutathione level, and a high lipid peroxide level, which illustrated that GLS2 might be a ferroptotic suppressor in ccRCC.
Evaluation of the Synergistic Potential of Simultaneous Pan- or Isoform-Specific BET and SYK Inhibition in B-Cell Lymphoma: An In Vitro Approach
Authors: Sender Sina , Sultan Ahmad Wael , Palmer Daniel , Koczan Dirk , Sekora Anett , Beck Julia , Schuetz Ekkehard , Taher Leila , Brenig Bertram , Fuellen Georg , Junghanss Christian , Murua Escobar Hugo
Published: September 2022

Background: Both bromodomain and extra-terminal domain (BET) proteins and spleen tyrosine kinase (SYK) represent promising targets in diffuse large B-cell (DLBCL) and Burkitt’s lymphoma (BL). We evaluated the anti-lymphoma activity of the isoform-specific bivalent BET inhibitor AZD5153 (AZD) and the pan-BET inhibitor I-BET151 (I-BET) as single agents and in combination with SYK inhibitor Entospletinib (Ento) in vitro. Methods: The effect of the single agents on cell proliferation and metabolic activity was evaluated in two DLBCL and two BL cell lines. Proliferation, metabolic activity, apoptosis, cell cycle and morphology were further investigated after a combined treatment of AZD or I-BET and Ento. RNAseq profiling of combined AZD+Ento treatment was performed in SU-DHL-4 cells. Results: Both BET inhibitors reduced cell proliferation and metabolic activity in a dose- and time-dependent manner. Combined BET and SYK inhibition enhanced the anti-proliferative effect and induced a G0/G1 cell cycle arrest. SU-DHL-4 demonstrated a pronounced modulation of gene expression by AZD, which was markedly increased by additional SYK inhibition. Functional enrichment analyses identified combination-specific GO terms related to DNA replication and cell division. Genes such as ADGRA2, MYB, TNFRSF11A, S100A10, PLEKHH3, DHRS2 and FOXP1-AS1 were identified as possible key regulators. Conclusion: Simultaneous inhibition of BET and SYK enhanced the anti-proliferative effects, and induced a combination-specific gene expression signature.
FOXA1 in Breast Cancer: A Luminal Marker with Promising Prognostic and Predictive Impact
Authors: Metovic Jasna , Borella Fulvio , D’Alonzo Marta , Biglia Nicoletta , Mangherini Luca , Tampieri Cristian , Bertero Luca , Cassoni Paola , Castellano Isabella
Published: September 2022

The present review focuses on the function of the forkhead protein FOXA1 in breast cancer (BC) in relation to steroid hormone receptors. We explored the currently available analytic approaches for FOXA1 assessment both at gene and protein levels, comparing the differences between the available techniques used for its diagnostic assessment. In addition, we elaborated on data regarding the prognostic and predictive role of this marker in BC based on several studies that evaluated its expression in relation to the outcome and/or response to therapy. FOXA1, similar to the androgen receptor (AR), may have a dual role in BC according to hormonal status. In luminal cancers, its expression contributes to a better prognosis, while in triple-negative breast cancers (TNBC), it implies an adverse outcome. Consequently, we observed that FOXA1-positive expression in a neoadjuvant setting may predict a lack of response in luminal BC as opposed to TNBC, in which FOXA1 allegedly increases its chemosensitivity. In conclusion, considering its accessible and convenient identification by immunohistochemistry, its important impact on prognosis, and its suitability to identify patients with different responses to chemotherapy, we propose that FOXA1 could be tested in routine diagnostics as an additional prognostic and predictive marker in BC.
Metabolic Imaging in B-Cell Lymphomas during CAR-T Cell Therapy
Authors: Linguanti Flavia , Abenavoli Elisabetta Maria , Berti Valentina , Lopci Egesta
Published: September 2022

Chimeric antigen receptor–engineered (CAR) T cells are emerging powerful therapies for patients with refractory/relapsed B-cell lymphomas. [18F]FDG PET/CT plays a key role during staging and response assessment in patients with lymphoma; however, the evidence about its utility in CAR-T therapies for lymphomas is limited. This review article aims to provide an overview of the role of PET/CT during CAR-T cell therapy in B-cell lymphomas, focusing on the prognostic value of metabolic parameters, as well as on response assessment. Data from the literature report on the use of [18F]FDG PET/CT at the baseline with two scans performed before treatment started focused on the time of decision (TD) PET/CT and time of transfusion (TT) PET/CT. Metabolic tumor burden is the most studied parameter associated with disease progression and overall survival, making us able to predict the occurrence of adverse effects. Instead, for post-therapy evaluation, 1 month (M1) PET/CT seems the preferable time slot for response assessment and in this setting, the Deauville 5-point scale (DS), volumetric analyses, SUVmax, and its variation between different time points (∆SUVmax) have been evaluated, confirming the usefulness of M1 PET/CT, especially in the case of pseudoprogression. Additionally, an emerging role of PET/CT brain scans is reported for the evaluation of neurotoxicity related to CAR-T therapies. Overall, PET/CT results to be an accurate method in all phases of CAR-T treatment, with particular interest in assessing treatment response. Moreover, PET parameters have been reported to be reliable predictors of outcome and severe toxicity.
The KEAP1-NRF2 System and Esophageal Cancer
Authors: Hirose Wataru , Oshikiri Hiroyuki , Taguchi Keiko , Yamamoto Masayuki
Published: September 2022

NRF2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates the expression of many cytoprotective genes. NRF2 activation is mainly regulated by KEAP1 (kelch-like ECH-associated protein 1) through ubiquitination and proteasome degradation. Esophageal cancer is classified histologically into two major types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC harbors more genetic alterations in the KEAP-NRF2 system than EAC does, which results in NRF2 activation in these cancers. NRF2-addicted ESCC exhibits increased malignancy and acquisition of resistance to chemoradiotherapy. Therefore, it has been recognized that the development of drugs targeting the KEAP1-NRF2 system based on the molecular dissection of NRF2 function is important and urgent for the treatment of ESCC, along with efficient clinical screening for NRF2-addicted ESCC patients. Recently, the fate of NRF2-activated cells in esophageal tissues, which was under the influence of strong cell competition, and its relationship to the pathogenesis of ESCC, was clarified. In this review, we will summarize the current knowledge of the KEAP1-NRF2 system and the treatment of ESCC. We propose three main strategies for the treatment of NRF2-addicted cancer: (1) NRF2 inhibitors, (2) synthetic lethal drugs for NRF2-addicted cancers, and (3) NRF2 inducers of the host defense system.
Expression of MUC16/CA125 Is Associated with Impaired Survival in Patients with Surgically Resected Cholangiocarcinoma
Authors: Kinzler Maximilian N. , Schulze Falko , Gretser Steffen , Abedin Nada , Trojan Jörg , Zeuzem Stefan , Schnitzbauer Andreas A. , Walter Dirk , Wild Peter J. , Bankov Katrin
Published: September 2022

MUC16/CA125 is associated with cancer proliferation in several tumor entities. The data on MUC16 expression in cholangiocarcinoma (CCA) tissue are very limited. The aim of this study was to assess the MUC16 status and its impact on survival in CCA patients. All the patients with surgically resected CCA that were diagnosed between August 2005 and December 2021 at the University Hospital Frankfurt were retrospectively analyzed. A 7-Mucin biomarker panel was assessed by immunohistochemistry. For overall survival (OS), Kaplan–Meier curves and Cox-regression analyses were performed. Randomly selected intrahepatic cholangiocarcinoma (iCCA) were further processed for differential expression profiling. A total of 168 patients with CCA were classified as MUC16 (−) (66%, n = 111) and MUC16 (+) (34%, n = 57). Subgroup analyses revealed a median OS of 56.1 months (95% CI = 42.4–69.9 months) and 27.4 months (95% CI = 15.8–39.1 months) for MUC16 (−) and MUC16 (+), respectively (p < 0.001). In multivariate analysis, MUC16 (+) (HR = 1.6, 95% CI = 1–2.6, p = 0.032) was an independent risk factor for poor prognosis. Prominently deregulated pathways have been identified following MUC16 expression, overrepresented in cell cycle and immune system exhaustion processes. These findings suggest including MUC16 in clinical routine diagnostics as well as studying its molecular pathways to identify further mechanistic key players.
Clinical and Sociodemographic Determinants of Adherence to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Recommendations in Breast Cancer Survivors—Health-EpiGEICAM Study
Authors: Lope Virginia , Guerrero-Zotano Angel , Ruiz-Moreno Emma , Bermejo Begoña , Antolín Silvia , Montaño Álvaro , Baena-Cañada José Manuel , Ramos Vázquez Manuel , Fernández de Larrea-Baz Nerea , Chacón José Ignacio , García-Sáenz José Angel , Olier Clara , Muñoz Montserrat , Antón Antonio , Sánchez Rovira Pedro , Arcusa Lanza Angels , González Sonia , Oltra Amparo , Brunet Joan , Gavilá Gregori Joaquín , Martínez María Teresa , Calvo Lourdes , Rosell Libertad , Bezares Susana , Pastor-Barriuso Roberto , Pérez-Gómez Beatriz , Martín Miguel , Pollán Marina
Published: September 2022

Breast cancer (BC) survivors are advised to follow the WCRF/AICR cancer prevention recommendations, given their high risk of developing a second tumour. We aimed to explore compliance with these recommendations in BC survivors and to identify potentially associated clinical and sociodemographic factors. A total of 420 BC survivors, aged 31–80, was recruited from 16 Spanish hospitals. Epidemiological, dietary and physical activity information was collected through questionnaires. A 7-item score to measure compliance with the recommendations was built according to the 2018 WCRF/AICR scoring criteria. Standardized prevalences and standardized prevalence ratios of moderate and high compliance across participant characteristics were estimated using multinomial and binary logistic regression models. The mean score was 3.9 (SD: 1.0) out of 7 points. Recommendations with the worst adherence were those of limiting consumption of red/processed meats (12% of compliance, 95% CI: 8.2–15.0) and high fibre intake (22% of compliance, 95% CI: 17.6–27.0), while the best compliance was observed for the consumption of fruits and vegetables (73% of compliance, 95% CI: 69.2–77.7). Overall, adherence was worse in women with university education and in those with first-degree relatives with BC. This information may be of interest to design and implement personalized preventive measures adapted to the characteristics of these patients.
Histone Deacetylase Inhibitors as a Therapeutic Strategy to Eliminate Neoplastic “Stromal” Cells from Giant Cell Tumors of Bone
Authors: Venneker Sanne , van Eenige Robin , Kruisselbrink Alwine B. , Palubeckaitė Ieva , Taliento Alice E. , Briaire-de Bruijn Inge H. , Hogendoorn Pancras C. W. , van de Sande Michiel A. J. , Gelderblom Hans , Mei Hailiang , Bovée Judith V. M. G. , Szuhai Karoly
Published: September 2022

The neoplastic “stromal” cells in giant cell tumor of bone (GCTB) harbor a mutation in the H3F3A gene, which causes alterations in the epigenome. Current systemic targeted therapies, such as denosumab, do not affect the neoplastic cells, resulting in relapse upon treatment discontinuation. Therefore, this study examined whether targeting the epigenome could eliminate the neoplastic cells from GCTB. We established four novel cell lines of neoplastic “stromal” cells that expressed the H3F3A p.G34W mutation. These cell lines were used to perform an epigenetics compound screen (n = 128), which identified histone deacetylase (HDAC) inhibitors as key epigenetic regulators in the neoplastic cells. Transcriptome analysis revealed that the neoplastic cells expressed all HDAC isoforms, except for HDAC4. Therefore, five HDAC inhibitors targeting different HDAC subtypes were selected for further studies. All GCTB cell lines were very sensitive to HDAC inhibition in both 2D and 3D in vitro models, and inductions in histone acetylation, as well as apoptosis, were observed. Thus, HDAC inhibition may represent a promising therapeutic strategy to eliminate the neoplastic cells from GCTB lesions, which remains the paramount objective for GCTB patients who require life-long treatment with denosumab.
Fasudil Increased the Sensitivity to Gefitinib in NSCLC by Decreasing Intracellular Lipid Accumulation
Authors: Liao Tingting , Deng Jingjing , Chen Wenjuan , Xu Juanjuan , Yang Guanghai , Zhou Mei , Lv Zhilei , Wang Sufei , Song Siwei , Tan Xueyun , Yin Zhengrong , Li Yumei , Jin Yang
Published: September 2022

Tyrosine kinase inhibitors (TKIs) resistance is a challenge in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Here, we examined the effect of Fasudil in reversing TKIs resistance. The results of CCK8 assay, clone formation assay, cell cycle arrest analysis, and apoptosis analysis show that Fasudil treatment effectively suppressed the growth and induced apoptosis of the EGFR-mutant NSCLC cells. Furthermore, Fasudil in combination with gefitinib showed a synergistic anti-tumor effect in gefitinib-resistant NSCLC cells. RNA-seq analysis and immunoblotting indicated that Fasudil treatment significantly inhibited intracellular lipid accumulation and EGFR/PI3K/AKT pathway activation. Mechanistic investigations showed that Fasudil regulated lipogenic gene expressions via AMPK signal pathway. In vivo, Fasudil and gefitinib co-administration significantly attenuated the growth of H1975 nude mouse xenograft models, suggesting that Fasudil treatment combined with gefitinib can be applied as a therapy for gefitinib-resistant NSCLC cells.
A Highly Active NiMoAl Catalyst Prepared by a Solvothermal Method for the Hydrogenation of Methyl Acrylate
Authors: Sun Taolue , Wang Gang , Guo Xinpeng , Li Zengxi , Wang Erqiang , Li Chunshan
Published: September 2022

In this study, a series of Ni10MoxAl composite metal oxide (Ni10MoxAl, NiO = 10 wt.%, x = 2.5, 5, 10, 15, 20 wt.%) catalysts with different Mo content were prepared by a solvothermal method using a water—ethanol system. By employing various characterization technologies, it was confirmed that the suitable amount of the Mo element can not only promote the dispersion of the Ni species but also inhibit the formation of the inactive NiAl2O4 phase. Consequently, the hydrogenation activity of the Ni10MoxAl catalysts was affected by the particle size of the active components and the amount of the NiAl2O4 phase. As a result, the Ni10Mo10Al catalyst showed the best catalytic performance on methyl acrylate hydrogenation, and the yield of methyl propionate can be increased from 53.7% to 89.5% at 100 °C and 1 MP H2, compared with the Ni10Mo10/γ–Al2O3 catalyst prepared by a traditional impregnation method. The stability of the Ni10Mo10Al catalyst was also investigated, and the catalyst can run stably for 23 h. The novel strategy adopted in this article provides a new direction for the preparation of high activity Ni–Mo catalysts.
Cerium-Doped CoMn2O4 Spinels as Highly Efficient Bifunctional Electrocatalysts for ORR/OER Reactions
Authors: Chen Xiao , Han Fengshuang , Chen Xi , Zhang Chenxi , Gou Wangyan
Published: September 2022

Low-cost and highly efficient electrocatalysts for oxygen reactions are highly important for oxygen-related energy storage/conversion devices (e.g., solar fuels, fuel cells, and rechargeable metal-air batteries). In this work, a range of compositionally-tuned cerium-doped CoMn2O4 (Ce-CMO-X) spinels were prepared via oxidizing precipitation and subsequent crystallization method and evaluated as electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The Ce modification into the CMO spinels lead to the changes of surface electronic structure. And Ce-CMO-X catalysts display better electrochemical performance than that of pristine CMO spinel. Among them, Ce-CMO-18% shows the best activity. The Ce-CMO-18% processes a higher ratio of Co3+/Co2+, Mn4+/Mn3+, which is beneficial to ORR performance, while the higher content of oxygen vacancies in Ce-CMO-18% make for better OER performance. Thus, the Ce-doped CMO spinels are potential candidates as bifunctional electrocatalysts for both ORR and OER in alkaline environments. Then, the hybrid Ce-CMO-18%/MWCNTs catalyst was also synthesized, which shows further enhanced ORR and OER activities. It displays an ORR onset potential of 0.93 V and potential of 0.84 V at density of 3 mA cm−2 (at 1600 rpm), which is comparable to commercial Pt/C. The OER onset potential and potential at a current density 10 mA cm-2 are 183 mV and 341 mV. The superior electrical conductivity and oxygen functional groups at the surface of MWCNTs can facilitate the interaction between metal oxides and carbon, which promoted the OER and ORR performances significantly.
The Recent Advances in Bulk and Microfluidic-Based pH Sensing and Its Applications
Authors: Xiao Weiyu , Dong Qiuchen
Published: September 2022

The determination of pH is of paramount importance in environmental, pharmaceutical, and medicinal sciences, etc., for accurate controlling, monitoring, and adjusting whole processes on microscale and macroscale. Therefore, the pH measurements have drawn continuous efforts from a great deal of research. The bulk pH determination can tackle part of the demands from laboratories and industrial applications. However, more and more studies have started to pay more attention to microfluidic-based pH sensing by integrating with metal oxides and solid-state-based pH sensing applications. This review paper focuses on the recent development of pH sensing, the mechanisms of pH sensing, a few common pH sensors, and microfluidic-based pH determinations from the aspects of fabrication techniques to the various applications in biology, environmental study, and food safety. The future trends of pH sensing, as well as microfluidic-based pH sensing, were discussed as well at the end of this review.
MgrB Mutations and Altered Cell Permeability in Colistin Resistance in Klebsiella pneumoniae
Authors: Yap Polly Soo-Xi , Cheng Wan-Hee , Chang Sook-Keng , Lim Swee-Hua Erin , Lai Kok-Song
Published: September 2022

There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation.
Shining Light on Autophagy in Skin Pigmentation and Pigmentary Disorders
Authors: Kovacs Daniela , Cardinali Giorgia , Picardo Mauro , Bastonini Emanuela
Published: September 2022

Autophagy is a vital process for cell survival and it preserves homeostasis by recycling or disassembling unnecessary or dysfunctional cellular constituents. Autophagy ameliorates skin integrity, regulating epidermal differentiation and constitutive pigmentation. It induces melanogenesis and contributes to skin color through melanosome turnover. Autophagy activity is involved in skin phenotypic plasticity and cell function maintenance and, if altered, it concurs to the onset and/or progression of hypopigmentary and hyperpigmentary disorders. Overexpression of autophagy exerts a protective role against the intrinsic metabolic stress occurring in vitiligo skin, while its dysfunction has been linked to the tuberous sclerosis complex hypopigmentation. Again, autophagy impairment reduces melanosome degradation by concurring to pigment accumulation characterizing senile lentigo and melasma. Here we provide an updated review that describes recent findings on the crucial role of autophagy in skin pigmentation, thus revealing the complex interplay among melanocyte biology, skin environment and autophagy. Hence, targeting this process may also represent a promising strategy for treating pigmentary disorders.
Metabolomics in Diabetic Retinopathy: From Potential Biomarkers to Molecular Basis of Oxidative Stress
Authors: Jian Qizhi , Wu Yingjie , Zhang Fang
Published: September 2022

Diabetic retinopathy (DR), the leading cause of blindness in working-age adults, is one of the most common complications of diabetes mellitus (DM) featured by metabolic disorders. With the global prevalence of diabetes, the incidence of DR is expected to increase. Prompt detection and the targeting of anti-oxidative stress intervention could effectively reduce visual impairment caused by DR. However, the diagnosis and treatment of DR is often delayed due to the absence of obvious signs of retina imaging. Research progress supports that metabolomics is a powerful tool to discover potential diagnostic biomarkers and therapeutic targets for the causes of oxidative stress through profiling metabolites in diseases, which provides great opportunities for DR with metabolic heterogeneity. Thus, this review summarizes the latest advances in metabolomics in DR, as well as potential diagnostic biomarkers, and predicts molecular targets through the integration of genome-wide association studies (GWAS) with metabolomics. Metabolomics provides potential biomarkers, molecular targets and therapeutic strategies for controlling the progress of DR, especially the interventions at early stages and precise treatments based on individual patient variations.
Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis
Authors: Romero Yair , Balderas-Martínez Yalbi Itzel , Vargas-Morales Miguel Angel , Castillejos-López Manuel , Vázquez-Pérez Joel Armando , Calyeca Jazmín , Torres-Espíndola Luz María , Patiño Nelly , Camarena Angel , Carlos-Reyes Ángeles , Flores-Soto Edgar , León-Reyes Guadalupe , Sierra-Vargas Martha Patricia , Herrera Iliana , Luis-García Erika Rubí , Ruiz Víctor , Velázquez-Cruz Rafael , Aquino-Gálvez Arnoldo
Published: September 2022

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control′s response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.