bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of Micro-Scale Built Environment Features on Tourists’ Walking Behaviors in Historic Streets: Insights from Wudaoying Hutong, China
Authors: Xu Gaofeng , Zhong Le , Wu Fei , Zhang Yin , Zhang Zhenwei
Published: December 2022

The impact of built environment features on tourists’ walking behaviors has received growing attention. Although many researchers have observed the effects of micro-scale factors, the impact of culture-related factors on walking behaviors has been frequently overlooked. Therefore, it is vital to synthesize those micro-scale variables to develop a more holistic picture, and incorporating a cultural perspective is an imperative for the preservation and vitality enhancement of historic streets. In our study, a micro-scale built environment (MiBE) variable system was constructed to capture the features of historic streets, and 109 visitors were tracked in Wudaoying Hutong to record their walking-stopping behaviors. The results revealed four primary components affecting walking-stopping behaviors, among which transparency was the most influential factor, followed by the transitional space between streets and buildings, contributing to 49.8% and 21.6%, respectively. Notably, the non-negligible impact of two culture-related factors, including the contrast between Chinese and Western styles and traditional Chinese features, was also revealed, contributing to 28.6% of the total observed activities. We further compared four different types of micro-scale factors of the built environment and the corresponding walking-stopping behaviors, providing both scientific and theoretical reflections for preserving and renewing historic streets.
Collaborative Evolution Mechanism and Simulation of Construction Waste Recycling Stakeholders Based on Social Network
Authors: Shao Zhiguo , Li Mengdi , Yu Dehu , Han Chuanfeng , Meng Lingpeng
Published: December 2022

With the continuous advancement of urbanization, a huge amount of construction waste is generated in large-scale construction activities, which has aggravated the problems of environmental pollution, waste of resources and destruction of city appearance. Construction waste recycling can effectively solve these problems. However, the recycling rate of construction waste is low in China. Therefore, this paper, firstly through the way of literature analysis and questionnaire investigation, analyzes the factors that influence construction waste resource utilization, determines the key influence factors and the stakeholders in the process of construction waste resource utilization, and uses social network analysis method to identify core stakeholders. On this basis, this paper selects construction enterprises and recycling enterprises as the game subjects, and the government and the public as the external environment to explore the influence of the external environment on the cooperation behavior of the two stakeholders, and uses Matlab simulation to analyze the influence of external variables on the decision-making behavior evolution of the two stakeholders. The research results show that the government, construction enterprises, recycling enterprises and the public are the four core stakeholders of the construction waste recycling system, which have the power to control the information transmission among other stakeholders and play a great supporting role in the smooth implementation of the construction waste recycling project. Among them, the construction enterprise and recycling enterprise are the construction waste recycling system’s two stakeholders playing the pivotal role, and the government and the public are the external environment of the construction waste recycling system’s incentive and regulatory effect. The difference between the benefits and costs of the two stakeholders and the effect intensity of the external environment determines the stable state of the system, that is, the stronger the effect of the external environment and the larger the difference, the more the behavior of the two tends toward the recycling, on-site recycling strategy. Government penalties and rewards can effectively reduce the illegal dumping of construction waste, while excessive penalties and rewards have limitations in controlling illegal dumping. Public participation can effectively improve the efficiency of government supervision. The research results help to deeply understand the behavior, needs and cooperation of stakeholders in the construction waste recycling market, improve the efficiency of cooperation between construction enterprises and recycling enterprises, and provide management inspiration for the construction waste recycling practice.
Corrosion-Induced Cracking Pattern Analysis of RC Beam under Sustained Load Considering the Poromechanical Characteristics of Corrosion Products
Authors: Zeng Bin , Wang Yuzhou , Gong Fuyuan , Maekawa Koichi
Published: December 2022

Concrete cracking is the significant stage of RC structural deterioration induced by steel corrosion. To predict the corrosion-induced cracking of the loaded RC structure, a multi-scale model is proposed. The formation and transport of corrosion products, which affect the volumetric expansion at the steel–concrete interface, are considered in this model. Then, based on poro-mechanics, the calculation of corrosion-induced stress in the pore structure of concrete is enabled. The corrosion-induced cracking of the practical component obtained from the proposed model shows a satisfactory agreement with the experimental observations. Then, the corrosion-induced cracking under different loading conditions are investigated. The results show that the effect of external loads on the time-to-cracking is moderate; the steel corrosion varies by no more 9% under different loading conditions at the surface cracking moment, whereas significant effects of the loading condition on the cracking pattern of reinforced concrete beams are found. Furthermore, the higher the load level, the more rapidly the corrosion-induced cracks develop; the maximum corrosion-induced crack widths on the surface of the beam subjected to 60% ultimate load is 1.14 and 1.22 times that of the 30% and 0% loaded beams, respectively, when reaching the serviceability limit state.
Compressive Behavior of Interlocking Plastic Blocks Structural Elements Having Slenderness
Authors: Adnan Muhammad , Khalid Faiza , Ali Majid
Published: December 2022

Earthquakes are among of the most harmful and potentially fatal natural disasters. Masonry structures in seismic zones of urban and rural areas around the world pose a threat to human life. Housing that is both affordable and earthquake-resistant in earthquake-prone areas is currently in demand in developing countries. For affordable earthquake-resistant structures in earthquake-prone areas, numerous researchers have studied mortar-free interlocking structures. Plastic blocks are used in order to reduce the mass of the overall structure. To start with, structures under gravity are explored first because more than 95% of its design life, any structure has to withstand gravity. Prototypes of interlocking plastic-block columns, solid walls, and walls with an opening are considered for making the mortar-free structures. In this study, the effect of slenderness on the behavior of interlocking-plastic-block structural elements is investigated under compressive loading by a servo-hydraulic testing machine in the laboratory. The effect of slenderness on the behavior of one and two-block-wide structural elements was investigated in terms of the stress–strain curve, energy absorption, and toughness index under compressive loadings. Correlations between the compressive strength of interlocking-plastic-block structural elements with varying thicknesses were found. Scaled-down prototypes of interlocking-plastic-block structural elements having two-block wide depicted more resistance to compressive loads than one block wide structural elements. The correlations among the one and two block wide interlocking-plastic-block columns, single and double-block-wide solid walls, and single and double-block-width walls with an opening found in this analysis were Pdc = 2.2 Psc, Pdsw = 2.9 Pssw, and Pdwo = 3.5 Pswo. This study can be applied in the future to better understand the detailed behavior of interlocking plastic blocks.
Post-Earthquake Condition Assessment and Seismic Upgrading Strategies for a Heritage-Protected School in Petrinja, Croatia
Authors: Salaman Aida , Stepinac Mislav , Matorić Ivan , Klasić Mija
Published: December 2022

Following the Zagreb earthquake in March of 2020, a destructive 6.2 magnitude earthquake struck Croatia again in December of 2020. The Sisak-Moslavina county suffered the most severe consequences; many historical and cultural buildings were badly damaged. In the education sector, 109 buildings were damaged. One such building is the case study of this research. The heritage-protected building of the First Primary School in Petrinja is an unreinforced masonry structure, constructed using traditional materials and building techniques. The historical background of the building and the results of the post-earthquake assessment are presented. A numerical calculation of three strengthening methods was performed in 3Muri software: FRCM, FRP, and shotcrete. Non-linear pushover analysis was performed for each model. Finally, the strengthening methods are compared based on the achieved earthquake capacity, cost, and environmental impact.
Computational Optimization of 3D-Printed Concrete Walls for Improved Building Thermal Performance
Authors: AlZahrani Abdullah A. , Alghamdi Abdulrahman A. , Basalah Ahmad A.
Published: December 2022

Three-dimensional printing technologies are transforming various sectors with promising technological abilities and economic outcomes. For instance, 3D-printed concrete (3DPC) is revolutionizing the construction sector with a promise to cut projects’ costs and time. Therefore, 3DPC has been subjected to extensive research and development to optimize the mechanical and thermal performance of concrete walls produced by 3D printing. In this paper, we conduct a comparative investigation of the thermal performance of various infill structures of 3DPC walls. The targeted outcome is to produce an infill structure with optimized thermal performance to reduce building energy consumption without incurring additional material costs. Accordingly, a computational model is developed to simulate the thermal behavior of various infill structures that can be used for 3DPC walls. The concrete composition and the concrete-to-void fraction are maintained constant to focus on the impact of the infill structure (geometric variations). The thermal performance and energy-saving potential of the 3DPC walls are compared with conventional construction materials, including clay and concrete bricks. The results show that changing the infill structure of the 3DPC walls influences the walls’ thermal conductivity and, thereby, the building’s thermal performance. The thermal conductivity of the examined infill structures is found to vary between 0.122 to 0.17 W/m.K, while if these structures are successful in replacing conventional building materials, the minimum annual saving in energy cost will be about $1/m2. Therefore, selecting an infill structure can be essential for reducing building energy consumption.
Retrospective Cohort Study of Practical Applications of Paramagnetic Seed Localisation in Breast Carcinoma and Other Malignancies
Authors: Clement Céline , Schops Lieve , Nevelsteen Ines , Thijssen Soetkin , Van Ongeval Chantal , Keupers Machteld , Prevos Renate , Celis Valerie , Neven Patrick , Han Sileny , Laenen Annouschka , Smeets Ann
Published: December 2022

(1) Background: Paramagnetic seeds are a safe alternative for the wire-guided localisation of non-palpable breast lesions, but can also be applied for non-breast lesions. This study presents the experience with a paramagnetic seed, MagSeed® (Endomagnetics Ltd., Cambridge, UK, CE-registered and FDA-cleared), in an academic and non-academic breast centre. (2) Methods: Multicentre, retrospective analysis of 374 consecutive patients who underwent surgery after paramagnetic seed localisation (MSL) between 2018 and 2020. Indications for localisation included non-palpable breast lesions (n = 356), lymph nodes (n = 15) or soft tissue lesions (n = 3). The primary outcome was feasibility and the rate of positive section margins. The secondary outcome was predictive factors for positive section margins. (3) Results: The accurate excision of high-risk breast lesions, lymph nodes and soft tissue lesions was seen in 91.07% (n = 56). Positive section margins were observed in 7.86% (n = 25) after breast conserving surgery for invasive or ductal carcinoma in situ (DCIS) (n = 318). Invasive breast cancer associated with DCIS (p = 0.043) and the size of DCIS (p < 0.001) were significantly correlated with the positive section margins. (4) Conclusion: This study confirms the feasibility of MSL, as well as the higher risk for positive margins in cases of breast carcinoma with associated DCIS. Soft tissue lesions and lymph nodes associated with other malignancies, e.g., melanoma, can also be localised with paramagnetic seeds. This offers perspectives for future applications, such as the de-escalation of axillary treatment in breast cancer.
Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma
Authors: Fotiou Despina , Dimopoulos Meletios Athanasios , Kastritis Efstathios
Published: December 2022

Multiple myeloma (MM) is associated with an increased risk of thrombotic complications, which remains substantial despite the implementation of thromboprophylaxis. The procoagulant state that characterizes the disease is multifactorial, and a greater understanding of the underlying pathophysiology is required to inform appropriate thrombosis prevention. Currently, there is a shift towards using direct oral anticoagulants (DOACs) in this setting; head-to-head comparisons in the context of controlled clinical trials between class agents are still missing. MM-specific VTE risk assessment scores have been developed to optimize management and minimize the associated mortality/morbidity. Their clinical utility remains to be evaluated. The value of adding biomarkers to clinical scores to optimize their performance and increase their discriminatory power is also under assessment.
The Lymphatic System, Lymphoedema, and Medical Curricula–Survey of Australian Medical Graduates
Authors: Kruger Natalie , Plinsinga Melanie L. , Noble-Jones Rhian , Piller Neil , Keeley Vaughan , Hayes Sandra C.
Published: December 2022

The aim of this study was to survey the perceptions of recent (i.e., within the past 12 months) Australian medical graduates regarding (i) their understanding of the lymphatic system and lymphoedema, and (ii) the extent to which the lymphatic system and lymphoedema were covered as part of their medical degree. Medical graduates were invited to participate in a 17-item online survey that asked respondents to rate their level of agreement (using a 5-point Likert scale; higher scores = higher agreement) to statements that explored their understanding and comprehensiveness of their medical degree. Responses to each item were described using n (%). Subscale scores for understanding and medical degree were computed by summing scores of individual items, described using means (SD) and compared by participant characteristics. Medical graduates (n = 230) perceived their understanding of the lymphatic system and lymphoedema to be low, and comprehensiveness of medical curricula specific to the lymphatic system and lymphoedema to be lacking. Subscale scores did not differ by participant characteristics. Improvement of medical graduates understanding of lymphoedema may facilitate greater awareness of lymphoedema, thus optimizing the timeliness of diagnosis and access to treatment.
CT Radiomics and Whole Genome Sequencing in Patients with Pancreatic Ductal Adenocarcinoma: Predictive Radiogenomics Modeling
Authors: Hinzpeter Ricarda , Kulanthaivelu Roshini , Kohan Andres , Avery Lisa , Pham Nhu-An , Ortega Claudia , Metser Ur , Haider Masoom , Veit-Haibach Patrick
Published: December 2022

We investigate whether computed tomography (CT) derived radiomics may correlate with driver gene mutations in patients with pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, 47 patients (mean age 64 ± 11 years; range: 42–86 years) with PDAC, who were treated surgically and who underwent preoperative CT imaging at our institution were included in the study. Image segmentation and feature extraction was performed semi-automatically with a commonly used open-source software platform. Genomic data from whole genome sequencing (WGS) were collected from our institution’s web-based resource. Two statistical models were then built, in order to evaluate the predictive ability of CT-derived radiomics feature for driver gene mutations in PDAC. 30/47 of all tumor samples harbored 2 or more gene mutations. Overall, 81% of tumor samples demonstrated mutations in KRAS, 68% of samples had alterations in TP53, 26% in SMAD4 and 19% in CDKN2A. Extended statistical analysis revealed acceptable predictive ability for KRAS and TP53 (Youden Index 0.56 and 0.67, respectively) and mild to acceptable predictive signal for SMAD4 and CDKN2A (Youden Index 0.5, respectively). Our study establishes acceptable correlation of radiomics features and driver gene mutations in PDAC, indicating an acceptable prognostication of genomic profiles using CT-derived radiomics. A larger and more homogenous cohort may further enhance the predictive ability.
Correlation between DNA Methylation and Cell Proliferation Identifies New Candidate Predictive Markers in Meningioma
Authors: Hergalant Sébastien , Saurel Chloé , Divoux Marion , Rech Fabien , Pouget Celso , Godfraind Catherine , Rouyer Pierre , Lacomme Stéphanie , Battaglia-Hsu Shyue-Fang , Gauchotte Guillaume
Published: December 2022

Meningiomas are the most common primary tumors of the central nervous system. Based on the 2021 WHO classification, they are classified into three grades reflecting recurrence risk and aggressiveness. However, the WHO’s histopathological criteria defining these grades are somewhat subjective. Together with reliable immunohistochemical proliferation indices, other molecular markers such as those studied with genome-wide epigenetics promise to revamp the current prognostic classification. In this study, 48 meningiomas of various grades were randomly included and explored for DNA methylation with the Infinium MethylationEPIC microarray over 850k CpG sites. We conducted differential and correlative analyses on grade and several proliferation indices and markers, such as mitotic index and Ki-67 or MCM6 immunohistochemistry. We also set up Cox proportional hazard models for extensive associations between CpG methylation and survival. We identified loci highly correlated with cell growth and a targeted methylation signature of regulatory regions persistently associated with proliferation, grade, and survival. Candidate genes under the control of these regions include SMC4, ESRRG, PAX6, DOK7, VAV2, OTX1, and PCDHA-PCDHB-PCDHG, i.e., the protocadherin gene clusters. This study highlights the crucial role played by epigenetic mechanisms in shaping dysregulated cellular proliferation and provides potential biomarkers bearing prognostic and therapeutic value for the clinical management of meningioma.
Hyperthermia as a Potential Cornerstone of Effective Multimodality Treatment with Radiotherapy, Cisplatin and PARP Inhibitor in IDH1-Mutated Cancer Cells
Authors: Khurshed Mohammed , Prades-Sagarra Elia , Saleh Sarah , Sminia Peter , Wilmink Johanna W. , Molenaar Remco J. , Crezee Hans , van Noorden Cornelis J. F.
Published: December 2022

Mutations in the isocitrate dehydrogenase 1 (IDH1MUT) gene occur in various types of malignancies, including ~60% of chondrosarcomas, ~30% of intrahepatic cholangiocarcinomas and >80% of low-grade gliomas. IDH1MUT are causal in the development and progression of these types of cancer due to neomorphic production of the oncometabolite D-2-hydroxyglutarate (D-2HG). Intracellular accumulation of D-2HG has been implicated in suppressing homologous recombination and renders IDH1MUT cancer cells sensitive to DNA-repair-inhibiting agents, such as poly-(adenosine 5′-diphosphate–ribose) polymerase inhibitors (PARPi). Hyperthermia increases the efficacy of DNA-damaging therapies such as radiotherapy and platinum-based chemotherapy, mainly by inhibition of DNA repair. In the current study, we investigated the additional effects of hyperthermia (42 °C for 1 h) in the treatment of IDH1MUT HCT116 colon cancer cells and hyperthermia1080 chondrosarcoma cancer cells in combination with radiation, cisplatin and/or a PARPi on clonogenic cell survival, cell cycle distribution and the induction and repair of DNA double-strand breaks. We found that hyperthermia in combination with radiation or cisplatin induces an increase in double-strand breaks and cell death, up to 10-fold in IDH1MUT cancer cells compared to IDH1 wild-type cells. This vulnerability was abolished by the IDH1MUT inhibitor AGI-5198 and was further increased by the PARPi. In conclusion, our study shows that IDH1MUT cancer cells are sensitized to hyperthermia in combination with irradiation or cisplatin and a PARPi. Therefore, hyperthermia may be an efficacious sensitizer to cytotoxic therapies in tumors where the clinical application of hyperthermia is feasible, such as IDH1MUT chondrosarcoma of the extremities.
Preoperative Cancer Inflammation Prognostic Index as a Superior Predictor of Short- and Long-Term Outcomes in Patients with Stage I–III Colorectal Cancer after Curative Surgery
Authors: You Jeng-Fu , Hsu Yu-Jen , Chern Yih-Jong , Cheng Ching-Chung , Jong Bor-Kang , Liao Chun-Kai , Hsieh Pao-Shiu , Hsu Hung-Chih , Tsai Wen-Sy
Published: December 2022

Inflammatory reactions play a crucial role in cancer progression and may contribute to systemic inflammation. In routine clinical practice, some inflammatory biomarkers can be utilized as valuable predictors for colorectal cancer (CRC). This study aims to determine the usefulness of a novel cancer-inflammation prognostic index (CIPI) marker derived from calculating carcinoembryonic antigen (CEA) multiplied by the neutrophil-to-lymphocyte ratio (NLR) values established for non-metastatic CRCs. Between January 1995 and December 2018, 12,092 patients were diagnosed with stage I to III primary CRC and had radical resection—they were all included in this study for further investigation. There were 5996 (49.6%) patients in the low-CIPI group and 6096 (50.4%) patients in the high-CIPI group according to the cutoff value of 8. For long-term outcomes, the high-CIPI group had a significantly higher incidence of recurrence (30.6% vs. 16.0%, p < 0.001) and worse relapse-free survival (RFS) and overall survival (OS) rates (p < 0.001). High CIPI was an independent prognostic factor for RFS and OS in univariate and multivariate analyses. This research is the first to document the independent significance of CIPI as a prognostic factor for CRC. To ensure that it works, this CIPI needs to be tested on more CRC prediction models.
Quantitative Diffusion-Weighted Imaging Analyses to Predict Response to Neoadjuvant Immunotherapy in Patients with Locally Advanced Head and Neck Carcinoma
Authors: van der Hulst Hedda J. , Vos Joris L. , Tissier Renaud , Smit Laura A. , Martens Roland M. , Beets-Tan Regina G. H. , van den Brekel Michiel W. M. , Zuur Charlotte L. , Castelijns Jonas A.
Published: December 2022

Background: Neoadjuvant immune checkpoint blockade (ICB) prior to surgery may induce early pathological responses in head and neck squamous cell carcinoma (HNSCC) patients. Routine imaging parameters fail to diagnose these responses early on. Magnetic resonance (MR) diffusion-weighted imaging (DWI) has proven to be useful for detecting HNSCC tumor mass after (chemo)radiation therapy. METHODS: 32 patients with stage II–IV, resectable HNSCC, treated at a phase Ib/IIa IMCISION trial (NCT03003637), were retrospectively analyzed using MR-imaging before and after two doses of single agent nivolumab (anti-PD-1) (n = 6) or nivolumab with ipilimumab (anti-CTLA-4) ICB (n = 26). The primary tumors were delineated pre- and post-treatment. A total of 32 features were derived from the delineation and correlated with the tumor regression percentage in the surgical specimen. Results: MR-DWI data was available for 24 of 32 patients. Smaller baseline tumor diameter (p = 0.01−0.04) and higher sphericity (p = 0.03) were predictive of having a good pathological response to ICB. Post-treatment skewness and the change in skewness between MRIs were negatively correlated with the tumor’s regression (p = 0.04, p = 0.02). Conclusion: Pre-treatment DWI tumor diameter and sphericity may be quantitative biomarkers for the prediction of an early pathological response to ICB. Furthermore, our data indicate that ADC skewness could be a marker for individual response evaluation.
Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters
Authors: Karimi Masoud , Osterlund Pia , Hammarström Klara , Imam Israa , Frodin Jan-Erik , Glimelius Bengt
Published: December 2022

Complete pathological response (pCR) is achieved in 10–20% of rectal cancers when treated with short-course radiotherapy (scRT) or long-course chemoradiotherapy (CRT) and in 28% with total neoadjuvant therapy (scRT/CRT + CTX). pCR is associated with better outcomes and a “watch-and-wait” strategy (W&W). The aim of this study was to identify baseline clinical or imaging factors predicting pCR. All patients with preoperative treatment and delays to surgery in Uppsala-Dalarna (n = 359) and Stockholm (n = 635) were included. Comparison of pCR versus non-pCR was performed with binary logistic regression models. Receiver operating characteristics (ROC) models for predicting pCR were built using factors with p < 0.10 in multivariate analyses. A pCR was achieved in 12% of the 994 patients (scRT 8% [33/435], CRT 13% [48/358], scRT/CRT + CTX 21% [43/201]). In univariate and multivariate analyses, choice of CRT (OR 2.62; 95%CI 1.34–5.14, scRT reference) or scRT/CRT + CTX (4.70; 2.23–9.93), cT1–2 (3.37; 1.30–8.78; cT4 reference), tumour length ≤ 3.5 cm (2.27; 1.24–4.18), and CEA ≤ 5 µg/L (1.73; 1.04–2.90) demonstrated significant associations with achievement of pCR. Age < 70 years, time from radiotherapy to surgery > 11 weeks, leucocytes ≤ 109/L, and thrombocytes ≤ 4009/L were significant only in univariate analyses. The associations were not fundamentally different between treatments. A model including T-stage, tumour length, CEA, and leucocytes (with scores of 0, 0.5, or 1 for each factor, maximum 4 points) showed an area under the curve (AUC) of 0.66 (95%CI 0.60–0.71) for all patients, and 0.65–0.73 for the three treatments separately. The choice of neoadjuvant treatment in combination with low CEA, short tumour length, low cT-stage, and normal leucocytes provide support in predicting pCR and, thus, could offer guidance for selecting patients for organ preservation.
Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients
Authors: Vinh-Hung Vincent , Gorobets Olena , Adriaenssens Nele , Van Parijs Hilde , Storme Guy , Verellen Dirk , Nguyen Nam P. , Magne Nicolas , De Ridder Mark
Published: December 2022

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007–2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1–5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007–2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6–4.6 to 4.3–4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.
Predictive Value of 18F-Fluorodeoxyglucose Positron-Emission Tomography Metabolic and Volumetric Parameters for Systemic Metastasis in Tonsillar Cancer
Authors: Bang Jooin , Park Hye Lim , Yoo Ie Ryung , Shin Hyun-Il , Kim Geun-Jeon , Sun Dong-Il , Kim Sang-Yeon
Published: December 2022

Although the prognosis of tonsillar cancer (human papillomavirus-positive oropharyngeal squamous cell carcinoma) is improving, disease control failure (distant metastasis) still occurs in some cases. We explored whether several 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) parameters can predict metastasis. We retrospectively reviewed the medical records of 55 patients with tonsil squamous cell carcinoma who underwent pretreatment 18F-FDG positron-emission tomography/computed tomography (PET/CT) followed by primary surgery. During the follow-up period, systemic metastases were found in 7 of the 55 patients. The most common sites were the lungs (33%), bone (22%), brain/skull base (22%), small bowel (11%), and liver (11%). Pathologically, P53 mutation was less common in patients with systemic metastasis (41.7% vs. 14.3%, p = 0.054) than without systemic metastasis. In terms of PET parameters, the metabolic tumor volume (MTV2.5) and total lesion glycolysis (TLG2.5) values were lower in the primary tumor, and higher in the metastatic lymph nodes, of human papillomavirus (HPV)-positive compared to HPV-negative patients (all p < 0.05). The MTV2.5, TLG2.5, and tumor–to–liver uptake ratio were 36.07 ± 54.24 cm3, 183.46 ± 298.62, and 4.90 ± 2.77, respectively, in the systemic metastasis group, respectively; all of these values were higher than those of the patients without systemic metastasis (all p < 0.05). The MTV2.5 value was significantly different between the groups even when the values for the primary tumor and metastatic lymph nodes were summed (53.53 ± 57.78 cm3, p = 0.036). The cut-off value, area under the curve (95% confidence interval), sensitivity, and specificity of MTV2.5 for predicting systemic metastasis were 11.250 cm3, 0.584 (0.036–0.832), 0.571, and 0.565, respectively. The MTV2.5 of metastatic lymph nodes and summed MTV2.5 values of the primary tumor and metastatic lymph nodes were significantly higher in tonsillar cancer patients with than without systemic metastases. We suggest PET/CT scanning for pre-treatment cancer work-up and post-treatment surveillance to consider additional systemic therapy in patients with a high risk of disease control failure.
The Normal, the Radiosensitive, and the Ataxic in the Era of Precision Radiotherapy: A Narrative Review
Authors: Pereira Sandrine , Orlandi Ester , Deneuve Sophie , Barcellini Amelia , Chalaszczyk Agnieszka , Behm-Ansmant Isabelle , Hettal Liza , Rancati Tiziana , Vogin Guillaume , Thariat Juliette
Published: December 2022

(1) Background: radiotherapy is a cornerstone of cancer treatment. When delivering a tumoricidal dose, the risk of severe late toxicities is usually kept below 5% using dose-volume constraints. However, individual radiation sensitivity (iRS) is responsible (with other technical factors) for unexpected toxicities after exposure to a dose that induces no toxicity in the general population. Diagnosing iRS before radiotherapy could avoid unnecessary toxicities in patients with a grossly normal phenotype. Thus, we reviewed iRS diagnostic data and their impact on decision-making processes and the RT workflow; (2) Methods: following a description of radiation toxicities, we conducted a critical review of the current state of the knowledge on individual determinants of cellular/tissue radiation; (3) Results: tremendous advances in technology now allow minimally-invasive genomic, epigenetic and functional testing and a better understanding of iRS. Ongoing large translational studies implement various tests and enriched NTCP models designed to improve the prediction of toxicities. iRS testing could better support informed radiotherapy decisions for individuals with a normal phenotype who experience unusual toxicities. Ethics of medical decisions with an accurate prediction of personalized radiotherapy’s risk/benefits and its health economics impact are at stake; (4) Conclusions: iRS testing represents a critical unmet need to design personalized radiotherapy protocols relying on extended NTCP models integrating iRS.
Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis
Authors: Nakhjavani Maryam , Shigdar Sarah
Published: December 2022

The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood–brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. Since natural medicine has been a key inspiration for the development of the majority of current medicines, in this paper, we review several naturally-derived molecules which have the potential for immunotherapy via blocking the interaction of programmed cell death protein-1 (PD-1) and its ligand, PD-L1. The mechanism of action, physicochemical properties and pharmacokinetics of these molecules and their theoretical potential to be used for the treatment of TNBC-BM are discussed.
Impact of Mobilization Strategies on Peripheral Blood Stem Cell Collection Efficiency and Product Quality: A Retrospective Single-Center Study
Authors: Rajsp Patricija , Branka Manuela , Besson Nelly , Tanzmann Andreas , Worel Nina
Published: December 2022

Autologous stem cell transplantation is routinely used in the management of several hematological diseases, solid tumors, and immune disorders. Peripheral blood stem cell (PBSC) collection performed by apheresis is the preferred source of stem cells. In this study, the potential impact of mobilization regimens on the performance of the Spectra Optia® continuous mononuclear cell collection system was evaluated. We performed a retrospective data analysis for patients undergoing autologous PBSC collection at the Medical University Vienna, Vienna General Hospital between September 2016 and June 2018. Collections were divided into two main groups according to the mobilization regimen received: without (210 collections) or with (99 collections) plerixafor. Assessed variables included product characteristics and collection efficiency (CE). Overall, product characteristics were similar between the groups. Median CD34+ CE2 was 50.1% versus 53.0%, and CE1 was 66.9% versus 69.9% following mobilization without and with plerixafor, respectively; the difference was not statistically significant. Simple linear regression showed a very weak positive correlation between the mobilization method and CE1 or CE2 (mobilization with plerixafor increased CE2 by 4.106%). In conclusion, the Spectra Optia® apheresis system led to high CE and a good quality of PBSC products when mobilization regimens with or without plerixafor were used.
A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
Authors: Sommella Eduardo , Capaci Valeria , Aloisio Michelangelo , Salviati Emanuela , Campiglia Pietro , Molinario Giuseppe , Licastro Danilo , Di Lorenzo Giovanni , Romano Federico , Ricci Giuseppe , Monasta Lorenzo , Ura Blendi
Published: December 2022

Endometrial cancers (ECs) are mostly adenocarcinomas arising from the inner part of the uterus. The identification of serum biomarkers, either soluble or carried in the exosome, may be useful in making an early diagnosis. We used label-free quantification mass spectrometry (LFQ-MS)-based proteomics to investigate the proteome of exosomes in the albumin-depleted serum from 12 patients with EC, as compared to 12 healthy controls. After quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 33 proteins in EC vs. control samples, with a fold change of ≥1.5 or ≤0.6. Validation using Western blotting analysis in 36 patients with EC as compared to 36 healthy individuals confirmed the upregulation of APOA1, HBB, CA1, HBD, LPA, SAA4, PF4V1, and APOE. A multivariate logistic regression model based on the abundance of these proteins was able to separate the controls from the EC patients with excellent sensitivity levels, particularly for stage 1 ECs. The results show that using LFQ-MS to explore the specific proteome of serum exosomes allows for the identification of biomarkers in EC. These observations suggest that PF4V1, CA1, HBD, and APOE represent biomarkers that are able to reach the clinical stage, after a validation phase.
Influence of Butanol Isomerization on Photothermal Hydrogen Production over Ti@TiO2 Core-Shell Nanoparticles
Authors: El Hakim Sara , Bathias Mathéo , Chave Tony , Nikitenko Sergey I.
Published: December 2022

In this work, we reported for the first time the effect of butanol isomerization on the photothermal production of hydrogen in the presence of a noble, metal-free Ti@TiO2 core-shell photocatalyst. The experiments were performed in aqueous solutions of 1-BuOH, 2-BuOH, and t-BuOH under Xe lamp irradiation (vis/NIR: 8.4 W, UV: 0.6 W) at 35–69 °C. The increase in temperature significantly enhanced H2 formation, indicating a strong photothermal effect in the studied systems. However, in dark conditions, H2 emission was not observed even at elevated temperatures, which clearly points out the photonic origin of H2 photothermal formation. The rate of H2 production followed the order of 1-BuOH >> 2-BuOH > t-BuOH in the entire range of studied temperatures. In the systems with 1-BuOH and 2-BuOH, hydrogen was the only gaseous product measured online in the outlet carrier argon using mass spectrometry. By contrast, a mixture of H2, CH4, and C2H6 was detected for t-BuOH, indicating a C–C bond scission with this isomer during photocatalytic degradation. The apparent activation energies, Ea, with 1-BuOH/2-BuOH isomers (20–21 kJ·mol−1) was found to be larger than for t-BuOH (13 kJ·mol−1). The significant difference in thermal response for 1-BuOH/2-BuOH and t-BuOH isomers was ascribed to the difference in the photocatalytic mechanisms of these species. The photothermal effect with 1-BuOH/2-BuOH isomers can be explained by the thermally induced transfer of photogenerated, shallowly trapped electron holes to highly reactive free holes at the surface of TiO2 and the further hole-mediated cleavage of the O-H bond. In the system with t-BuOH, another mechanism could also contribute to the overall process through hydrogen abstraction from the C–H bond by an intermediate •OH radical, leading to CH3• group ejection. Formation of •OH radicals during light irradiation of Ti@TiO2 nanoparticle suspension in water has been confirmed using terephthalate dosimetry. This analysis also revealed a positive temperature response of •OH radical formation.
Advances in Catalytic C–F Bond Activation and Transformation of Aromatic Fluorides
Authors: Ma Rongqing , Hu Hongfan , Li Xinle , Mao Guoliang , Song Yuming , Xin Shixuan
Published: December 2022

The activation and transformation of C–F bonds in fluoro-aromatics is a highly desirable process in organic chemistry. It provides synthetic methods/protocols for the generation of organic compounds possessing single or multiple C–F bonds, and effective catalytic systems for further study of the activation mode of inert chemical bonds. Due to the high polarity of the C–F bond and it having the highest bond energy in organics, C–F activation often faces considerable academic challenges. In this mini-review, the important research achievements in the activation and transformation of aromatic C–F bond, catalyzed by transition metal and metal-free systems, are presented.
Heterojunction Design between WSe2 Nanosheets and TiO2 for Efficient Photocatalytic Hydrogen Generation
Authors: Guo Xu , Liu Xing , Shan Jing , Zhao Guangtao , Liu Shengzhong (Frank)
Published: December 2022

Design and fabrication of efficient and stable photocatalysts are critically required for practical applications of solar water splitting. Herein, a series of WSe2/TiO2 nanocomposites were constructed through a facile mechanical grinding method, and all of the nanocomposites exhibited boosted photocatalytic hydrogen evolution. It was discovered that the enhanced photocatalytic performance was attributed to the efficient electron transfer from TiO2 to WSe2 and the abundant active sites provided by WSe2 nanosheets. Moreover, the intimate heterojunction between WSe2 nanosheets and TiO2 favors the interfacial charge separation. As a result, a highest hydrogen evolution rate of 2.28 mmol/g·h, 114 times higher than pristine TiO2, was obtained when the weight ratio of WSe2/(WSe2 + TiO2) was adjusted to be 20%. The designed WSe2/TiO2 heterojunctions can be regarded as a promising photocatalysts for high-throughput hydrogen production.
Single Metal Atoms Embedded in the Surface of Pt Nanocatalysts: The Effect of Temperature and Hydrogen Pressure
Authors: Wang Qing , Zhu Beien , Tielens Frederik , Guesmi Hazar
Published: December 2022

Embedding energetically stable single metal atoms in the surface of Pt nanocatalysts exposed to varied temperature (T) and hydrogen pressure (P) could open up new possibilities in selective and dynamical engineering of alloyed Pt catalysts, particularly interesting for hydrogenation reactions. In this work, an environmental segregation energy model is developed to predict the stability and the surface composition evolution of 24 Metal M-promoted Pt surfaces (with M: Cu, Ag, Au, Ni, Pd, Co, Rh and Ir) under varied T and P. Counterintuitive to expectations, the results show that the more reactive alloy component (i.e., the one forming the strongest chemical bond with the hydrogen) is not the one that segregates to the surface. Moreover, using DFT-based Multi-Scaled Reconstruction (MSR) method and by extrapolation of M-promoted Pt nanoparticles (NPs), the shape dynamics of M-Pt are investigated under the same ranges of T and P. The results show that under low hydrogen pressure and high temperature ranges, Ag and Au—single atoms (and Cu to a less extent) are energetically stable on the surface of truncated octahedral and/or cuboctahedral shaped NPs. This indicated that coinage single-atoms might be used to tune the catalytic properties of Pt surface under hydrogen media. In contrast, bulk stability within wide range of temperature and pressure is predicted for all other M-single atoms, which might act as bulk promoters. This work provides insightful guides and understandings of M-promoted Pt NPs by predicting both the evolution of the shape and the surface compositions under reaction gas condition.
Sulfur-Resistant CeO2-Supported Pt Catalyst for Waste-to-Hydrogen: Effect of Catalyst Synthesis Method
Authors: Hong Ga-Ram , Kim Kyoung-Jin , Ahn Seon-Yong , Kim Beom-Jun , Park Ho-Ryong , Lee Yeol-Lim , Lee Sang Soo , Jeon Yukwon , Roh Hyun-Seog
Published: December 2022

To improve the sulfur tolerance of CeO2-supported Pt catalysts for water gas shift (WGS) using waste-derived synthesis gas, we investigated the effect of synthesis methods on the physicochemical properties of the catalysts. The Pt catalysts using CeO2 as a support were synthesized in various pathways (i.e., incipient wetness impregnation, sol-gel, hydrothermal, and co-precipitation methods). The prepared samples were then evaluated in the WGS reaction with 500 ppm H2S. Among the prepared catalysts, the Pt-based catalyst prepared by incipient wetness impregnation showed the highest catalytic activity and sulfur tolerance due to the standout factors such as a high oxygen-storage capacity and active metal dispersion. The active metal dispersion and oxygen-storage capacity of the catalyst showed a correlation with the catalytic performance and the sulfur tolerance.
Safety and Efficacy of Humanized Versus Murinized CD19 and CD22 CAR T-Cell Cocktail Therapy for Refractory/Relapsed B-Cell Lymphoma
Authors: Huang Lefu , Li Jingjing , Yang Junfang , Zhang Xian , Zhang Min , He Jiujiang , Zhang Gailing , Li Wenqian , Wang Hui , Li Jianqiang , Lu Peihua
Published: December 2022

CD19 chimeric antigen receptor T-cell (CAR-T) therapy is efficacious for refractory/relapsed (R/R) B-cell hematological malignancies, yet relapse due to CD19 antigen escape remains a challenge. Our trial explored simultaneous targeting of multiple B-cell antigens as a therapeutic approach that may reduce the risk of relapse. We tested the safety and efficacy of CAR19/22 T-cell cocktail therapy including murinized and humanized products among patients with R/R aggressive B-cell lymphoma. In the group that received the humanized product, 11/12 (91.7%) patients achieved an objective response, including 9/12 (75%) complete responses (CRs) by day 28. The overall response rate and CR rate in the murinized group was 92.9% (13/14) and 42.9% (6/14), respectively. Nine of 12 (75%) patients in the humanized group maintained CR at month 3 following infusion, compared to 5/14 patients (35.7%) in the murinized group. Progression-free survival (PFS) was more favorable in the humanized compared to the murinized group. Most patients had mild cytokine release syndrome (CRS) (grade 1–2) in both groups. This study demonstrates that CAR19/22 T-cell cocktail therapy is safe and effective for R/R B-cell lymphoma and that patients treated with a humanized CAR-T exhibited better efficacy compared to patients treated with a murinized CAR-T therapy.
Disruption of Multiple Overlapping Functions Following Stepwise Inactivation of the Extended Myc Network
Authors: Wang Huabo , Stevens Taylor , Lu Jie , Airik Merlin , Airik Rannar , Prochownik Edward V.
Published: December 2022

Myc, a member of the “Myc Network” of bHLH-ZIP transcription factors, supervises proliferation, metabolism, and translation. It also engages in crosstalk with the related “Mlx Network” to co-regulate overlapping genes and functions. We investigated the consequences of stepwise conditional inactivation of Myc and Mlx in primary and SV40 T-antigen-immortalized murine embryonic fibroblasts (MEFs). Myc-knockout (MycKO) and Myc × Mlx “double KO” (DKO)—but not MlxKO—primary MEFs showed rapid growth arrest and displayed features of accelerated aging and senescence. However, DKO MEFs soon resumed proliferating, indicating that durable growth arrest requires an intact Mlx network. All three KO MEF groups deregulated multiple genes and functions pertaining to aging, senescence, and DNA damage recognition/repair. Immortalized KO MEFs proliferated in Myc’s absence while demonstrating variable degrees of widespread genomic instability and sensitivity to genotoxic agents. Finally, compared to primary MycKO MEFs, DKO MEFs selectively downregulated numerous gene sets associated with the p53 and retinoblastoma (Rb) pathways and G2/M arrest. Thus, the reversal of primary MycKO MEF growth arrest by either Mlx loss or SV40 T-antigen immortalization appears to involve inactivation of the p53 and/or Rb pathways.