bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Process and Influencing Factors of Online Diabetes Information Users’ Avoidance Behavior: A Qualitative Study
Authors: Guo Caiqiang , Si Li , Sun Yifan
Published: March 2023

Users’ avoidance behavior of health information has received growing attention recently, but research into users’ avoidance behavior of diabetes information remains limited. This paper aims to reveal the process and the factors of avoiding online diabetes information. The interview, conducted with the critical incident technique, and the diary methods were used to collect 40 true incidents of online diabetes information avoidance from 17 participants. Based on the thematic analysis method and grounded theory, the data were analyzed to identify the key phases of the avoidance process and obtain the factors influencing the occurrence of avoidance behavior. The results showed that the macro-process of online diabetes information avoidance comprised three phases: pre-encountering, encountering, and avoiding after encountering. First, browsing, searching, or social interaction provide the context for encountering; second, the encountering occurrence consists of three steps—noticing the stimuli, reacting to stimuli, and examining the content; and third, to avoid the online diabetes information encountered, users will adopt avoidance strategies, such as avoiding information sources, controlling attention, delaying access, forgetting information, and denying information, which is manifested as general avoidance and strong avoidance, and has positive, negative, or no effect on users. The 14 influencing factors of avoidance behavior obtained were divided into four clusters. User-related factors include demographic characteristics, health-behavior perception, perceived threat, perceived control, and information sufficiency; information-related factors include information quality, information overload, and information dissemination; environment-related factors include context type, behavior place, time pressure, and social factors, and emotion-related factors include the pre-encountering and post-encountering emotional states. These findings can guide the intervention of information avoidance behavior.
Pain Perceptions, Suffering and Pain Behaviours of Professional and Pre-Professional Dancers towards Pain and Injury: A Qualitative Review
Authors: Soundy Andrew , Lim Ja Yee
Published: March 2023

Limited data exist that describe the experiences of pain and injury in dancers. The purpose of the current study was to understand pain perceptions, suffering and pain behaviours associated with pre-professional and professional dancers and to consider the psychosocial factors that influence suffering, behaviour and perceptions of pain. A thematic synthesis review was undertaken in three stages: (1) A systematic search using pre-defined search terms was conducted until 17 November 2022. Qualitative studies were included if they captured dancers’ perceptions, experiences, or the behaviour of dancers towards pain and injury. (2) Quality appraisal and certainty assessments was performed. (3) A five-phase synthesis generated themes that included a certainty assessment score. Twelve studies with 290 dancers met the inclusion criteria. The aggregated mean age was identified as 28.5 years. No studies were excluded following the quality appraisal stage. Nine studies included professional ballet dancers. Three themes were developed: (1) developing positive and adapted perceptions and behaviours towards pain, (2) the impact and danger of embracing pain and the risk of injury and (3) factors that influenced the response to injury and the ability to perform. This review has highlighted the experiences of pre-professional and professional dancers towards pain and injury. Practical implications for healthcare professionals, employers, choreographers and dancers are provided. Further research is required given the limited evidence base.
The Effect of Perfectionism on Consumers’ Intentions to Purchase Imperfect Products
Authors: Chen Libin , Chen Guanhong , Wang Shuo , Jiang Lin
Published: March 2023

Perfectionism is an important personality trait that affects people’s behavior, especially consumption behavior. In our study, we aimed to investigate whether perfectionists show different preferences in their consumption choices compared with non-perfectionists and to explore the potential psychological mechanisms mediating this effect. Through four studies, we found that perfectionists are less likely to buy imperfect products, including those that are close to expiry and that have defective functioning, flawed appearance, and incomplete after-sales service than non-perfectionists, and are more likely to avoid choosing imperfect products. In addition, we found a mediating effect of dichotomous thinking and intolerance of uncertainty on this effect to explain the behavioral preferences of perfectionists in their purchasing choices. Manufacturers and marketers can benefit from the results of this study by implementing targeted production requirements and marketing strategies based on the consumer behavior preferences of perfectionists.
Understanding Different Types of Followers’ Engagement and the Transformation of Millennial Followers into Cosmetic Brand Evangelists
Authors: Rungruangjit Warinrampai , Chankoson Thitinan , Charoenpornpanichkul Kitti
Published: March 2023

Facebook pages of cosmetic products have substantially grown among millennial consumers. This study aims to explore the motivational factors that affect different types of millennial followers’ engagement, including followers on Facebook pages of cosmetic products, and examine different types of millennial followers’ engagement that influence brand evangelism. A quantitative method involving the technique of partial least square structural equation modeling was applied. An online questionnaire was designed to collect data from millennial followers. The results revealed that informational content stimulates active lurkers and passive participants, while entertaining content positively influences only active participants. Social interaction value is influential to active and passive participants. It was found that identification is the motivation factor that drives both active participants and lurkers. Confidence benefits and special treatment benefits were found to be the motivation factor that stimulates all participants. Social benefits substantially influence active participants and lurkers. Interestingly, the followers’ passive participation has a great influence on brand evangelism. This study opposes the notion that active lurkers and passive participants are less important than active participants and supports the literature by revealing the importance of distinguishing between active participants, active lurkers, and passive participants in causing different impacts on brand evangelism.
Highway to the Comfort Zone: History of the Psychrometric Chart
Authors: Teitelbaum Eric , Miller Clayton , Meggers Forrest
Published: March 2023

The psychrometric chart is the most common data visualization technique for the designers of thermal comfort systems worldwide. From its humble roots as means of expressing the characteristics of air in building systems design, the use of the chart has grown to include the representation of the zones of human thermal comfort according to both conventional and adaptive models. In this paper, we present an extensive history of this development and the fallacies with representing comfort simply as a box that sometimes moves on the chart. The origins of the link between refrigeration control and comfort control are examined through archival reviews, examining the works of Carrier, Yagoglou, and their contemporaries in the context of modern comfort mischaracterizations. A clearer understanding of the mapping of comfort, control, and climate metrics with psychrometrics is reported, and a critique of the conflation is reported to increase awareness of the limitations of such treatment of these three critical domains.
Numerical Simulation of the Dynamic Responses and Impact-Bearing Capacity of CFDST Columns under Lateral Impact
Authors: Guo Jin-Long , Pan Shuang , Guo Xiao , Wu Zheng-Yu
Published: March 2023

The concrete-filled double steel tube (CFDST) has been more and more widely used in infrastructure due to its greater moment of inertia compared to the ordinary concrete-filled steel tube (CFST). With the increase in collision accidents occurring in recent years, the research on CFDST under impact needs more attention. To study the dynamic responses of CFDST columns under lateral impact, the finite element package ABAQUS was used to simulate the impact force and mid-span deflection of the column under the coupling action of axial force and lateral impact based on the comparison of experimental data in the literature. The influence of hollow ratio, axial compression ratio, slenderness ratio, impact energy, and material strength on the dynamic responses of the CFDST column are studied. The results show that with the increase in the hollow ratio from 0.3 to 0.8, the residual mid-span deflection of the CFDST column decreases by 77.9%. The mid-span deflection shows an increasing trend following a decreasing one with the axial compression ratio increasing. With the increase in the slenderness ratio from 30 to 60, the plateau impact force decreases by 62.5%, and the residual mid-span deflection increases by 240.5%. The practical formulas for the impact-bearing capacity and residual mid-span deflection of the CFDST column are suggested with high accuracy.
Mechanism and Design Method of Load Transfer into Concrete-Filled Steel Tubular Arch Ribs through Perfobond-Rib-Shear Connectors
Authors: Liu Yongjian , Li Jiangjiang , Jiang Lei , Xian Jianping , Li Haotian , Zhao Yadong , Gong Yunxia
Published: March 2023

In terms of load transfer, the design of the joints in concrete-filled steel tubular (CFST) arch bridges is more critical than that in buildings due to the higher likelihood of steel–concrete-interface debonding. To improve the contact at the steel–concrete interface, a novel arch rib was manufactured by longitudinally welding perfobond-rib-shear connectors to the inner surface of a steel tube and then filling the tube with concrete. In this study, extensive numerical and analytical investigations on the mechanism of introducing loads into CFST arch ribs through perfobond-rib-shear connectors were carried out. A deck CFST arch bridge, namely, the Shuangbao Bridge in China, was selected as a typical application location. The design parameters, including the geometric dimensions of the perfobond-rib-shear connector and the arrangement of the perfobond rib along the cross-section and longitudinal section of the arch rib, were evaluated. The design flow for the joint with perfobond-rib-shear connectors between the vertical columns and the CFST arch ribs was proposed. To improve the load-transfer efficiency, the design scheme of the joint in the Shuangbao Bridge was optimized by replacing the weld studs with perfobond ribs. Significant increases of 1.84–4.02 in the shear resistance were found for the perfobond ribs compared to the welded studs. Additionally, the fabrication of the perfobond ribs was more convenient compared to that of the welded studs.
Influence of Tunnel Excavation on the Deformation of a Frame Building
Authors: Li Yang , Zhou Guangyi , Li Tianjiao , Tang Chun’an , Gong Bin , Wang Kaikai
Published: March 2023

Tunnel excavation inevitably causes surface deformation. In urban areas, surface deformation could lead to the deformation of surrounding buildings, which may cause damage to communities when accumulated to a certain extent. However, the current construction organization and management mainly rely on on-site deformation measurements, and there is still a lack of reliable prediction methods. Here, we proposed an effective evaluation method for frame building deformation based on the stochastic medium theory and the equivalent beam theory. This method could effectively evaluate the surface and building deformation after a horseshoe tunnel excavation by considering the non-uniform convergence. Furthermore, its accuracy and practicability were verified using the Nanyan Fourth Circuit Transmission Reconstruction located in Dalian, China. The results show that the spatial distribution and characteristic values of the maximum tensile strains were closely related to the ratio of Young’s modulus to the shear modulus (E/G), the building height (h), the tunnel depth (H), the tangent of the tunnel influence angle (tan β) and the convergence radius (ΔR). These achievements can provide a theoretical basis and analytical ideas for investigating the influence of shallow buried tunnel excavation on frame structure buildings in cities.
Defect Repair Deposit and Insurance Premium for a New Home Warranty in Korea
Authors: Park Junmo , Seo Deokseok
Published: March 2023

Disputes due to defects in newly built houses are increasing worldwide. A house builder is responsible for repairing any defects in a newly built house. However, since house builders’ risk of closure and bankruptcy are increasing due to aggravated disputes and economic crises, builders may become insolvent and fail to perform defect repairs. In preparation for this, many countries have established defect repair deposit or guaranty insurance systems; however, the standards for these systems are not based an objective evidence since the current standards were arbitrarily established during industrialization. It has been pointed out that Korea’s housing defect repair deposit has been set excessively high and is being abused in disputes. Based on dispute cases in Korea, this study analyzed housing construction costs, deposits, and defect repair costs, resulting from lawsuits due to defects. The results confirmed that the defect repair deposit has been set too high compared to incurred defect repair costs. In addition, it was found that the guaranty insurance premium in lieu of the housing defect repair deposit was excessive compared to the damage caused by builder insolvency. In order to improve this, in this study, we proposed two alternative plans in which the housing defect repair deposit was set at a certain percentage of the construction cost based on the current Korean standard. In addition, based on the concept of different deposit levels using the scale of housing construction, such as in Australia and Canada, two additional alternative plans with different deposit ratios for each scale of housing construction were presented. The comparison results for housing defect repair deposits and guaranty insurance premiums based on the four presented alternative plans accompanied by actual cases showed that all the alternative plan deposits were higher than the actual defect repair costs. Even in the case of a guaranty insurance premium, the level was at least twice as high as the damage caused by builder insolvency. Therefore, all the alternative plans can fulfill their original role of protecting homeowners in the case of builder insolvency. At the same time, reducing the guaranty insurance premium to reflect the cost of housing construction is possible, and would benefit both house builders and home buyers. The results of this study are valuable as a reference for other countries considering establishing or revising a housing defect repair deposit system. Specifically, these findings, which analyzed the case of Korea’s socioeconomic changes as it transitioned from a developing country to a developed country, can provide important information for many developing countries operating housing defect repair deposit policies and systems.
Experimental Study on the Influence of Humidity on Double-K Fracture Toughness and Fracture Energy of Concrete under Water Environment
Authors: Zhang Guohui , Ni Xinlan , Wei Xiong , Yang Zhendong , Gu Yanshuang
Published: March 2023

Saturated concrete is significantly different from dry concrete in fracture mechanical properties. Using the wedge-splitting tensile method to research the rule of change in moisture content, double-K fracture toughness and fracture energy of three strength grades (C20, C30, and C40) of concrete immersed in a free water environment for 0 h, 2 h, 5 h, 24 h, and 120 h were studied in order to provide support for the safety evaluation of concrete structures in a water environment. The initial cracking fracture toughness of C20, C30, and C40 concrete in saturated state were, respectively, 29.6%, 23.2%, and 33.4% lower than that in dry state. The unstable fracture toughness of C20, C30, and C40 concrete in saturated state were, respectively, 22.7%, 23.9% and 33.8% lower than that in dry state. The fracture energy of C20, C30, and C40 concrete in saturated state are only 71.99%, 70.29%, and 66.11% of that in dry state, respectively. The initial cracking fracture toughness and unstable fracture toughness of concrete all show a linear, decreasing trend with an increase in moisture content. Before the crack initiation, the measured P–CMOD curve had an obvious linear elastic stage, stable expansion stage, and unstable expansion stage. The critical crack opening displacement gradually decreases with an increase in moisture content; the deformation capacity and toughness of concrete are shown to decrease. The humidity state should be fully considered when evaluating the fracture mechanical properties of concrete.
Inhibitors of the Oncogenic PA2G4-MYCN Protein-Protein Interface
Authors: Massudi Hassina , Luo Jie-Si , Holien Jessica K. , Gadde Satyanarayana , Krishan Sukriti , Herath Mika , Koach Jessica , Stevenson Brendan W. , Gorman Michael A. , Venkat Pooja , Mayoh Chelsea , Luo Xue-Qun , Parker Michael W. , Cheung Belamy B. , Marshall Glenn M.
Published: March 2023

MYCN is a major oncogenic driver for neuroblastoma tumorigenesis, yet there are no direct MYCN inhibitors. We have previously identified PA2G4 as a direct protein-binding partner of MYCN and drive neuroblastoma tumorigenesis. A small molecule known to bind PA2G4, WS6, significantly decreased tumorigenicity in TH-MYCN neuroblastoma mice, along with the inhibition of PA2G4 and MYCN interactions. Here, we identified a number of novel WS6 analogues, with 80% structural similarity, and used surface plasmon resonance assays to determine their binding affinity. Analogues #5333 and #5338 showed direct binding towards human recombinant PA2G4. Importantly, #5333 and #5338 demonstrated a 70-fold lower toxicity for normal human myofibroblasts compared to WS6. Structure-activity relationship analysis showed that a 2,3 dimethylphenol was the most suitable substituent at the R1 position. Replacing the trifluoromethyl group on the phenyl ring at the R2 position, with a bromine or hydrogen atom, increased the difference between efficacy against neuroblastoma cells and normal myofibroblast toxicity. The WS6 analogues inhibited neuroblastoma cell phenotype in vitro, in part through effects on apoptosis, while their anti-cancer effects required both PA2G4 and MYCN expression. Collectively, chemical inhibition of PA2G4-MYCN binding by WS6 analogues represents a first-in-class drug discovery which may have implications for other MYCN-driven cancers.
Recent Progress in the Diagnosis and Treatment of Melanoma and Other Skin Cancers
Authors: Pawlik Laura , Morgenroth Sarah , Dummer Reinhard
Published: March 2023

In this Special Issue, the reader will find nine papers regarding recent progress in diagnosis and treatment to optimize the clinical management of melanoma and non-melanoma skin cancer [...]
Associations of T-Cell Receptor Repertoire Diversity with L-Asparaginase Allergy in Childhood Acute Lymphoblastic Leukemia
Authors: Lee Shawn H. R. , Li Zhenhua , Lim Evelyn H. Z. , Chin Winnie H. N. , Jiang Nan , Chiew Kean Hui , Chen Zhiwei , Oh Bernice L. Z. , Tan Ah Moy , Ariffin Hany , Yang Jun J. , Yeoh Allen E. J.
Published: March 2023

Asparaginase is a critical component of therapy for childhood acute lymphoblastic leukemia (ALL), but it is commonly associated with allergy, which results in morbidity and poorer outcomes. The underlying basis of this allergy is undoubtedly immune-mediated, but the exact components of T-cell immunity have yet to be characterized. We performed longitudinal TCR sequencing of 180 bone marrow samples from 67 children with B-ALL treated as part of the Ma-Spore-ALL-2010 trial, and we evaluated the associations of TCR profile with asparaginase hypersensitivity, with functional validation of asparaginase activity in a separate cohort of 113 children. We found that a more diverse and dynamically changing TCR repertoire was associated with increased risk of clinical hypersensitivity and decreased L-asp activity. Allergic patients had a higher proportion of infrequent clonotypes, as well as a significantly lower degree of shared clonotypes amongst the cohort. Allergic patients also had significantly higher longitudinal variability of clonotypes across timepoints, where a higher dissimilarity between diagnosis and week 5 represented an 8.1-fold increased risk of an allergic event. After an allergy had occurred, there was shaping and convergence of the TCR repertoire towards a common antigen. Understanding the immunological basis of T-cell responses in allergy lays the groundwork for developing predictive biomarkers or strategies to mediate this common toxicity in childhood ALL.
Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways and COP1 in Metastasis
Authors: Xiao Jerry , Sharma Utsav , Arab Abolfazl , Miglani Sohit , Bhalla Sonakshi , Suguru Shravanthy , Suter Robert , Mukherji Reetu , Lippman Marc E. , Pohlmann Paula R. , Zeck Jay C. , Marshall John L. , Weinberg Benjamin A. , He Aiwu Ruth , Noel Marcus S. , Schlegel Richard , Goodarzi Hani , Agarwal Seema
Published: March 2023

Circulating tumor cells (CTCs), a population of cancer cells that represent the seeds of metastatic nodules, are a promising model system for studying metastasis. However, the expansion of patient-derived CTCs ex vivo is challenging and dependent on the collection of high numbers of CTCs, which are ultra-rare. Here we report the development of a combined CTC and cultured CTC-derived xenograft (CDX) platform for expanding and studying patient-derived CTCs from metastatic colon, lung, and pancreatic cancers. The propagated CTCs yielded a highly aggressive population of cells that could be used to routinely and robustly establish primary tumors and metastatic lesions in CDXs. Differential gene analysis of the resultant CTC models emphasized a role for NF-κB, EMT, and TGFβ signaling as pan-cancer signaling pathways involved in metastasis. Furthermore, metastatic CTCs were identified through a prospective five-gene signature (BCAR1, COL1A1, IGSF3, RRAD, and TFPI2). Whole-exome sequencing of CDX models and metastases further identified mutations in constitutive photomorphogenesis protein 1 (COP1) as a potential driver of metastasis. These findings illustrate the utility of the combined patient-derived CTC model and provide a glimpse of the promise of CTCs in identifying drivers of cancer metastasis.
Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)—A Prospective Multicentric Cohort Study
Authors: Kämmerer Peer W. , Tribius Silke , Cohrs Lena , Engler Gabriel , Ettl Tobias , Freier Kolja , Frerich Bernhard , Ghanaati Shahram , Gosau Martin , Haim Dominik , Hartmann Stefan , Heiland Max , Herbst Manuel , Hoefert Sebastian , Hoffmann Jürgen , Hölzle Frank , Howaldt Hans-Peter , Kreutzer Kilian , Leonhardt Henry , Lutz Rainer , Moergel Maximilian , Modabber Ali , Neff Andreas , Pietzka Sebastian , Rau Andrea , Reichert Torsten E. , Smeets Ralf , Sproll Christoph , Steller Daniel , Wiltfang Jörg , Wolff Klaus-Dietrich , Kronfeld Kai , Al-Nawas Bilal
Published: March 2023

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55–1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15–0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19–0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.
Inflammation, Infiltration, and Evasion—Tumor Promotion in the Aging Breast
Authors: Cruz-Reyes Nicole , Radisky Derek C.
Published: March 2023

Breast cancer is a significant cause of morbidity and mortality in women, with over two million new cases reported worldwide each year, the majority of which occur in post-menopausal women. Despite advances in early detection and treatment, approximately one-third of patients diagnosed with breast cancer will develop metastatic disease. The pathogenesis and progression of breast cancer are influenced by a variety of biological and social risk factors, including age, ethnicity, pregnancy status, diet, and genomic alterations. Recent advancements in breast cancer research have focused on harnessing the power of the patient’s adaptive and innate immune systems for diagnostic and therapeutic purposes. The breast immune microenvironment plays a critical role in regulating tissue homeostasis and resistance to tumorigenesis. In this review, we explore the dynamic changes in the breast immune microenvironment that occur with age, how these changes impact breast cancer development and progression, and how targeted therapeutic interventions that leverage the immune system can be used to improve patient outcomes. Our review emphasizes the importance of understanding the complex interplay between aging, the immune system, and breast cancer, and highlights the potential of immune-based therapies in the fight against this devastating disease.
Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis
Authors: Lee Jerry C. , Logan Aaron C.
Published: March 2023

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe, dysregulated inflammation driven by the inability of T cells to clear an antigenic target. When associated with malignancy (mHLH), the HLH syndrome is typically associated with extremely poor survival. Here, we review the diagnosis of secondary HLH (sHLH) syndromes in adults, with emphasis on the appropriate workup and treatment of mHLH. At present, the management of HLH in adults, including most forms of mHLH, is based on the use of corticosteroids and etoposide following the HLH-94 regimen. In some cases, this therapeutic approach may be cohesively incorporated into malignancy-directed therapy, while in other cases, the decision about whether to treat HLH prior to initiating other therapies may be more complicated. Recent studies exploring the efficacy of other agents in HLH, in particular ruxolitinib, offer hope for better outcomes in the management of mHLH. Considerations for the management of lymphoma-associated mHLH, as well as other forms of mHLH and immunotherapy treatment-related HLH, are discussed.
Tumour Necrosis Factor Alpha (TNF-α) and Oral Squamous Cell Carcinoma
Authors: Brierly Gary , Celentano Antonio , Breik Omar , Moslemivayeghan Elham , Patini Romeo , McCullough Michael , Yap Tami
Published: March 2023

Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment.
Advances in PARP Inhibitors for Prostate Cancer
Authors: Tisseverasinghe Steven , Bahoric Boris , Anidjar Maurice , Probst Stephan , Niazi Tamim
Published: March 2023

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.
Systemic Inflammation and Lung Cancer: Is It a Real Paradigm? Prognostic Value of Inflammatory Indexes in Patients with Resected Non-Small-Cell Lung Cancer
Authors: Mazzella Antonio , Maiolino Elena , Maisonneuve Patrick , Loi Mauro , Alifano Marco
Published: March 2023

Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, who were referred to our department between 1 January 2017 and 30 December 2018. The inflammatory pre-operative status of the patients was investigated by calculating albumin, CPR (c-protein reactive), complete blood count (neutrophils, lymphocytes, platelets, hemoglobin), and some other indexes referring to inflammatory status, namely the HALP amalgamated index, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes ratio (NLR), systemic immune-inflammation index (SII), and advanced lung cancer inflammation Index (ALI). The follow-up ended in November 2021. Patient overall survival was assessed using the Kaplan–Meier method. The log-rank test was used to compare survival rates. Variables significantly associated with survival at univariate analysis were entered int Cox multivariate analysis (stepwise mode) to assess their independent character. Hazard ratios and their 95% confidence intervals were calculated. Variables associated with p < 0.05 were considered significative. Results (3): We enrolled 257 patients in our study. The overall survival of the cohort was as follows: 1 year, 96.1%; 3 year, 81.3%; and 4 year, 74.2%. Univariate analysis showed risk factors for overall survival as follows: Thoracoscore ≥ 2 (p = 0.002); histology (p = 0.002); HALP < 32.2 (p = 0.0002); SII ≥ 808.9 (p = 0.0004); ALI < 34.86 (p = 0.0005); NLr ≥ 2.29 (p = 0.01); hemoglobin < 13 g/dl (p = 0.01); PLR ≥ 196.1 (p = 0.005); pN+ (p < 0.0001); pleural invasion (p = 0.0002); and presence of vascular or lymphatic tumor emboli (p = 0.0002). Multivariate Cox analysis (stepwise model) identified Thoracoscore ≥ 2 (p = 0.02); histology, HALP < 32.2 (p = 0.004), and pN (p < 0.0001) as independent predictors of death. Conclusion (4): Pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery.
New Approaches to Targeting Epigenetic Regulation in Bladder Cancer
Authors: Thompson Daryl , Lawrentschuk Nathan , Bolton Damien
Published: March 2023

Epigenetics is a growing field and in bladder cancer, it is of particular interest in advanced or metastatic disease. As opposed to genetic mutations in which the nucleotide sequence itself is altered, epigenetic alterations refer to changes to the genome that do not involve nucleotides. This is of great interest in cancer research because epigenetic alterations are reversible, making them a promising target for pharmacological agents. While chemoimmunotherapy is the mainstay for metastatic disease, there are few alternatives for patients who have progressed on first- or second-line treatment. By targeting reversible epigenetic alterations, novel epigenetic therapies are important potential treatment options for these patients. A search of clinical registries was performed in order to identify and collate epigenetic therapies currently in human trials. A literature search was also performed to identify therapies that are currently in preclinical stages, whether this be in vivo or in vitro models. Twenty-five clinical trials were identified that investigated the use of epigenetic inhibitors in patients with bladder cancer, often in combination with another agent, such as platinum-based chemotherapy or pembrolizumab. The main classes of epigenetic inhibitors studied include DNA-methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and histone methyltransferase (HMT) inhibitors. At present, no phase 3 clinical trials have been registered. Few trials have published results, though DNMT inhibitors have shown the most promise thus far. Many patients with advanced or metastatic bladder cancer have limited treatment options, particularly when first- or second-line chemoimmunotherapy fails. Epigenetic alterations, which are common in bladder cancer, are potential targets for drug therapies, and these epigenetic agents are already in use for many cancers. While they have shown promise in pre-clinical trials for bladder cancer, more research is needed to assess their benefit in clinical settings.
Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era
Authors: Briski Robert , Taylor Justin
Published: March 2023

Richter Transformation (RT) refers to the development of an aggressive lymphoma in the setting of chronic lymphocytic leukemia (CLL). While many variants of RT are recognized, diffuse large B-cell lymphoma (RT-DLBCL) is the most common (80%), followed by Hodgkin’s lymphoma (RT-HL, 19%). Diagnosis is based upon histologic evaluation of clinically suspicious lymph nodes. Positron emission tomography (PET) may be used to select the node of interest for biopsy. Although clonality testing is not a prerequisite of RT diagnosis, it has significant implications for survival. Clonally related DLBCL carries the worst prognosis with a median overall survival (OS) of less than one year in the era of combination chemotherapies with or without anti-CD20 antibodies. Prognosis has improved with the use of stem cell transplant and newer agents such as targeted therapy and newer forms of immunotherapy. Consideration of a clinical trial is encouraged. This review describes our current understanding of RT and focuses on treatment of RT-DLBCL, including clinical trials in progress and new therapies in development. We also report an illustrative example of a patient with clonally related DLBCL who survived two years after diagnosis without the use of combination chemotherapy.
Abbreviated MRI for Comprehensive Regional Lymph Node Staging during Pre-Operative Breast MRI
Authors: Bode Maike , Schrading Simone , Masoumi Arghavan , Morscheid Stephanie , Schacht Sabine , Dirrichs Timm , Gaisa Nadine , Stickeler Elmar , Kuhl Christiane K.
Published: March 2023

Background: The detection of regional lymph node metastases (LNM), in particular significant LNM (≥N2), is important to guide treatment decisions in women with breast cancer. The purpose of this study was to determine whether a coronal pulse sequence as part of pre-operative breast MRI is useful to identify women without significant LNM. Material: Retrospective study between January 2017 and December 2019 on 414 consecutive women with breast cancer who underwent pre-operative breast MRI on a 1.5 T system. For lymph node (LN) staging, a coronal pre-contrast non-fat-suppressed T1-weighted TSE sequence was acquired with the system’s built-in body coil, covering the chest wall; acquisition time 3:12 min. Two radiologists rated the likelihood of LNM on a 3-point scale (absent/possible/present). Validation was obtained by histology from sentinel LN biopsy, axillary LN dissection, and/or PET/CT. Results: 368/414 women were staged to have no or non-significant LNM (pN0 in 282/414, pN1 in 86/414), and significant LNM (≥pN2) in 46/414. For identification of women with significant LNM, MRI was true-positive in 42/46, false-negative in 4/46, true-negative in 327/368, and false-positive in 41/83, the latter mostly caused by women with N1-disease (38/41), yielding an NPV and PPV for significant LNM of 98.8% [95%-CI: 97.0–100%] and 50.6% [43.1–58.1%], respectively. Conclusions: A 3 min coronal T1-weighted pulse sequence covering the chest wall as part of pre-operative breast MRI is useful to rule out significant LNM with high NPV. Where MRI staging is positive for significant LNM, additional work-up is indicated to improve the distinction of N1 and N2 disease.
Detection of Cellular Senescence Reveals the Existence of Senescent Tumor Cells within Invasive Breast Carcinomas and Related Metastases
Authors: Cotarelo Cristina L. , Schad Arno , Schmidt Marcus , Hönig Arnd , Sleeman Jonathan P. , Thaler Sonja
Published: March 2023

Oncogene-induced senescence is thought to constitute a barrier to carcinogenesis by arresting cells at risk of malignant transformation. However, numerous findings suggest that senescent cells may conversely promote tumor growth and metastatic progression, for example, through the senescence-associated secretory phenotype (SASP) they produce. Here, we investigated the degree to which senescent tumor cells exist within untreated human primary breast carcinomas and whether the presence of senescent cancer cells in primary tumors is recapitulated in their matched lymph node metastases. For the detection of senescence, we used SA-β-galactosidase (SA-β-gal) staining and other senescence markers such as Ki67, p21, p53, and p16. In patients with invasive luminal A and B breast carcinomas, we found broad similarities in the appearance of cancer cells between primary tumors and their corresponding metastases. Analysis of lymph nodes from patients with other breast cancer subtypes also revealed senescent tumor cells within metastatic lesions. Collectively, our findings show that senescent tumor cells exist within primary breast carcinomas and metastatic lesions. These results suggest a potential role for senescent breast tumor cells during metastatic progression and raise the question as to whether the targeting of senescent tumor cells with anti-senescent drugs might represent a novel avenue for improved treatment of breast and other cancers.
Influence of Sodium Metal Nanoparticles on the Efficiency of Heavy Oil Aquathermolysis
Authors: Katnov Vladimir E. , Trubitsina Sofya A. , Kayumov Aydar A. , Aliev Firdavs A. , Nazimov Nafis A. , Dengaev Aleksey V. , Vakhin Alexey V.
Published: March 2023

In this study, for the first time we investigated the in situ upgrading performance of Na metal nanoparticles, which were obtained by dispersing small pieces of sodium in liquid paraffin up to certain dispersity. In situ aquathermolytic reactions were modeled in a high pressure–high temperature reactor coupled with a Gas Chromatography (GC) system at a temperature of 250 °C for 24 h using a heavy oil sample, produced from the Ashal’cha reservoir, Republic of Tatarstan (Russia). The mean particle size of Na nanoparticles was 6.5 nm determined by the Dynamic Light Scattering (DLS) method. The nanoparticles were introduced to the reaction medium with a concentration of 2 wt.% The upgrading performance of Na nanoparticles was evaluated by several analytical methods such as Gas Chromatography (GC), elemental analysis (CHNS), SARA, Gas Chromatography–Mass Spectroscopy (GC-MS), FT-IR spectroscopy and viscosity measurements. It was revealed that Na nanoparticles interact with water to yield hydrogen gas, the concentration of which increases from 0.015 to 0.805 wt.% Moreover, the viscosity of upgraded heavy oil was reduced by more than 50% and the content of low-molecular-weight hydrocarbons in saturated and aromatics fractions was increased. The Na nanoparticles contributed to the utilization of hydrogen sulfide and carbon dioxide by 99 and 94 wt.%, respectively.
Manganese-Based Metal-Organic Frameworks Photocatalysts for Visible Light-Driven Oxidative Coupling of Benzylamine under Atmospheric Oxygen: A Comparative Study
Authors: Siddig Lamia A. , Alzard Reem H. , Abdelhamid Abdalla S. , Alzamly Ahmed
Published: March 2023

Research on the utilization of sustainable and renewable energy sources has increased as a result of the world’s expanding energy demand. In this regard, we report the photocatalytic performance of two synthesized Mn-MOFs: MnII3(tp)6/2(bpy)2.(dmf) (C47H35Mn3N5O13) and Mn2(tpa)2(dmf)2 (C22H22Mn2N2O10). The two MOFs were characterized using different spectroscopic and analytical techniques: powder X-ray diffraction, thermogravimetric analysis, diffuse reflectance spectroscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. MnII3(tp)6/2(bpy)2.(dmf) possesses a band gap value of 2.5 eV, which exhibits significant photocatalytic activity when exposed to simulated visible light irradiation. Mn2(tpa)2(dmf)2 shows a larger band gap of 3.16 eV, which renders the photocatalytic performance under visible light. The oxidation of benzylamine to N,N-benzylidenebenzylamine by a photocatalytic reaction was selected to evaluate the photocatalytic activities of MnII3(tp)6/2(bpy)2.(dmf) and Mn2(tpa)2(dmf)2 in the visible region. In addition to its high photocatalytic performance, MnII3(tp)6/2(bpy)2.(dmf) also showed high thermal stability up to 430 °C. Accordingly, the strategy of designing frameworks possessing mixed ligands provides stability to the frameworks as well as enhancing the photocatalytic performance of frameworks containing bipyridine ligands such as MnII3(tp)6/2(bpy)2.(dmf).
Influence of HB2Nb3O10-Based Nanosheet Photocatalysts (B = Ca, Sr) Preparation Method on Hydrogen Production Efficiency
Authors: Kurnosenko Sergei A. , Voytovich Vladimir V. , Silyukov Oleg I. , Rodionov Ivan A. , Malygina Ekaterina N. , Zvereva Irina A.
Published: March 2023

Photocatalytic activity of HB2Nb3O10 perovskite nanosheets (B = Ca, Sr) has been systematically investigated in the reactions of hydrogen production, depending on the method of the photocatalyst preparation: using the pristine nanosheets in the parent suspension without reassembly, filtered nanosheets as well as nanosheets restacked by hydrochloric acid. Photocatalytic measurements were organized in such a way as to control a wide range of parameters, including the hydrogen generation rate, quantum efficiency of the reaction, potential dark activity of the sample as well as stability and pH of the reaction suspension. Exfoliation of the niobates into nanosheets allowed obtaining efficient photocatalysts surpassing the initial bulk materials in the activity up to 55 times and providing apparent quantum efficiency up to 20.8% after surface decoration with a Pt cocatalyst. Among the reassembled samples, greater hydrogen evolution activity was exhibited by simply filtered nanosheets that, unlike the HCl-restacked ones, were found to possess much lower specific surface area in a dry state but contain a perceptible amount of tetrabutylammonium cations on the surface. The activity difference, potentially, is associated with the fact that the filtered nanosheets undergo ultrasonic disaggregation before photocatalytic tests much easier than their HCl-restacked counterparts and, thanks to this, have greater active surface in the reaction suspension. In addition, the enhanced activity of the filtered nanosheets may be due to the presence of tetrabutylammonium as an organic modifier on their surface, which is consistent with the high photocatalytic performance of organically modified layered perovskites considered in our previous reports.
Effect of Urea as a Shape-Controlling Agent on the Properties of Bismuth Oxybromides
Authors: Márta Viktória , Pap Zsolt , Bárdos Enikő , Gyulavári Tamás , Veréb Gábor , Hernadi Klara
Published: March 2023

Bismuth oxybromides were prepared via a solvothermal method by applying different urea amounts during synthesis. The effects of the urea ratio on the morpho–structural properties and photocatalytic activity of the samples were investigated. X-ray diffraction, diffuse reflectance spectroscopy, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and surface tension measurements were carried out to characterize the samples. Their photoactivity was evaluated by the photocatalytic degradation of rhodamine B and ibuprofen under UV and visible light irradiations. The urea ratio notably influenced morphology, particle size distribution, and photoactivity. However, it only had a limited effect on the crystalline composition, primary crystallite size, and band gap of bismuth oxybromides. The formation of Bi-based complexes and degraded urea-based products were observed, which were deduced to influence band gap energies and hence, photoactivity. Predominantly, samples prepared at low urea ratios proved to be the best for both rhodamine B and ibuprofen degradations under both irradiations.