bluuebunny/crossref_metadata_2025 huggingface dataset:
High Specific and Rapid Detection of Cannabidiol by Gold Nanoparticle-Based Paper Sensor
Authors: Sun Yufeng , Zhu Dong , Tao Ran , Li Long , Fan Bei , Wang Fengzhong
Published: October 2023

In order to facilitate monitoring of cannabidiol (CBD), we devised a gold immunochromatographic sensor based on a specific monoclonal antibody (mAb). To prepare the antigen, a novel hapten with CBD moiety and a linear carbon chain was employed. By utilizing hybridoma technology, a specific mAb was screened and identified that exhibited a 50% maximal inhibitory concentration against CBD ranging from 28.97 to 443.97 ng/mL. Extensive optimization led to the establishment of visual limits of detection for CBD, achieving a remarkable sensitivity of 8 μg/mL in the assay buffer. To showcase the accuracy and stability, an analysis of CBD-spiked wine, sparkling water, and sports drink was conducted. The recovery rates observed were as follows: 88.4–109.2% for wine, 89.9–107.8% for sparkling water, and 83.2–95.5% for sports drink. Furthermore, the coefficient of variation remained impressively low, less than 4.38% for wine, less than 2.07% for sparkling water, and less than 6.34% for sports drink. Importantly, the developed sensor exhibited no cross-reaction with tetrahydrocannabinol (THC). In conclusion, the proposed paper sensor, employing gold nanoparticles, offers a user-friendly and efficient approach for the precise, rapid, and dependable determination of CBD in products.
Gold Nanorod Density-Dependent Label-Free Bacteria Sensing on a Flake-like 3D Graphene-Based Device by SERS
Authors: Hossain Md Imran , Nanda Sitansu Sekhar , Cho Sooheon , Lee Bom , Kim Bum Jun , Choi Jae-Young , Yi Dong Kee
Published: October 2023

Surface-enhanced Raman spectroscopy (SERS) is an effective technique for biosensing, enabling label-free detection of biomolecules with enhanced sensitivity. There is a tremendous probability of signal failure in Raman frequencies because of the scattering of the Raman radiation in liquids, effective SERS improvement is required to reduce this issue when considering liquid specimens. We examined a liquid bacterial sample, investigating the electrostatic interactions of the bacterial samples with gold nanorods (AuNRs) and graphene. We established a voltage-gated 3D graphene functionalized with an AuNR-based device on the silicon substrate for SERS measurements when the applied voltage ranges from 0 to 3 V. Moreover, AuNRs density-susceptible bacterial sample analysis with varied concentrations of bacterial samples has also been described. Using bacterial SERS analysis, the bacterial components amide II (1555–1565 cm−1) and amide III (1250–1350 cm−1) have been discovered for both bacteria, Gram-positive, Listeria monocytogenes and Gram-negative, Salmonella typhi. Our fabricated device affords an interesting label-free, rapid, and reproducible bacterial sample analysis based on the density of the AuNRs when functionalizing flake-like 3D graphene, which can help facilitate label-free bacteria sensing platforms.
200 Years of Caprimulgid Records in Southern Brazil: A Comparison between the Literature and Citizen Science Data
Authors: Cavarzere Vagner
Published: October 2023

Although the ornithological history of southern Brazil has been amassed over the last 200 years, few attempts have been made to describe how species have accumulated. Furthermore, the collaboration of citizen scientists has considerably changed the way researchers analyze empirical data. Caprimulgidae (Nightjars and Nighthawks) species were used to illustrate how species have been recorded since the 1800s in Paraná State by comparing traditional and citizen science data. In addition, reports from both researchers and citizen scientists on the breeding biology of these caprimulgids have been verified. A literature review was conducted searching for the Caprimulgid species within the territory of Paraná. Regarding citizen science, records were obtained from four ornithological platforms. Overall, 14 species were detected within the state, 13 of which have been described in the literature, including 1 endemic to the Atlantic Forest and 3 threatened species. Citizen scientists detected all 13 taxa, in addition to one undocumented species that has never been recorded by researchers. There were 12 times more records on ornithological platforms in half of the sampling effort accumulated in studies, but most of them date from the last five years. Citizen scientists also visited 4.5 times more locations than researchers. Citizen scientists accumulated more records around September and November, and most (59%) records were from 2020–2022. Researchers mentioned species as early as 1820, while continuous studies only began during the 1980s; they concentrated their fieldwork mostly in September. Only one (2%) study sought to describe the breeding biology of a caprimulgid species, but there were 84 observations on ornithological platforms between 2004–2022 on their reproduction. Because of the evident mismatch between traditional and citizen science data due to a lack of congruence between their actions, it is suggested that ornithology in Paraná, as well as other Brazilian regions, would benefit the most if traditional and citizen scientists improved their networking communication to focus on common purposes instead of acting independently.
Rab Geranylgeranyltransferase Subunit Beta as a Potential Indicator to Assess the Progression of Amyotrophic Lateral Sclerosis
Authors: Yang Jing , Xin Cheng , Huo Jia , Li Xin , Dong Hui , Liu Qi , Li Rui , Liu Yaling
Published: October 2023

Background: Currently, there is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder. Many biomarkers have been proposed, but because ALS is a clinically heterogeneous disease with an unclear etiology, biomarker discovery for ALS has been challenging due to the lack of specificity of these biomarkers. In recent years, the role of autophagy in the development and treatment of ALS has become a research hotspot. In our previous studies, we found that the expression of RabGGTase (low RABGGTB expression and no change in RABGGTA) is lower in the lumbar and thoracic regions of spinal cord motoneurons in SOD1G93A mice compared with WT (wild-type) mice groups, and upregulation of RABGGTB promoted prenylation modification of Rab7, which promoted autophagy to protect neurons by degrading SOD1. Given that RabGGTase is associated with autophagy and autophagy is associated with inflammation, and based on the above findings, since peripheral blood mononuclear cells are readily available from patients with ALS, we proposed to investigate the expression of RabGGTase in peripheral inflammatory cells. Methods: Information and venous blood were collected from 86 patients diagnosed with ALS between January 2021 and August 2023. Flow cytometry was used to detect the expression of RABGGTB in monocytes from peripheral blood samples collected from patients with ALS and healthy controls. Extracted peripheral blood mononuclear cells (PBMCs) were differentiated in vitro into macrophages, and then the expression of RABGGTB was detected by immunofluorescence. RABGGTB levels in patients with ALS were analyzed to determine their impact on disease progression. Results: Using flow cytometry in monocytes and immunofluorescence in macrophages, we found that RABGGTB expression in the ALS group was significantly higher than in the control group. Age, sex, original location, disease course, C-reactive protein (CRP), and interleukin-6 (IL-6) did not correlate with the ALS functional rating scale—revised (ALSFRS-R), whereas the RABGGTB level was significantly correlated with the ALSFRS-R. In addition, multivariate analysis revealed a significant correlation between RABGGTB and ALSFRS-R score. Further analysis revealed a significant correlation between RABGGTB expression levels and disease progression levels (ΔFS). Conclusions: The RABGGTB level was significantly increased in patients with ALS compared with healthy controls. An elevated RABGGTB level in patients with ALS is associated with the rate of progression in ALS, suggesting that elevated RABGGTB levels in patients with ALS may serve as an indicator for tracking ALS progression.
Deepening Depression in Women Balancing Work–Life Responsibilities and Caregiving during the COVID-19 Pandemic: Findings from Gender-Specific Face-to-Face Street Interviews Conducted in Italy
Authors: Giusti Laura , Mammarella Silvia , Del Vecchio Sasha , Salza Anna , Casacchia Massimo , Roncone Rita
Published: October 2023

Purpose: This study investigated the impact of the COVID-19 pandemic on mental health, quality of life, and family functioning in a sample of the general female population, exploring difficulties encountered in managing family and work responsibilities and burden of care when taking care of a loved one. This study was, moreover, aimed at investigating factors capable of influencing severe depressive symptomatology in the context of socio-demographics, traumatic events, individual vulnerability, and family functioning. Method: The sampling method used in this research was non-probability sampling. The survey took place during a Hospital Open Weekend (8–10 October 2021) organized by the National Gender Observatory on Women’s Health “Fondazione Onda” on the occasion of the World Mental Health Day. Results: A total of 211 women were interviewed (mean age = 35.6, 53% living alone, more than 15% with financial difficulties, 47% exposed to the 2009 L’Aquila earthquake). More than 50% of the sample reported a higher complexity in managing their lives during the COVID-19 pandemic compared to their previous routine, with no statistically significant differences between working women and non-workers, although the latter obtained higher scores for depressive symptomatology and poorer quality of life. Compared to non-caregivers, female caregivers (22.3%) in charge of the care of loved ones affected by physical (10.9%) or psychiatric disabilities (11.4%) complained of a poorer quality of life, especially in general health perception (p = 0.002), physical function (p = 0.011), role limitations related to physical problems (p = 0.017), bodily pain (p = 0.015), mental health (p = 0.004), and social functioning (p = 0.007). Women caring for people affected by mental disorders seemed to experience a more significant worsening in vitality (p = 0.003) and social functioning (p = 0.005). Approximately 20% of the total sample reported severe depressive symptomatology. Previous access to mental health services (O.R. 10.923; p = 0.000), a low level of education (O.R. 5.410; p = 0.021), and difficulties in management of everyday lives during the COVID-19 pandemic (O.R. 3.598; p = 0.045) were found to be the main variables predictive of severe depressive psychopathology. Old age, good problem-solving skills, and ability to pursue personal goals were identified as protective factors. Conclusions: The COVID-19 pandemic underlined the need for support amongst emotionally vulnerable women with pre-existing mental health conditions, partly reflecting the cumulative effects of traumas.
Flexural Stiffness and Crack Width of Partially Prestressed Beams with Unbonded Tendons
Authors: Terán-Torres Bernardo T. , Elías-Chávez Adolfo A. , Valdez-Tamez Pedro L. , Rodríguez-Rodríguez Jose A. , Juárez-Alvarado César A.
Published: October 2023

The original concept of “Total Prestress” consists of creating compressions in concrete without generating tension stresses for service load, while in "Partially Prestressed” elements, tensions are allowed in the service stage, which would produce some cracking depending on applied loads that will be taken with non-prestressed reinforcement. Using criteria and design recommendations can guarantee maximum flexural capacity and admissible serviceability requirements of partially prestressed elements; however, there is insufficient research for estimating more accurately the required parameters for the design and review of these types of elements. Because of this, the present investigation consisted in the realization of experimental studies in continuous partially prestressed beams with unbonded tendons for the evaluation of the flexural behavior for different stages of load determining the actual stresses and the strains taking into account the structural stiffness decrease and its effect on deflections. The dimensions of the specimens were selected based on common dimensions presented on slabs. The tested specimens considered variables such as the relationship between the length of the continuous spans, the cross-section, and the partial prestressing ratio. Afterward, equations were proposed to predict the decrease in the structural stiffness, depending on the degree of cracking, the type of cross-section, the partial prestressing ratio, and the magnitude of the applied load and the tension and compression stresses to estimate the probable deflections for a particular loading stage. The crack width equation presented a difference of −16% to +18% with respect to the experimental data, while the flexural stiffness equation showed a highly accurate correlation to the experimental data.
Multi-Objective Optimization Design of FRP Reinforced Flat Slabs under Punching Shear by Using NGBoost-Based Surrogate Model
Authors: Liang Shixue , Cai Yiqing , Fei Zhengyu , Shen Yuanxie
Published: October 2023

Multi-objective optimization problems (MOPs) in structural engineering arise as a significant challenge in achieving a balance between prediction accuracy and efficiency of the surrogate models, which are conventionally adopted as mechanics-driven models or numerical models. Data-driven models, such as machine learning models, can be instrumental in resolving intricate structural engineering issues that cannot be tackled through mechanics-driven models. This study aims to address the challenges of multi-objective optimization punching shear design of fiber-reinforced polymer (FRP) reinforced flat slabs by using a data-driven surrogate model. Firstly, this study employs an advanced machine learning model, namely Natural Gradient Boosting (NGBoost), to predict the punching shear resistance of FRP reinforced flat slabs. The comparisons with other machine learning models, design provisions and empirical theory models illustrate that the NGBoost model has higher accuracy in predicting the punching shear resistance. Additionally, the NGBoost model is explained with Shapley Additive Explanation (SHAP), revealing that the slab’s effective depth is the primary factor affecting the punching shear resistance. Then, the formulated NGBoost model is adopted as a surrogate model in conjunction with the Non-Dominated Sorting Genetic Algorithm-II (NSGA-II) algorithm for multi-objective optimization design of FRP reinforced flat slabs subjected to punching shear. Through a case study, it is demonstrated that the Pareto-optimal set of the punching shear resistance and cost of the FRP reinforced flat slabs can be successfully obtained. By discussing the effects of design parameter changes on the results, it is also shown that increasing the slab’s effective depth is a relatively effective way to achieve higher punching shear resistance of FRP reinforced flat slabs.
Analysis and Optimized Location Selection of Comprehensive Green Space Supply in the Central Urban Area of Hefei Based on GIS
Authors: Huang Yunfeng , Yu Pengcheng , Xie Peng
Published: October 2023

Urban parks and green spaces are essential for improving the urban environment and enhancing ecological conditions. In this study, we utilize Geographic Information Systems (GIS) as a foundation to comprehensively evaluate the overall condition of park green spaces in Hefei city, taking into account factors, such as quantity (including area), quality, and accessibility. Additionally, we propose corresponding optimization site selection schemes. The results indicate that (1) the parks and green spaces in the central urban area of Hefei city are more accessible in the southern and western parts, while they are less accessible in the northern and eastern parts; (2) the green spaces in the Shushan area are not closely connected, and the parks are not developed in a related manner. In the Yaohai and Baohe areas, green spaces are in conflict, and the parks are developing at a slower pace. However, in the Luyang area, park green spaces are integrated and positively developed; (3) it is suggested that five new parks are added to the research area, and the locations of the newly added parks should be consistent with the results of the accessibility analysis, so that the selected locations are more reasonable.
Nonlinear Deformation Model for Analysis of Temperature Effects on Reinforced Concrete Beam Elements
Authors: Korsun Vladimir I. , Morozov Valeriy I. , Tamrazyan Ashot G. , Alekseytsev Anatoly V.
Published: October 2023

The results of the study are aimed at developing a nonlinear strain model for reinforced concrete beam elements in the general case of force actions and temperature effects for different durations. As a rule, temperature effects on structures involve temperature drops, causing heterogeneity of mechanical and rheological properties of concrete and reinforcement. The article has approximating expressions needed to take into account the effects of temperature and heating time on the values of temperature-induced strain and mechanical and rheological properties of heavy concretes with C30–C60 strength classes. The properties of concrete and rebars are heterogeneous from top to bottom and across the width of the cross section. A physically nonlinear problem is solved using the method of elastic solutions combined with the method of stepwise increases in temperature and force loading. The cooling of a heated reinforced concrete element to normal temperature is considered a short-term effect. Strength criteria of portions of a concrete cross section, crack closure conditions, and the ability of cracked sections to take loads in compression amid a change in the sign of stresses are determined. The stress–strain state (SSS) analysis of reinforced concrete beams, made according to the proposed method, is compared with the experimental studies using (i) values of thermal bending moments in statically indeterminate structures, (ii) cracking forces, and (iii) values of deformations (elongations and curvatures) of the elements in the longitudinal axis. Good agreement between the calculated and experimental values of controllable criteria confirms the reliability of physical relationships (i) developed for heterogeneous reinforced concrete beam elements and (ii) applied to the complex cases of temperature and force effects.
Risk-Informed, Reliability-Driven Decision Support for Building Basement Systems
Authors: Asmone Ashan Senel , Senarathne Helapura Nuwanshi Yasodara , Chew Michael Yit Lin
Published: October 2023

A lack of consideration for maintainability at the planning/design stage of a construction project often results in inadequate decision-making and selection of design alternatives, which will likely lead to unproductive operational regimes riddled with frequent defects. This paper attempts to anchor the quantitative risk analysis technique, Bayesian networks, as apt in predicting future operational defects based on the initial design alternatives by looking at specific case studies in building basement systems. Therefore, this paper aims to develop a comprehensive risk-informed, reliability-driven decision-making system. Central to this process is the implementation of a setup wherein a Bayesian Belief Network (BBN) operates as a powerful reliability engine. Concurrently, a risk matrix serves as a vital tool for facilitating risk-informed decision-making. This approach empowers stakeholders to make informed decisions regarding design choices while keeping maintainability at the forefront. It allows for maintainability to be practically used as an effective tool in buildings to lower the lifecycle cost. Furthermore, it is envisaged that this approach can be adopted in the construction industry globally for the prediction and diagnosis of defects, thereby facilitating risk-informed decision support. This study provides significant contributions to the building industry by providing a novel approach to a basement defect analysis, encouraging interdisciplinary collaboration among construction stakeholders, and assisting facility engineers and managers in properly determining maintenance requirements.
A Memetic Algorithm for the Solution of the Resource Leveling Problem
Authors: Iranagh Mehdi , Sonmez Rifat , Atan Tankut , Uysal Furkan , Bettemir Önder Halis
Published: October 2023

In this paper, we present a novel memetic algorithm (MA) for the solution of the resource leveling problem (RLP). The evolutionary framework of the MA is based on integration of a genetic algorithm and simulated annealing methods along with a resource leveling heuristic. The main objective of the proposed algorithm is to integrate complementary strengths of different optimization methods and incorporate the individual learning as a separate process for achieving a successful optimization method for the RLP. The performance of the MA is compared with the state-of-the-art leveling methods. For small instances up to 30 activities, mixed-integer linear models are presented for two leveling metrics to provide a basis for performance evaluation. The computational results indicate that the new integrated framework of the MA outperforms the state-of-the-art leveling heuristics and meta-heuristics and provides a successful method for the RLP. The limitations of popular commercial project management software are also illustrated along with the improvements achieved by the MA to reveal potential contributions of the proposed integrated framework in practice.
Reflective Façades: Revisiting a Neglected Trait of Modernism in Contemporary Architecture with New Implications and Significance
Authors: Elmoghazy Zeinab Ahmed Abd ElGhaffar , Afify Hazem M. Nour
Published: October 2023

Reflection and transparency are two valuable properties associated with the use of glass as an architectural material. While proponents of modernism favored transparency over reflection, whether in its physical or conceptual implications, to justify the designs of façades of Modernist buildings and in architectural criticism, contemporary architects are revisiting the neglected trait of ‘reflection’. Taking advantage of the technological advances in glass and other materials that have taken reflection to new limits, they are able to design reflective façades, providing new implications and significance. This paper aims to fill the theoretical gap that arises from the different conceptual ideas of using reflective façades. It will also explore the implications intended by architects to be perceived by viewers, thereby facilitating the future use of these façades in a way that satisfies architects and attracts beholders. The research methodology employed thematic analysis of various experiences of the use of reflective façades in different buildings with diverse functions and locations. The vocabulary used by architects and their intended implications were analyzed, coded, and categorized under three main themes: ‘Aesthetics of Disappearance’, ‘Games of Optical Illusions’, and ‘Mystery and Arousing Curiosity’.
Investigating Stakeholder Perspectives on the Knowledge Management of Construction Projects: A Case Study of the Vietnamese Construction Industry
Authors: Ulhaq Irfan , Maqsood Tayyab , Khalfan Malik , Le Tiendung , Rauf Abdul
Published: October 2023

Knowledge management (KM) is imperative for the successful completion of complex projects. This research, which constitutes a recent doctoral dissertation, centers on exploring the KM practices of internal project stakeholders in managing emergent events within construction projects during the construction stage. Herein, a qualitative approach was utilized. Twenty-five semi-structured interviews were conducted with experts from five internal project stakeholders. A thematic analysis was subsequently conducted using NVivo12 qualitative data analysis software. This study identified a total of eleven types of events categorized into four major themes. Furthermore, the analysis highlighted KM mechanisms applied by construction project stakeholders to overcome the events. In the emergent events context, personalization techniques, such as face-to-face meetings and discussions, are more effective for problem-solving. This study aims to enable Vietnamese construction companies to understand the importance of different KM mechanisms in the emergent events context and offers recommendations on effective KM.
The Adoption Intentions of Wearable Technology for Construction Safety
Authors: Chong Heap-Yih , Xu Yongshun , Lun Courtney , Chi Ming
Published: October 2023

Wearable technology (WT) is vital for proactive safety management. However, the adoption and use of WTs are very low when it comes to construction safety. This study proposes a hybrid model, combining elements of the technology acceptance model and the theory of planned behaviour model, with the aim of determining the factors predicting the adoption intention of WTs for construction safety. A mixed-method approach was used to test the model, namely the structural equation model (SEM) and fuzzy-set qualitative comparative analysis (fsQCA). The results show that no single predictor can significantly drive the adoption intention of all six WTs, namely smart wearable sensors, smart safety hats, smart safety vests, smart insoles, smart safety glasses, and smart wristbands, except for the uncovered effective combinations based on each WT individually. This research contributes to new insights into the antecedents of the adoption intention of WTs for construction safety, which are also useful for other technologies.
RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity
Authors: Guo Zhaoyu , Jiang Pei , Dong Qian , Zhang Yiming , Xu Kaikun , Zhai Yuanjun , He Fuchu , Tian Chunyan , Sun Aihua
Published: October 2023

Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment.
Molecular Signature of Endometrial Cancer with Coexistent Adenomyosis: A Multicentric Exploratory Analysis
Authors: Raimondo Diego , Raffone Antonio , Virgilio Agnese , Ferla Stefano , Maletta Manuela , Neola Daniele , Travaglino Antonio , Paradisi Roberto , Hernández Alicia , Spagnolo Emanuela , García-Pineda Virginia , Lenzi Jacopo , Guida Maurizio , Casadio Paolo , Seracchioli Renato
Published: October 2023

Adenomyosis has been associated with better survival outcomes in women with endometrial cancer. However, although the endometrial cancer patients’ risk stratification has been revolutionized by molecular findings, the impact of the molecular signature on the favorable prognosis of endometrial cancer patients with coexistent adenomyosis is unknown. The aim of our study was to compare the prevalence of molecular groups at poor and intermediate prognosis between endometrial cancer patients with and without coexistent adenomyosis. A multicentric, observational, retrospective, cohort study was performed to assess the differences in the prevalence of p53-abnormal expression (p53-abn) and mismatch repair protein-deficient expression (MMR-d) signatures between endometrial cancer patients with and without coexistent adenomyosis. A total of 147 endometrial cancer patients were included in the study: 38 in the adenomyosis group and 109 in the no adenomyosis group. A total of 37 patients showed the MMR-d signature (12 in the adenomyosis group and 25 in the no adenomyosis group), while 12 showed the p53-abn signature (3 in the adenomyosis group and 9 in the no adenomyosis group). No significant difference was found in the prevalence of p53-abn (p = 1.000) and MMR-d (p = 0.2880) signatures between endometrial cancer patients with and without coexistent adenomyosis. In conclusion, the molecular signature does not appear to explain the better prognosis associated with coexistent adenomyosis in endometrial cancer patients. Further investigation of these findings is necessary through future larger studies.
Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches
Authors: Cheng Xiaofei , Zhao Feng , Ke Bingxin , Chen Dong , Liu Fanlong
Published: October 2023

Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients.
Changes in the Epidemiology of Hepatocellular Carcinoma in Carinthia, Austria, 2012–2023
Authors: Hucke Florian , Emmer Heleen , Emmer Roberto , Hucke Miriam , Bota Simona , Fürstner Matthias , Hausegger Klaus , Mittermair Reinhard , Peck-Radosavljevic Markus
Published: October 2023

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths and remains a major burden on healthcare systems worldwide. The incidence of HCC continues to rise globally, despite preventative efforts being made. Aims: This study aimed to investigate epidemiological changes observed in the etiology and survival outcomes of HCC patients at Klinikum Klagenfurt am Wörthersee between 2012 and 2023. Methods: This was a retrospective, single-center cohort study. Two time-periods (2012–2017 and 2018–2023) were created to enable comparison between the respective intervals. IBM SPSS was used to analyze statistical data. Results: More patients were diagnosed with HCC during the second time period (n = 128, n = 148). The median age of diagnosis was 72.5 years (SD 8.6). Patients were on average 2 years younger in the second time period compared to the first (p = 0.042). Alcohol remained the leading underlying etiology of HCC and no statistically significant change was seen over time (p = 0.353). Nevertheless, a clear upward trend in the number of NASH cases was evident over time (n = 15, n = 28, respectively). Nearly half of the patient population had a normal AFP (<7 µg/L) level at the time of diagnosis (n = 116, 42.6%). The survival time for HCC patients remained similar between time periods, with a median overall survival time of 20.5 months (95% CI 16.8–24.2, p = 0.841), despite improvements in management strategies and the availability of new systemic treatments. More advanced-stage HCC cases were documented in the second period (BCLC-C, n = 23 to n = 46, p = 0.051). An increased number of HCC patients without liver cirrhosis were identified during the second time period (n = 22, n= 47, respectively, p = 0.005). NASH was the most common underlying etiology in patients without liver cirrhosis (50%) compared to alcohol use in being the primary cause in cirrhotic patients (65%, p < 0.001). Conclusion: HCC continues to be an important health concern in our society. The number of HCC patients without liver cirrhosis is steadily increasing, with NAFLD/NASH, due to underlying lifestyle diseases playing an important etiological role. Continued efforts should be made to prevent HCC and to screen at-risk population groups. Preventative strategies and screening techniques should be adjusted in light of the changing epidemiological landscape of HCC, where more focus will have to be placed on detecting HCC in patients without underlying cirrhosis.
A 15-Gene-Based Risk Signature for Predicting Overall Survival in SCLC Patients Who Have Undergone Surgical Resection
Authors: Atay Sevcan
Published: October 2023

Small cell lung cancer (SCLC) is a malignancy with a poor prognosis whose treatment has not progressed for decades. The survival benefit of surgery and the selection of surgical candidates are still controversial in SCLC. This study is the first report to identify transcriptomic alterations associated with prognosis and propose a gene expression-based risk signature that can be used to predict overall survival (OS) in SCLC patients who have undergone potentially curative surgery. An integrative transcriptome analysis of three gene expression datasets (GSE30219, GSE43346, and GSE149507) revealed 1734 up-regulated and 2907 down-regulated genes. Cox-Mantel test, Cox regression, and Lasso regression analyses were used to identify genes to be included in the risk signature. EGAD00001001244 and GSE60052-cohorts were used for internal and external validation, respectively. Overall survival was significantly poorer in patients with high-risk scores compared to the low-risk group. The discriminatory performance of the risk signature was superior to other parameters. Multivariate analysis showed that the risk signature has the potential to be an independent predictor of prognosis. The prognostic genes were enriched in pathways including regulation of transcription, cell cycle, cell metabolism, and angiogenesis. Determining the roles of the identified prognostic genes in the pathogenesis of SCLC may contribute to the development of new treatment strategies. The risk signature needs to be validated in a larger cohort of patients to test its usefulness in clinical decision-making.
Clinical Features and Outcomes of Conversion Therapy in Patients with Unresectable Hepatocellular Carcinoma
Authors: Tomonari Tetsu , Tani Joji , Sato Yasushi , Tanaka Hironori , Tanaka Takahiro , Taniguchi Tatsuya , Kawano Yutaka , Morishita Asahiro , Okamoto Koichi , Sogabe Masahiro , Miyamoto Hiroshi , Masaki Tsutomu , Takayama Tetsuji
Published: October 2023

This retrospective multicenter study analyzed 244 patients with unresectable hepatocellular carcinoma treated with lenvatinib (LEN) and atezolizumab + bevacizumab (Atezo + Bev) to examine the characteristics, treatment courses, and prognoses. The cases of patients who could achieve HCC downstaging from Barcelona Clinic Liver Cancer (BCLC) stage B or C to A or zero indicated the need for conversion therapy. The patients’ prognoses with and without conversion therapy were compared. Of the 244 patients, 12 (4.9%) underwent conversion therapy, six out of 131 (4.6%) were treated with LEN, and six out of 113 (5.3%) were treated with Atezo + Bev. Eleven patients (91.7%) with a modified albumin bilirubin (mALBI) grade 1 or 2a and BCLC-B stage showed significantly higher rates of transition during conversion therapy (p < 0.05). The patients undergoing conversion therapy had a significantly longer median overall survival rate than those receiving chemotherapy alone (1208 [1064–NA] vs. 569 [466–704] days, p < 0.01). A comparison of the patients who achieved a partial response with and without conversion was evaluated using propensity score matching to reduce the confounding factors, showing a significant survival benefit in the conversion group (1208 [1064–NA] vs. 665 days, p < 0.01). Among the patients with u-HCC who were treated with LEN and Atezo + Bev, those with mALBI 1 + 2a and BCLC-B were likely to achieve conversion therapy with downstaging.
Targeting Cytokines and Their Pathways for the Treatment of Cancer
Authors: Heimberger Amy B. , Tripathi Shashwat , Platanias Leonidas C.
Published: October 2023

This Special Issue focuses on the evolving role of immune modulatory cytokines, from their initial use as monotherapeutic recombinant proteins to their more contemporaneous use as modifiers for adoptive cellular immunotherapy [...]
Vacuum Ultraviolet (VUV) Light Photofunctionalization to Induce Human Oral Fibroblast Transmigration on Zirconia
Authors: Suzumura Toshikatsu , Matsuura Takanori , Komatsu Keiji , Sugita Yoshihiko , Maeda Hatsuhiko , Ogawa Takahiro
Published: October 2023

Soft tissue adhesion and sealing around dental and maxillofacial implants, related prosthetic components, and crowns are a clinical imperative to prevent adverse outcomes of periodontitis and periimplantitis. Zirconia is often used to fabricate implant components and crowns. Here, we hypothesized that UV treatment of zirconia would induce unique behaviors in fibroblasts that favor the establishment of a soft tissue seal. Human oral fibroblasts were cultured on zirconia specimens to confluency before placing a second zirconia specimen (either untreated or treated with one minute of 172 nm vacuum UV (VUV) light) next to the first specimen separated by a gap of 150 µm. After seven days of culture, fibroblasts only transmigrated onto VUV-treated zirconia, forming a 2.36 mm volume zone and 5.30 mm leading edge. Cells migrating on VUV-treated zirconia were enlarged, with robust formation of multidirectional cytoplastic projections, even on day seven. Fibroblasts were also cultured on horizontally placed and 45° and 60° tilted zirconia specimens, with the latter configurations compromising initial attachment and proliferation. However, VUV treatment of zirconia mitigated the negative impact of tilting, with higher tilt angles increasing the difference in cellular behavior between control and VUV-treated specimens. Fibroblast size, perimeter, and diameter on day seven were greater than on day one exclusively on VUV-treated zirconia. VUV treatment reduced surface elemental carbon and induced superhydrophilicity, confirming the removal of the hydrocarbon pellicle. Similar effects of VUV treatment were observed on glazed zirconia specimens with silica surfaces. One-minute VUV photofunctionalization of zirconia and silica therefore promotes human oral fibroblast attachment and proliferation, especially under challenging culture conditions, and induces specimen-to-specimen transmigration and sustainable photofunctionalization for at least seven days.
Distinct Mitotic Functions of Nucleolar and Spindle-Associated Protein 1 (NuSAP1) Are Controlled by Two Consensus SUMOylation Sites
Authors: Damizia Michela , Altieri Ludovica , Costanzo Vincenzo , Lavia Patrizia
Published: October 2023

Nucleolar and Spindle-Associated Protein 1 (NuSAP1) is an important mitotic regulator, implicated in control of mitotic microtubule stability and chromosome segregation. NuSAP1 regulates these processes by interacting with several protein partners. Its abundance, activity and interactions are therefore tightly regulated during mitosis. Protein conjugation with SUMO (Small Ubiquitin-like MOdifier peptide) is a reversible post-translational modification that modulates rapid changes in the structure, interaction(s) and localization of proteins. NuSAP1 was previously found to interact with RANBP2, a nucleoporin with SUMO ligase and SUMO-stabilizing activity, but how this interaction affects NuSAP1 activity has remained elusive. Here, we show that NuSAP1 interacts with RANBP2 and forms proximity ligation products with SUMO2/3 peptides in a RANBP2-dependent manner at key mitotic sites. A bioinformatic search identified two putative SUMO consensus sites in NuSAP1, within the DNA-binding and the microtubule-binding domains, respectively. Site-specific mutagenesis, and mitotic phenotyping in cell lines expressing each NuSAP1 mutant version, revealed selective roles of each individual site in control of NuSAP1 localization and in generation of specific mitotic defects and distinct fates in daughter cells. These results identify therefore two new regulatory sites for NuSAP1 functions and implicate RANBP2 in control of NuSAP1 activity.
Role of the Autism Risk Gene Shank3 in the Development of Atherosclerosis: Insights from Big Data and Mechanistic Analyses
Authors: Chang Hsiu-Wen , Hsu Ming-Jen , Chien Li-Nien , Chi Nai-Fang , Yu Meng-Chieh , Chen Hsiu-Chen , Lin Yuan-Feng , Hu Chaur-Jong
Published: October 2023

Increased medical attention is needed as the prevalence of autism spectrum disorder (ASD) rises. Both cardiovascular disorder (CVD) and hyperlipidemia are closely associated with adult ASD. Shank3 plays a key genetic role in ASD. We hypothesized that Shank3 contributes to CVD development in young adults with ASD. In this study, we investigated whether Shank3 facilitates the development of atherosclerosis. Using Gene Set Enrichment Analysis software (Version No.: GSEA-4.0.3), we analyzed the data obtained from Shank3 knockout mice (Gene Expression Omnibus database), a human population-based study cohort (from Taiwan’s National Health Insurance Research Database), and a Shank3 knockdown cellular model. Shank3 knockout upregulated the expression of genes of cholesterol homeostasis and fatty acid metabolism but downregulated the expression of genes associated with inflammatory responses. Individuals with autism had higher risks of hyperlipidemia (adjusted hazard ratio (aHR): 1.39; p < 0.001), major adverse cardiac events (aHR: 2.67; p < 0.001), and stroke (aHR: 3.55; p < 0.001) than age- and sex-matched individuals without autism did. Shank3 downregulation suppressed tumor necrosis factor-α-induced fatty acid synthase expression; vascular cell adhesion molecule 1 expression; and downstream signaling pathways involving p38, Jun N-terminal kinase, and nuclear factor-κB. Thus, Shank3 may influence the development of early-onset atherosclerosis and CVD in ASD. Furthermore, regulating Shank3 expression may reduce inflammation-related disorders, such as atherosclerosis, by inhibiting tumor necrosis factor-alpha-mediated inflammatory cascades.
Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer
Authors: Voutsadakis Ioannis A.
Published: October 2023

Metastatic colon cancer remains incurable despite improvements in survival outcomes. New therapies based on the discovery of colon cancer genomic subsets could improve outcomes. Colon cancers from genomic studies with publicly available data were examined to define the expression and regulation of the major tight junction proteins claudins and occludin in genomic groups. Putative regulations of the promoters of tight junction genes by colon-cancer-deregulated pathways were evaluated in silico. The effect of claudin mRNA expression levels on survival of colon cancer patients was examined. Common mutations in colon-cancer-related genes showed variable prevalence in genomically identified groups. Claudin genes were rarely mutated in colon cancer patients. Genomically identified groups of colon cancer displayed distinct regulation of claudins and occludin at the mRNA level. Claudin gene promoters possessed clustered sites of binding sequences for transcription factors TCF4 and SMADs, consistent with a key regulatory role of the WNT and TGFβ pathways in their expression. Although an effect of claudin mRNA expression on survival of colon cancer patients as a whole was not prominent, survival of genomic subsets was significantly influenced by claudin mRNA expression. mRNA expression of the main tight junction genes showed differential regulation in various genomically defined subgroups of colon cancer. These data pinpoint a distinct role of claudins and pathways that regulate them in these subgroups and suggest that subgroups of colon cancer should be considered in future efforts to therapeutically target claudins.
mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes
Authors: Garcia-Gaona Enrique , García-Gregorio Alhelí , García-Jiménez Camila , López-Olaiz Mildred Alejandra , Mendoza-Ramírez Paola , Fernandez-Guzman Daniel , Pillado-Sánchez Rolando Alberto , Soto-Pacheco Axel David , Yareni-Zuñiga Laura , Sánchez-Parada María Guadalupe , González-Santiago Ana Elizabeth , Román-Pintos Luis Miguel , Castañeda-Arellano Rolando , Hernández-Ortega Luis Daniel , Mercado-Sesma Arieh Roldán , Orozco-Luna Felipe de Jesús , Villa-Angulo Carlos , Villa-Angulo Rafael , Baptista-Rosas Raúl C.
Published: October 2023

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64–3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18–3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05–1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815–1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.