bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended Development of a Fission Gas Release Behavior Model Inside Spherical Fuel Grains for LWR Reactors
Authors: Guo Jingyu , Cheng Songbai , Wang Kai , Zhou Wenzhong
Published: September 2023

Fission gas plays a significant role in fuel rod performance following accidents. The amount of fission gas increases dramatically under accidental conditions. This leads to a subsequent rise in the fuel rod internal pressure and temperature due to aggravated gap conductance between the fuel pellet and cladding. As a result, fuel rod performance degrades. Therefore, studying fission gas behavior is crucial for accident assessment and evaluating fuel rod performance. Minimizing the Impact of fission gas on fuel rods is essential for maintaining their integrity and safety within nuclear reactors. One important aspect of ensuring safety is predicting fission gas release (FGR). In this study, we presented an extended model to be used in light water reactors (LWRs). The FGR can be modeled using COMSOL Multiphysics with the finite element method. This modeling approach considers both normal and abnormal conditions, with the latter categorized as Class-II type incidents. The model assumes that the gas diffusion inside a spherical grain varies over time. By examining perfect sinks with gas production, perfect sinks without gas production, and imperfect sinks under steady-state conditions, different initial and boundary conditions are set. To validate the accuracy and universality of expressions used in the model, input parameters from other models and experiments are utilized. By comparing the model’s results with these inputs, the accuracy and applicability of the expressions can be confirmed. This validation process ensures that the model provides reliable predictions for fission gas behavior in fuel rods under both normal and abnormal operating conditions. Based on our findings, it is evident that the FGR fraction displays an upward trend as diffusion coefficients and temperatures rise. Conversely, larger grain sizes and higher linear heat generation rates are associated with a reduction in the FGR fraction. Notably, enhanced resolution leads to a postponed onset of FGR. Furthermore, the influence of the diffusion coefficient on the FGR fraction primarily stems from the interconnected effects of temperature and linear heat generation rate.
Global Fixed-Time Sliding Mode Trajectory Tracking Control Design for the Saturated Uncertain Rigid Manipulator
Authors: Nie Jun , Hao Lichao , Lu Xiao , Wang Haixia , Sheng Chunyang
Published: September 2023

The global fixed-time sliding mode control strategy is designed for the manipulator to achieve global fixed-time trajectory tracking in response to the uncertainty of the system model, the external disturbances, and the saturation of the manipulator actuator. First, aiming at the lumped disturbance caused by system model uncertainty and external disturbance, the adaptive fixed-time sliding mode disturbance observer (AFSMDO) was introduced to eliminate the negative effects of disturbance. The observer parameters can adaptively change with disturbances by designing the adaptive law, improving the accuracy of disturbance estimation. Secondly, the fixed-time sliding surface was introduced to avoid singularity, and the nonsingular fixed-time sliding mode control (NFSMC) design was put in place to ensure the global convergence of the manipulator system. Finally, the fixed time saturation compensator (FTSC) was created for NFSMC to prevent the negative impact of actuator saturation on the manipulator system, effectively reducing system chatter and improving the response speed of the closed-loop system. The fixed-time stability theory and Lyapunov method were exploited to offer a thorough and rigorous theoretical analysis and stability demonstration for the overall control system. Simulation experiments verify that the designed control scheme has excellent control effects and strong practicability.
Derivation of Bounds for Majorization Differences by a Novel Method and Its Applications in Information Theory
Authors: Basir Abdul , Khan Muhammad Adil , Ullah Hidayat , Almalki Yahya , Chasreechai Saowaluck , Sitthiwirattham Thanin
Published: September 2023

In the recent era of research developments, mathematical inequalities and their applications perform a very consequential role in different aspects, and they provide an engaging area for research activities. In this paper, we propose a new approach for the improvement of the classical majorization inequality and its weighted versions in a discrete sense. The proposed improvements give several estimates for the majorization differences. Some earlier improvements of the Jensen and Slater inequalities are deduced as direct consequences of the obtained results. We also discuss the conditions under which the main results give better estimates for the majorization differences. Applications of the acquired results are also presented in information theory.
Numerical Solution of Nonlinear Backward Stochastic Volterra Integral Equations
Authors: Samar Mahvish , Yao Kutorzi , Zhu Xinzhong
Published: September 2023

This work uses the collocation approximation method to solve a specific type of backward stochastic Volterra integral equations (BSVIEs). Using Newton’s method, BSVIEs can be solved using block pulse functions and the corresponding stochastic operational matrix of integration. We present examples to illustrate the estimate analysis and to demonstrate the convergence of the two approximating sequences separately. To measure their accuracy, we compare the solutions with values of exact and approximative solutions at a few selected locations using a specified absolute error. We also propose an efficient method for solving a triangular linear algebraic problem using a single integral equation. To confirm the effectiveness of our method, we conduct numerical experiments with issues from real-world applications.
Performance Evaluation of Renewable Energy Systems: Photovoltaic, Wind Turbine, Battery Bank, and Hydrogen Storage
Authors: Lazaroiu Gheorghe , Gmal Osman Mohammed , Strejoiu Cristian-Valentin
Published: September 2023

The analysis aims to determine the most efficient and cost-effective way of providing power to a remote site. The two primary sources of power being considered are photovoltaics and small wind turbines, while the two potential storage media are a battery bank and a hydrogen storage fuel cell system. Subsequently, the hydrogen is stored within a reservoir and employed as required by the fuel cell. This strategy offers a solution for retaining surplus power generated during peak production phases, subsequently utilizing it during periods when the renewable power sources are generating less power. To evaluate the performance of the hydrogen storage system, the analysis included a sensitivity analysis of the wind speed and the cost of the hydrogen subsystem. In this analysis, the capital and replacement costs of the electrolyzer and hydrogen storage tank were linked to the fuel cell capital cost. As the fuel cell cost decreases, the cost of the electrolyzer and hydrogen tank also decreases. The optimal system type graph showed that the hydrogen subsystem must significantly decrease in price to become competitive with the battery bank.
Implementing a Synchronization Method between a Relational and a Non-Relational Database
Authors: Győrödi Cornelia A. , Turtureanu Tudor , Győrödi Robert Ş. , Zmaranda Doina R.
Published: September 2023

The accelerating pace of application development requires more frequent database switching, as technological advancements demand agile adaptation. The increase in the volume of data and at the same time, the number of transactions has determined that some applications migrate from one database to another, especially from a relational database to a non-relational (NoSQL) alternative. In this transition phase, the coexistence of both databases becomes necessary. In addition, certain users choose to keep both databases permanently updated to exploit the individual strengths of each database in order to streamline operations. Existing solutions mainly focus on replication, failing to adequately address the management of synchronization between a relational and a non-relational (NoSQL) database. This paper proposes a practical IT approach to this problem and tests the feasibility of the proposed solution by developing an application that maintains the synchronization between a MySQL database as a relational database and MongoDB as a non-relational database. The performance and capabilities of the solution are analyzed to ensure data consistency and correctness. In addition, problems that arose during the development of the application are highlighted and solutions are proposed to solve them.
Innovations in Sparkling Wine Production: A Review on the Sensory Aspects and the Consumer’s Point of View
Authors: Cravero Maria
Published: September 2023

Sparkling wines have a relevant economic value, and they are mostly produced worldwide with the Traditional method (in bottles) or with the Charmat method (in autoclaves). Many varieties are employed in different viticultural areas to obtain white or rosé wines and red (Italy and Australia), with different sugar content. This review illustrates the most recent studies (last 5 years) on sparkling wines concerning innovative yeasts, aromatic profile, aging on lees, sugar types, base wine, new varieties, and innovative oenological techniques, which consider the effects on the sensory characteristics and the consumer preferences.
Ocean Acidification Affects the Response of the Coastal Coccolithophore Pleurochrysis carterae to Irradiance
Authors: Wu Fengxia , Guo Jia , Duan Haozhen , Li Tongtong , Wang Yanan , Wang Yuntao , Wang Shiqiang , Feng Yuanyuan
Published: September 2023

The ecologically important marine phytoplankton group coccolithophores have a global distribution. The impacts of ocean acidification on the cosmopolitan species Emiliania huxleyi have received much attention and have been intensively studied. However, the species-specific responses of coccolithophores and how these responses will be regulated by other environmental drivers are still largely unknown. To examine the interactive effects of irradiance and ocean acidification on the physiology of the coastal coccolithophore species Pleurochrysis carterae, we carried out a semi-continuous incubation experiment under a range of irradiances (50, 200, 500, 800 μmol photons m−2 s−1) at two CO2 concentration conditions of 400 and 800 ppm. The results suggest that the saturation irradiance for the growth rate was higher at an elevated CO2 concentration. Ocean acidification weakened the particulate organic carbon (POC) production of Pleurochrysis carterae and the inhibition rate was decreased with increasing irradiance, indicating that ocean acidification may affect the tolerating capacity of photosynthesis to higher irradiance. Our results further provide new insight into the species-specific responses of coccolithophores to the projected ocean acidification under different irradiance scenarios in the changing marine environment.
Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
Authors: Han Suyeon , Choi Hyunsu , Park Hyerim , Kim Jwa-Jin , Lee Eu-Jin , Ham Young-Rok , Na Ki-Rayng , Lee Kang-Wook , Chang Yoon-Kyung , Choi Dae-Eun
Published: September 2023

The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, we assessed the efficacy of ω3-PUFAs in attenuating UUO injury and investigated their mechanism of action. The immortalized human proximal tubular cells human kidney-2 (HK2) were incubated for 72 h with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in various concentrations, in the presence or absence of transforming growth factor (TGF)-β. DHA/EPA reduced the epithelial–mesenchymal transition in the TGF-β-treated HK2 cells by enhancing autophagy flux and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. C57BL/6 mice were divided into four groups and treated as follows: sham (no treatment, n = 5), sham + ω3-PUFAs (n = 5), UUO (n = 10), and UUO + ω3-PUFAs (n = 10). Their kidneys and blood were harvested on the seventh day following UUO injury. The kidneys of the ω3-PUFAs-treated UUO mice showed less oxidative stress, inflammation, and fibrosis compared to those of the untreated UUO mice. Greater autophagic flux, higher amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7, lower amounts of p62, and higher levels of cathepsin D and ATP6E were observed in the kidneys of the omega-3-treated UUO mice compared to those of the control UUO mice. In conclusion, ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury.
Biomarkers in Pain
Authors: Larsson Anders , Bäckryd Emmanuel , Eriksson Mats
Published: September 2023

The focus of this Special Issue on Biomedicines is on the value of “Biomarkers in Pain” from a broad perspective [...]
Regulation of Soluble E-Cadherin Signaling in Non-Small-Cell Lung Cancer Cells by Nicotine, BDNF, and β-Adrenergic Receptor Ligands
Authors: Ray Ravel , Goel Stuti , Al Khashali Hind , Darweesh Ban , Haddad Ben , Wozniak Caroline , Ranzenberger Robert , Khalil Jeneen , Guthrie Jeffrey , Heyl Deborah , Evans Hedeel Guy
Published: September 2023

The ectodomain of the transmembrane protein E-cadherin can be cleaved and released in a soluble form referred to as soluble E-cadherin, or sE-cad, accounting for decreased E-cadherin levels at the cell surface. Among the proteases implicated in this cleavage are matrix metalloproteases (MMP), including MMP9. Opposite functions have been reported for full-length E-cadherin and sE-cad. In this study, we found increased MMP9 levels in the media of two non-small cell lung cancer (NSCLC) cell lines, A549 and H1299, treated with BDNF, nicotine, or epinephrine that were decreased upon cell treatment with the β-adrenergic receptor blocker propranolol. Increased MMP9 levels correlated with increased sE-cad levels in A549 cell media, and knockdown of MMP9 in A549 cells led to downregulation of sE-cad levels in the media. Previously, we reported that A549 and H1299 cell viability increased with nicotine and/or BDNF treatment and decreased upon treatment with propranolol. In investigating the function of sE-cad, we found that immunodepletion of sE-cad from the media of A549 cells untreated or treated with BDNF, nicotine, or epinephrine reduced activation of EGFR and IGF-1R, decreased PI3K and ERK1/2 activities, increased p53 activation, decreased cell viability, and increased apoptosis, while no effects were found using H1299 cells under all conditions tested.
Immobilization of Enzyme Electrochemical Biosensors and Their Application to Food Bioprocess Monitoring
Authors: Sun Ganchao , Wei Xiaobo , Zhang Dianping , Huang Liben , Liu Huiyan , Fang Haitian
Published: September 2023

Electrochemical biosensors based on immobilized enzymes are among the most popular and commercially successful biosensors. The literature in this field suggests that modification of electrodes with nanomaterials is an excellent method for enzyme immobilization, which can greatly improve the stability and sensitivity of the sensor. However, the poor stability, weak reproducibility, and limited lifetime of the enzyme itself still limit the requirements for the development of enzyme electrochemical biosensors for food production process monitoring. Therefore, constructing sensing technologies based on enzyme electrochemical biosensors remains a great challenge. This article outlines the construction principles of four generations of enzyme electrochemical biosensors and discusses the applications of single-enzyme systems, multi-enzyme systems, and nano-enzyme systems developed based on these principles. The article further describes methods to improve enzyme immobilization by combining different types of nanomaterials such as metals and their oxides, graphene-related materials, metal–organic frameworks, carbon nanotubes, and conducting polymers. In addition, the article highlights the challenges and future trends of enzyme electrochemical biosensors, providing theoretical support and future perspectives for further research and development of high-performance enzyme chemical biosensors.
Physical Activity and Quality of Life among People with Intellectual Disabilities: The Role of Gender and the Practice Characteristics
Authors: Franco Evelia , Ocete Carmen , Pérez-Calzado Elena , Berástegui Ana
Published: September 2023

Staying physically active is synonymous with good health and well-being, and its benefits on the health of people with intellectual disabilities (PWIDs) have been studied. However, there is a lack of information on how it can influence their quality of life (QoL). This study aimed to analyze the relationship between QoL and physical activity in PWIDs according to gender and the characteristics of the practiced activity. A questionnaire was administered to 380 PWIDs (mean age of 28.23 ± 12.53), 54.21% of which were men. The QoL dimensions and second-order factors were studied in relation to practicing physical activity, the practice type, the context, and gender. The results indicate that people who practiced any activity showed better QoL values. Those who engaged in a nonregulated physical activity had better values in self-determination, emotional well-being, social inclusion, and personal development, while those who did sports presented higher scores in interpersonal relationships and physical well-being. In addition, it also appears that the association between physical activity and the QoL dimensions is distinct in inclusive and specific contexts. In conclusion, physical activity is related to a better QoL, although the impact of the practice type and context differs for each QoL dimension.
Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance
Authors: Kiełb Paweł , Kaczorowski Maciej , Kowalczyk Kamil , Piotrowska Aleksandra , Nowak Łukasz , Krajewski Wojciech , Chorbińska Joanna , Dudek Krzysztof , Dzięgiel Piotr , Hałoń Agnieszka , Szydełko Tomasz , Małkiewicz Bartosz
Published: September 2023

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found—expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications.
Development and Validation of Pretreatment Serum Total Bilirubin as a Biomarker to Predict the Clinical Outcomes in Primary Central Nervous System Lymphoma: A Multicenter Cohort Study
Authors: Cao Jiazhen , Li Shengjie , Li Danhui , Hua Wei , Guo Lin , Xia Zuguang
Published: September 2023

Primary central nervous system lymphoma (PCNSL) is a predominantly aggressive neoplasm isolated to the central nervous system or vitreoretinal space. Bilirubin is an important biomarker reflecting hepatic function and oxidative stress status that is associated with the occurrence and development of various tumors. However, its prognostic role in PCNSL has yet to be evaluated. Therefore, we conducted a prospective–retrospective study to analyze the predictive value of serum total bilirubin (STB) in PCNSL patients. The association between the pretreatment STB and clinical outcomes in PCNSL was developed in the discovery cohort (retrospective [n = 44] and prospective [n = 45]) and validated in an independent retrospective cohort (n = 69). A generalized additive model, Kaplan–Meier curve, and Cox analysis were applied. In the discovery cohort, the STB showed a linear relationship with overall survival (OS, p = 0.011) and progression-free survival (PFS, p = 0.0476). The median STB level of 12.0 µmol/L was determined as the cutoff value to predict the clinical outcomes with area under the receiver operating characteristic curve (AUROC) values of 0.9205 and 0.8464 for OS and PFS, respectively. The median STB level resulted in similar accuracy for predicting the clinical outcomes in the validation cohort with AUROC values of 0.8857 and 0.8589 for OS and PFS, respectively. In both the discovery and validation cohorts, the Kaplan–Meier survival curve and Cox regression analysis showed that the upper median STB groups showed significantly worse OS than the lower median STB groups. In conclusion, the pretreatment STB could be considered a novel biomarker to predict the clinical outcomes in patients with PCNSL receiving high-dose methotrexate-based combination immunochemotherapy.
Minimally Invasive Radical Nephroureterectomy: 5-Year Update of Techniques and Outcomes
Authors: Franco Antonio , Ditonno Francesco , Feng Carol , Manfredi Celeste , Sturgis Morgan R. , Farooqi Mustafa , Del Giudice Francesco , Coogan Christopher , Ferro Matteo , Zhang Chao , Wu Zhenjie , Yang Bo , Wang Linhui , Autorino Riccardo
Published: September 2023

The gold standard treatment for non-metastatic upper tract urothelial cancer (UTUC) is represented by radical nephroureterectomy (RNU). The choice of surgical technique in performing UTUC surgery continues to depend on several factors, including the location and extent of the tumor, the patient’s overall health, and very importantly, the surgeon’s skill, experience, and preference. Although open and laparoscopic approaches are well-established treatments, evidence regarding robot-assisted radical nephroureterectomy (RANU) is growing. Aim of our study was to perform a critical review on the evidence of the last 5 years regarding surgical techniques and outcomes of minimally invasive RNU, mostly focusing on RANU. Reported oncological and function outcomes suggest that minimally invasive RNU is safe and effective, showing similar survival rates compared to the open approach.
The Impact of Drug–Drug Interactions on the Toxicity Profile of Combined Treatment with BRAF and MEK Inhibitors in Patients with BRAF-Mutated Metastatic Melanoma
Authors: Mezi Silvia , Botticelli Andrea , Scagnoli Simone , Pomati Giulia , Fiscon Giulia , De Galitiis Federica , Di Pietro Francesca Romana , Verkhovskaia Sofia , Amirhassankhani Sasan , Pisegna Simona , Gentile Giovanna , Simmaco Maurizio , Gohlke Bjoern , Preissner Robert , Marchetti Paolo
Published: September 2023

Background: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug–drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy. Methods: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23). The association between the Drug-PIN continuous score or the Drug-PIN traffic light and the occurrence of treatment-related toxicities and oncological outcomes was evaluated. Results: In total, 177 patients with advanced BRAF-mutated melanoma undergoing BRAF/MEK targeted therapy were included. All grade toxicity was registered in 79% of patients. Cardiovascular toxicities occurred in 31 patients (17.5%). Further, 94 (55.9%) patients had comorbidities requiring specific pharmacological treatments. The median Drug-PIN score significantly increased when the target combination was added to the patient’s home therapy (p-value < 0.0001). Cardiovascular toxicity was significantly associated with the Drug-PIN score (p-value = 0.048). The Drug-PIN traffic light (p = 0.00821) and the Drug-PIN score (p = 0.0291) were seen to be significant predictors of cardiotoxicity. Patients with low-grade vs. high-grade interactions showed a better prognosis regarding overall survival (OS) (p = 0.0045) and progression-free survival (PFS) (p = 0.012). The survival analysis of the subgroup of patients with cardiological toxicity demonstrated that patients with low-grade vs. high-grade DDIs had better outcomes in terms of OS (p = 0.0012) and a trend toward significance in PFS (p = 0.068). Conclusions: DDIs emerged as a critical issue for the risk of treatment-related cardiovascular toxicity. Our findings support the utility of DDI assessment in melanoma patients treated with BRAF/MEK inhibitors.
A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients
Authors: Gomez-Rosas Patricia , Giaccherini Cinzia , Russo Laura , Verzeroli Cristina , Gamba Sara , Tartari Carmen Julia , Bolognini Silvia , Ticozzi Chiara , Schieppati Francesca , Barcella Luca , Sarmiento Roberta , Masci Giovanna , Tondini Carlo , Petrelli Fausto , Giuliani Francesco , D’Alessio Andrea , Minelli Mauro , De Braud Filippo , Santoro Armando , Labianca Roberto , Gasparini Giampietro , Marchetti Marina , Falanga Anna ,   on behalf of the HYPERCAN Investigators
Published: September 2023

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.
Predictors of PSMA PET Positivity: Analysis in a Selected Cohort of Biochemical Recurrence Prostate Cancer Patients after Radical Prostatectomy
Authors: Mapelli Paola , Ghezzo Samuele , Pini Cristiano , Samanes Gajate Ana Maria , Spataro Alessandro , Bezzi Carolina , Landoni Claudio , Scifo Paola , Briganti Alberto , Chiti Arturo , Picchio Maria
Published: September 2023

Localized prostate cancer (PCa) can be treated with radical prostatectomy (RP). Up to 30% of patients undergoing this procedure experience biochemical recurrence (BCR), namely the rise in serum prostate-specific antigen (PSA) levels during the post-surgical follow-up, requiring further treatments and with the risk of severe disease progression. Currently, the most accurate imaging technique to confirm, detect, and locate disease relapses in BCR patients is prostate-specific membrane antigen (PSMA)-targeted PET, as recommended by international clinical guidelines. The aim of the study was to investigate potential clinical and pathological predictors of PSMA PET positivity, validated by clinical and instrumental follow-up or histopathological data. In this study, a selected cohort of BCR patients after RP and no other PCa-related therapy who underwent either PSMA PET/CT or PSMA PET/MRI has been analysed. Among the considered predictors, both pathological staging after RP equal or higher than pT3a and higher PSA levels at the time of the scan were significantly correlated with PSMA PET positivity on multivariate logistic regression analysis. As expected, PSMA PET confirmed its role as an accurate imaging technique in the setting of BCR in PCa. These findings may inform appropriate and tailored patient selection and scan timing to optimize and fully exploit this powerful diagnostic tool.
Characterization of an Mtbp Hypomorphic Allele in a Diethylnitrosamine-Induced Liver Carcinogenesis Model
Authors: Ranjan Atul , Thoenen Elizabeth A. , Kaida Atsushi , Wood Stephanie , Van Dyke Terry , Iwakuma Tomoo
Published: September 2023

MTBP is implicated in cell cycle progression, DNA replication, and cancer metastasis. However, the function of MTBP remains enigmatic and is dependent on cellular contexts and its cellular localization. To understand the in vivo physiological role of MTBP, it is important to generate Mtbp knockout mice. However, complete deletion of the Mtbp gene in mice results in early embryonic lethality, while its heterozygous deletion shows modest biological phenotypes, including enhanced cancer metastasis. To overcome this and better characterize the in vivo physiological function of MTBP, we, for the first time, generated mice that carry an Mtbp hypomorphic allele (MtbpH) in which Mtbp protein is expressed at approximately 30% of that in the wild-type allele. We treated wild-type, Mtbp+/−, and MtbpH/− mice with a liver carcinogen, diethylnitrosamine (DEN), and found that the MtbpH/− mice showed worse overall survival when compared to the wild-type mice. Consistent with previous reports using human liver cancer cells, mouse embryonic fibroblasts (MEFs) from the MtbpH/− mice showed an increase in the nuclear localization of p-Erk1/2 and migratory potential. Thus, MtbpH/− mice and cells from MtbpH/− mice are valuable to understand the in vivo physiological role of Mtbp and validate the diverse functions of MTBP that have been observed in human cells.
Improved Rate of Negative Margins for Inflammatory Breast Cancer Using Intraoperative Frozen Section Analysis
Authors: Kong Joshua , Bandyopadhyay Sudeshna , Chen Wei , Al-Mufarrej Faisal , Choi Lydia , Kosir Mary A.
Published: September 2023

Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer with a poor survival rate. Modified radical mastectomy (MRM) with negative pathologic margins is critical for improved survival. We aim to study the potential benefit of intraoperative frozen section analysis (FSA) to improve disease-free margins. Methods: This prospective, monocentric study included 19 patients who underwent MRM for IBC. For each patient, a 2 mm continuous skin edge was sent for FSA to guide further resection. The rate of tumor-free margins and the concurrence between the FSA and permanent pathological results were analyzed. Results: Overall, 15 of the 19 patients achieved negative margins, including four patients who would have had positive margins without FSA. The odds ratio of achieving a negative final margin with FSA was infinity (p = 0.031), and there was a strong agreement between the FSA and permanent pathological results (Kappa—0.83; p < 0.0001). Conclusions: The FSA technique decreased the number of positive margins in IBC patients undergoing MRM, thereby potentially reducing the need for re-operation, allowing immediate wound closure, and preventing delays in the administration of adjuvant radiation therapy. More extensive trials are warranted to establish the use of intraoperative FSA in IBC treatment.
Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development
Authors: Yuan Ye , Alzrigat Mohammad , Rodriguez-Garcia Aida , Wang Xueyao , Bexelius Tomas Sjöberg , Johnsen John Inge , Arsenian-Henriksson Marie , Liaño-Pons Judit , Bedoya-Reina Oscar C.
Published: September 2023

Deregulation of the MYC family of transcription factors c-MYC (encoded by MYC), MYCN, and MYCL is prevalent in most human cancers, with an impact on tumor initiation and progression, as well as response to therapy. In neuroblastoma (NB), amplification of the MYCN oncogene and over-expression of MYC characterize approximately 40% and 10% of all high-risk NB cases, respectively. However, the mechanism and stage of neural crest development in which MYCN and c-MYC contribute to the onset and/or progression of NB are not yet fully understood. Here, we hypothesized that subtle differences in the expression of MYCN and/or c-MYC targets could more accurately stratify NB patients in different risk groups rather than using the expression of either MYC gene alone. We employed an integrative approach using the transcriptome of 498 NB patients from the SEQC cohort and previously defined c-MYC and MYCN target genes to model a multigene transcriptional risk score. Our findings demonstrate that defined sets of c-MYC and MYCN targets with significant prognostic value, effectively stratify NB patients into different groups with varying overall survival probabilities. In particular, patients exhibiting a high-risk signature score present unfavorable clinical parameters, including increased clinical risk, higher INSS stage, MYCN amplification, and disease progression. Notably, target genes with prognostic value differ between c-MYC and MYCN, exhibiting distinct expression patterns in the developing sympathoadrenal system. Genes associated with poor outcomes are mainly found in sympathoblasts rather than in chromaffin cells during the sympathoadrenal development.
Sarcopenia Diagnosis and Management in Hematological Malignancies and Differences with Cachexia and Frailty
Authors: Colloca Giuseppe Ferdinando , Bellieni Andrea , Di Capua Beatrice , Iervolino Marialuisa , Bracci Serena , Fusco Domenico , Tagliaferri Luca , Landi Francesco , Valentini Vincenzo
Published: September 2023

Sarcopenia is a geriatric syndrome characterized by a progressive loss of systemic muscle mass and decreased muscle strength or physical function. Several conditions have a role in its pathogenesis, significantly impacting adverse outcomes such as falls, functional decline, frailty, disability, multiple hospitalizations, and mortality. In the oncological setting, sarcopenia is associated with an increased risk of treatment toxicity, postoperative complications, and a higher mortality rate related to other causes (e.g., pneumonia). In the hematological field, even more so, sarcopenia predicts toxicity and response to treatments. In patients with hematologic malignancy, low muscle mass is associated with adverse outcomes and is a predictor of overall survival and non-relapse mortality. Therefore, it is essential to correctly recognize sarcopenia, evaluate the risk factors and their impact on the patient’s trajectory, and effectively treat sarcopenia. Sarcopenia is a reversible condition. The most effective intervention for reversing it is physical exercise combined with nutrition. The objective of clinical assessment focused on sarcopenia is to be able to carry out a “tailor-made treatment”.
Three Dimensional Models of Endocrine Organs and Target Tissues Regulated by the Endocrine System
Authors: Luca Edlira , Zitzmann Kathrin , Bornstein Stefan , Kugelmeier Patrick , Beuschlein Felix , Nölting Svenja , Hantel Constanze
Published: September 2023

Immortalized cell lines originating from tumors and cultured in monolayers in vitro display consistent behavior and response, and generate reproducible results across laboratories. However, for certain endpoints, these cell lines behave quite differently from the original solid tumors. Thereby, the homogeneity of immortalized cell lines and two-dimensionality of monolayer cultures deters from the development of new therapies and translatability of results to the more complex situation in vivo. Organoids originating from tissue biopsies and spheroids from cell lines mimic the heterogeneous and multidimensional characteristics of tumor cells in 3D structures in vitro. Thus, they have the advantage of recapitulating the more complex tissue architecture of solid tumors. In this review, we discuss recent efforts in basic and preclinical cancer research to establish methods to generate organoids/spheroids and living biobanks from endocrine tissues and target organs under endocrine control while striving to achieve solutions in personalized medicine.
Oral Cavity Cancer Tissues Differ in Isotopic Composition Depending on Location and Staging
Authors: Bogusiak Katarzyna , Kozakiewicz Marcin , Puch Aleksandra , Mostowski Radosław , Paneth Piotr , Kobos Józef
Published: September 2023

The aim of this paper was to characterise the isotopic composition of oral squamous cell carcinoma (OSCC) specimens of different areas of the oral cavity. Secondly, we assessed whether there was a correlation between clinical stages of OSCC and isotopic abundance. The IRMS procedure was performed on 124 samples derived from 31 patients with OSCC of 15 N and 13 C to assess the isotopic composition. From each individual, four samples from the tumour, two from the margins, and two samples of healthy oral mucous membranes were derived. The two samples from the tumour and two samples from the margin were additionally subjected to histopathological assessment. Then, statistical analysis was conducted. Tumour infiltration tissues of the lower lip were characterised by higher mean δ13C values compared to samples derived from cancers of the other oral cavity regions (−23.82 ± 1.21 vs. −22.67 ± 1.35); (p = 0.04). The mean percentage of nitrogen content in tumour tissues was statistically higher in patients with the most advanced cancers (11.89 ± 0.03%) versus the group of patients with II and III stage cancers (11.12 ± 0.02%); (p = 0.04). In patients at stage IV, the mean δ13C value in the cancer samples equalled −22.69 ± 1.42 and was lower than that in patients at less severe clinical stages (p = 0.04). Lower lip cancer tissues differed in the isotopic abundance of carbon in comparison with tissues derived from the group of combined samples from other locations. Values of δ13C observed in specimens derived from lower lip cancers were similar to those observed in healthy oral mucous membranes. Cancer tissues obtained from patients in the last stage of OSCC had a different isotopic composition in comparison with those obtained from earlier stages. To confirm these observations, further research on larger groups of patients is needed.
The Epidemiological Pattern of Skin Cancer from 2011 to 2022 among the Population of the Aseer Region, Kingdom of Saudi Arabia
Authors: Algarni Abdullah Mohammed , Alshehri Hamza Salim , Al Zomia Ahmed Saad , Alhifthi Mohammed Abdulrahman , Lahiq Lama Ali , Al Fae Faisal Mohammed , Alwadie Awad Mohammed , Al-Qahtani Shuruq Abdullah , Al Amri Faisal Suhaim , Tobeigei Faisal Hassan
Published: September 2023

The overall risk of developing cancer before the age of 75 years in the Kingdom of Saudi Arabia is 9.9%. We aimed to explore the pattern of skin cancer, specifically among the Saudi population residing in the Aseer region. We obtained data from the medical records of Aseer Central Hospital regional histopathological laboratory considering surgical pathology reports from 2011 to 2021. The 61–80-year-old age group represented most of the cases (41.4%), followed by the 41–60-year-old group at 24.1%. Men made up the majority of the cases (59.4%). Furthermore, the dataset predominantly consisted of Saudi nationals (94.3% of the sample). The percentage of cases diagnosed each year relative to the cumulative number of skin cancer cases varied each year, ranging from 1.6% in 2011 to 11.6% in 2017. The most common diagnoses were squamous cell carcinoma (SCC) with 230 cases (41.1%) and basal cell carcinoma (BCC) with 147 cases (26.3%). The majority of cases occurred in the head and neck region (55.4%), followed by the lower limb (16.6%), trunk (13.6%), upper limb (8.2%), and pelvis (2.3%). There was a significant variation in the type of skin cancer across the age groups (p < 0.001) and across different body parts (p < 0.001). The incidence of skin cancer exhibited variability throughout the study period. The predominant diagnoses observed were SSC and BCC. Among the affected areas, the head and neck region displayed the highest prevalence, followed by the lower limb, trunk, upper limb, and pelvis.
Significance of 8-OHdG Expression as a Predictor of Survival in Colorectal Cancer
Authors: Kang Myunghee , Jeong Soyeon , Park Sungjin , Nam Seungyoon , Chung Jun-Won , Kim Kyoung Oh , An Jungsuk , Kim Jung Ho
Published: September 2023

The incidence of colorectal cancer (CRC) is increasing worldwide. 8-hydroxy-2′-deoxyguanosine (8-OHdG), one of the most prevalent DNA alterations, is known to be upregulated in several carcinomas; however, 8-OHdG has not been used to predict the prognosis of patients with CRC. We aimed to determine 8-OHdG levels in patients with CRC using immunohistochemistry and conducted a survival analysis according to the pathological stage. The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the low 8-OHdG subgroup were 1.41 (95% confidence interval (CI): 1.01–1.98, p = 0.04) and 1.60 (95% CI: 1.12–2.28, p = 0.01), respectively. When tumor node metastasis (TNM) staging and 8-OHdG expression were combined, the 5-year EFS and DSS HRs of patients with CRC with low 8-OHdG expression cancer at the same TNM stage (stage Ⅲ/Ⅳ) were 1.51 (95% CI: 1.02–2.22, p = 0.04) and 1.64 (95% CI: 1.09–2.48, p = 0.02), respectively, compared to those with high 8-OHdG expression cancer, indicating a poor prognosis. Therefore, low 8-OHdG expression is a significant predictive factor for 5-year EFS and DSS in patients with CRC, and it can serve as an essential biomarker of CRC.
Progerin, an Aberrant Spliced Form of Lamin A, Is a Potential Therapeutic Target for HGPS
Authors: Kim Bae-Hoon , Chung Yeon-Ho , Woo Tae-Gyun , Kang So-Mi , Park Soyoung , Park Bum-Joon
Published: September 2023

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder caused by the mutant protein progerin, which is expressed by the abnormal splicing of the LMNA gene. HGPS affects systemic levels, with the exception of cognition or brain development, in children, showing that cellular aging can occur in the short term. Studying progeria could be useful in unraveling the causes of human aging (as well as fatal age-related disorders). Elucidating the clear cause of HGPS or the development of a therapeutic medicine could improve the quality of life and extend the survival of patients. This review aimed to (i) briefly describe how progerin was discovered as the causative agent of HGPS, (ii) elucidate the puzzling observation of the absence of primary neurological disease in HGPS, (iii) present several studies showing the deleterious effects of progerin and the beneficial effects of its inhibition, and (iv) summarize research to develop a therapy for HGPS and introduce clinical trials for its treatment.
Electrochemical Perovskite-Based Sensors for the Detection of Relevant Biomarkers for Human Kidney Health
Authors: Piñón-Balderrama Claudia Ivone , Leyva-Porras César , Conejo-Dávila Alain Salvador , Estrada-Monje Anayansi , Maldonado-Orozco María Cristina , Reyes-López Simón Yobanny , Zaragoza-Contreras Erasto Armando
Published: September 2023

The importance of biomarker quantification in technology cannot be overstated. It has numerous applications in medical diagnostics, drug delivery, and the timely implementation of prevention and control strategies for highly prevalent diseases worldwide. However, the discovery of new tools for detection has become increasingly necessary. One promising avenue is the use of perovskite-based materials, which exhibit excellent catalytic activity and redox properties. These make them ideal candidates for the development of electrochemical sensors. In this review, the advances of purely non-enzymatic electrochemical detection of bio-analytes, with ABO3 perovskite form, are presented. The work allows the visualization of some of the modifications in the composition and crystal lattice of the perovskites and some variations in the assembly of the electrodes, which can result in systems with a better response to the detection of analytes of interest. These findings have significant implications for improving the accuracy and speed of biomarker detection, ultimately benefiting patients and healthcare professionals alike.
Arabic Patient-Reported Measures of Activity and Participation for Children: A Systematic Review of Psychometric Properties
Authors: Alghamdi Mohammed S. , Alharbi Enas , Alghamdi Rawan , Alhowimel Ahmed S. , Alenazi Aqeel M. , Alshehri Mohammed M. , Alqahtani Bader A. , Awali Abdulaziz
Published: September 2023

Aim: To systematically review measurement properties of Arabic patient-reported outcome measures (PROMs) that assess activity and participation in children with and without health conditions. Method: Four databases were searched. Arabic PROMs with focus on activity and/or participation constructs were selected. Data on measurement properties were extracted and the methodological quality of the studies was assessed by COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) risk of bias checklist. Result: Of the total 149 articles screened, only 10 studies involving 10 measures that assessed activity and/or participation in children with or without health conditions were included. The focus of all PROMs is primarily on the activity of daily living at home and/or school, but dimensions of measurement differed across PROMs. None of the PROMs demonstrated sufficient properties for all psychometrics. The most studied psychometric property was internal consistency, whereas the least studied psychometric property was structural validity. Responsiveness was not investigated in any of the studies included. Conclusions: Despite the presence of Arabic PROMs on activity and participation for children, none of the reviewed measures satisfied all psychometric properties. Clinicians and researchers are encouraged to carefully select PROMs that are psychometrically sound and appropriate for the construct being measured.
Microeconomics of Nitrogen Fertilization in Boreal Carbon Forestry
Authors: Kärenlampi Petri P.
Published: September 2023

The nitrogen fertilization of boreal forests is investigated in terms of microeconomics as a tool for carbon sequestration. The effects of nitrogen fertilization’s timing on the return rate on capital and the expected value of the timber stock are investigated within a set of semi-fertile, spruce-dominated boreal stands using an inventory-based growth model. Early fertilization tends to shorten rotations, reducing timber stock and carbon storage. The same applies to fertilization after the second thinning. Fertilization applied ten years before stand maturity is profitable and increases the timber stock, but the latter effect is small. The fertilization of mature stands, extending any rotation by ten years, effectively increases the carbon stock. Profitability varies but is increased by fertilization instead of merely extending the rotation.