bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Real-World Experience with Safinamide in Patients with Parkinson’s Disease
Authors: Planas-Ballvé Anna , Caballol Pons Núria , Peral Quirós Alejandro , Gómez Ruiz Isabel , Balagué Marmaña Marta , Velázquez Ballester Alexander J. , Lozano Moreno Dolors , Ávila Rivera Asunción
Published: December 2024

Introduction: Randomized clinical trials should be complemented with data from real-world studies. We report our long-term experience with safinamide in a movement disorders unit. Methods: This retrospective study included patients with Parkinson’s disease (PD) treated with safinamide in our unit from February 2016 to May 2022 under routine clinical practice. Assessments included the Hoehn and Yahr (HY) stage, unified Parkinson’s disease rating scale (UPDRS) part III score, levodopa equivalent daily dose (LEDD), LEDD for dopamine agonists, and safinamide treatment discontinuation. Results: We included 180 patients with a median age of 74 years (IQR 11), and the majority (90.6%) had an HY stage of ≤2. After a median follow-up of 40 months (IQR 34), 14 patients discontinued treatment with safinamide (7.8%, 95% CI 4.7 to 12.6). Among the 166 patients who remained on safinamide, the UPDRS III score was stable (10 (IQR 9) vs. 9 (IQR 13), p = 0.455). The LEDD significantly increased from a median of 300 mg to 500 mg (p < 0.001), whereas the LEDD for dopamine agonists did not significantly increase. A subgroup of 89 patients who did not require dopamine agonists during follow-up showed stable UPDRS III score (10 (IQR 7) vs. 9 (IQR 14); p = 0.923), with a significant LEDD increase (300 mg to 400 mg, p < 0.001). Conclusions: Our results support the long-term effectiveness and tolerability of safinamide in patients with PD in clinical practice.
“Walking with Dreams”: The Categories of Career Decision-Making Self-Efficacy and Its Influence on Learning Engagement of Senior High School Students
Authors: Liu Xuejun , Mei Xiongjie , Ji Guojun
Published: December 2024

Career decision-making self-efficacy is a key factor influencing high school students’ ability to make informed choices. It is closely associated with their professional interests, learning engagement, and academic performance. This study aims to explore the latent categories of career decision-making self-efficacy among Chinese high school students and analyze the differences in learning engagement across students with different types of career decision-making self-efficacy. A convenience sampling method was employed to recruit 510 Chinese high school students as participants. A questionnaire survey was conducted using the Career Decision-Making Self-Efficacy Scale and the Learning Engagement Scale. The validity of the questionnaire was analyzed using Amos 23.0, descriptive statistics and correlation analyses were performed with SPSS 26.0, and a latent profile model was constructed using Mplus 8.0. The results indicate that there are four latent categories of career decision-making self-efficacy among high school students. In terms of learning engagement levels, the categories are ranked from highest to lowest as follows: high career decision-making self-efficacy type, lack of external exploration type, lack of internal exploration type, and low career decision-making self-efficacy type. Students with high and low career decision-making self-efficacy demonstrated significantly higher levels of learning engagement compared to those categorized as lacking external or internal exploration. Therefore, the design of career education curricula for high school students should focus on enhancing career decision-making self-efficacy to stimulate their intrinsic motivation for learning. Differences among various student types should be acknowledged, allowing for tailored and individualized instruction. Additionally, efforts should be made to strengthen integrated career guidance that links academics, career interests, and future professions, guiding all stakeholders to shift away from entrenched practices of “exam-oriented education” and utilitarian perspectives.
A Meta-Analysis of the Effects of Interaction on Value Co-Creation in Online Collaborative Innovation Communities Based on the Service Ecosystem Framework
Authors: Wang Chunzhen , Zhao Xin , Hong Jianzhong
Published: December 2024

Interaction is typically at the core of the value co-creation process through operant resource exchange in online collaborative innovation communities (OCICs). While some studies emphasize the facilitating effect of interaction on value co-creation, others have drawn opposite conclusions, such as more peer interaction leads to less idea generation. Thus, the purpose of this paper is to utilize the service ecosystem framework to clarify the overall relationship between interaction and value co-creation and to explore the moderating factors that may have contributed to the divergence and inconsistency of previous studies. We conducted a meta-analysis of 65 effect sizes obtained from 63 articles with a cumulative sample size of 25,185 between 2004 and 2023, using a random effects model. The results indicate that interaction has a significantly positive impact on user value co-creation within OCICs (r = 0.453, 95%CI [0.405, 0.499]), and the heterogeneity among studies was significant (Q = 1409.29, p < 0.001). The strength of this correlation was moderated by the types of interaction (human–computer or human–human interactions), the types of OCICs (business-sponsored or socially constructed online communities), and the number of involved OCICs (one or multiple online communities), but not by the cultural background. These findings support the service ecosystem perspective rather than resource scarcity theory by resolving the mixed findings regarding the relationship between interaction and user value co-creation. Furthermore, this study systematically examined the contingent factors separately across three levels, micro (types of actor interactions), meso (types and number of OCICs), and macro (cultural background), combining the whole and the part insights, and empirically integrating service ecosystems as the foundational paradigm and unit of analysis for value co-creation research for the first time. This research contributes to theoretical frameworks in service ecosystems and offers actionable insights for management practices in business and marketing.
Simplified Procedure for Estimating Seismic Displacement Capacity of Concrete Piles in Wharves
Authors: Gao Shufei , Huang Zhenkun , Feng Yunfen
Published: December 2024

The procedure of estimating the seismic displacement capacity of piles under each performance level in current wharf practices involves monitoring the material strains specified in the design criteria during nonlinear static pushover analysis with a complex numerical model. Thus, a simplified procedure for concrete piles is proposed by developing closed-form formulas for displacement ductility capacity and yield displacement of piles, while the displacement capacity is the product of ductility capacity and yield displacement. The ductility capacity assures that the pile material strain limits specified in the criteria are not exceeded. The basic form of the formula for ductility capacity is established by using the equivalent cantilever concept to model the pile–soil interaction. Then, large quantities of moment–curvature analyses of sections and pushover analyses of concrete piles were conducted to determine the related parameters in the formula by considering numerous influencing factors. The results show that the ductility capacity can be expressed as a function of the curvature ductility capacity of pile sections at the selected performance level and parameter ψ. Based on the outcomes of curvature and pushover analyses, a set of practical formulas are proposed to determine the curvature ductility capacity, which depends on the longitudinal or transverse reinforcement ratios and axial force level, along with ψ, which depends on the aforementioned factors as well as the unsupported length of the pile.
Risk Assessment of Small-Diameter Shield Construction in a Deep Drainage Tunnel Based on an ISM–CRITIC–Cloud Model
Authors: Hu Kai , Wang Junwu , Wu Danhong , Wang Yingang
Published: December 2024

The deep drainage tunnel project is an important measure to alleviate urban waterlogging. The construction of a deep drainage tunnel is a complicated process, involving many influencing factors, and there are correlations among these influencing factors, so the risk assessment is difficult. In this study, the ISM method, CRITIC method and cloud model are combined to build a risk assessment model for the small-diameter shield construction of a deep drainage tunnel. Firstly, the risk index system of small-diameter shield construction in a deep drainage tunnel is put forward. Secondly, the ISM method is used to divide the risk indicators and extract the key risk factors. Then, these key risk factors are weighted with the CRITIC method, and the cloud model is used to evaluate the construction risk of a small-diameter shield of a deep drainage tunnel. Finally, the feasibility and accuracy of the proposed method are verified by a practical case. It was found that the risk assessment method proposed in this study can not only effectively assess the level of security risk, but also identify the key risk factors and rank the importance of these factors. The results of this study can reduce the interference items and workload of risk assessment to a certain extent, and help provide managers with an accurate decision-making basis.
Multi-Scale Network Analysis of Community-Based Senior Centers: Exploring the Intersection of Spatial Embeddedness and Accessibility in Nanjing, China
Authors: Xu Zhixin , Li Xiaoming
Published: December 2024

As critical infrastructure of age-friendly cities, senior centers are designed to be embedded in communities and facilitate service accessibility for older adults. However, their underutilization is widely documented, suggesting a need to reassess their effectiveness. Existing studies often analyze the issue focusing on socio-demographic factors, overlooking the spatial contexts in which senior centers are embedded and their impacts on older people’s access. This study aims to address the research gap by investigating the spatial embeddedness of senior centers using Space Syntax methods and examining its influence on older people’s access patterns. Using a geo-behavioral dataset collected in Nanjing, China, we find that about 70% of the senior centers in the research area are embedded in highly localized settings with limited connections to global street networks, which significantly restricts the access of older people from wider spatial contexts. This spatial segregation may force senior centers to incur higher costs to attract users, thereby reducing the effectiveness of community-based services. This study introduces a novel spatial perspective to evaluate community-based services, highlighting the critical influence of the spatial context on service accessibility. The findings provide valuable empirical insights for policymakers and planners striving to create age-friendly cities and communities.
Shear Elastic Buckling and Resistant Behavior of Single-Side-Stiffened Steel Corrugated Shear Walls
Authors: Zhang Rui-Ze , Wu Ruo-Min , Wang Ling-Qi , Fu Peng-Peng , Tong Jing-Zhong
Published: December 2024

Stiffened steel corrugated shear walls (SSCSWs) have achieved extensive applications in building structures and serve as efficient lateral force-resisting members. Single-side-stiffened steel corrugated shear walls (SS-SCSWs) are more flexible in terms of their structural configuration compared to conventional SSCSWs because this novel structural member effectively reduces wall thickness and simplifies the construction process. In this paper, numerical analyses were carried out to investigate the shear elastic buckling and resistant behavior of SS-SCSWs. A formula for the equivalent flexural stiffness of single-side stiffeners was given based on theoretical analysis. The elastic buckling and elastoplastic analyses of SS-SCSWs were carried out by finite element (FE) models to determine the value of the equivalent flexural stiffness coefficient. Meanwhile, the elastic and elastoplastic transition stiffness ratios of single-side stiffeners were proposed to predict the minimum stiffness required for the stiffener to provide sufficient constraint. The accuracy of the above formulas was verified by calculating the shear elastic buckling loads, the ultimate shear resistance, and the out-of-plane displacements of the SS-SCSWs. Furthermore, parametric analyses were performed to reveal the influences of the aspect ratio and plate thickness on shear resistance capacity. The equivalent flexural stiffness coefficients in both the elastic and elastoplastic analyses were determined to be 0.45 and 0.7, respectively, through curve fitting. The results indicated that the theory of BS-SCSWs could accurately predict the shear elastic and elastoplastic behavior of SS-SCSWs after modifying its expression for flexural stiffness. Consequently, the modified theoretical formulas were demonstrated to be suitable for SS-SCSWs in practical designs.
Study on the Stability of Unbalanced Rotation of Large-Tonnage T-Shaped Rigid Frame Bridges
Authors: Wu Hantao , Yang Zheng , Lu Chunting , Li Zhongming , Guo Chen , Sha Guohua
Published: December 2024

In the design of cantilever method bridge anti-overturning structures, the appropriate gap between the supporting foot and the lower rotating table is a crucial factor. It affects the distribution of the upper load and the friction force of the rotating structure, playing a key role in stability control. Currently, a reasonably defined range for this gap based on engineering practice has not been established. This study, set against the backdrop of practical engineering for large-tonnage rotational bridges, analyzes potential overturning instability forms during rotation. It provides a detailed examination of the stability performance of bridges in unbalanced states under single-side joint support configurations and analyzes the mechanical performance and stability under different gaps and impact velocities during rotation. The result is that the impact acceleration, angular acceleration of rotation, and tilt angle (gap) increase displacement and stress in the support system, posing a significant safety risk. The present research demonstrates the safety and rationality of the proposed unbalanced rotation and provides control limits for tilt angle and rotation acceleration during the rotation process. These results demonstrate that the proposed support mode ensures safety requirements during unbalanced rotation, offering insights for the design and construction of large-tonnage rotational bridges.
Evaluating YOLO Models for Efficient Crack Detection in Concrete Structures Using Transfer Learning
Authors: Sohaib Muhammad , Arif Muzamal , Kim Jong-Myon
Published: December 2024

The You Only Look Once (YOLO) network is considered highly suitable for real-time object detection tasks due to its characteristics, such as high speed, single-shot detection, global context awareness, scalability, and adaptability to real-world conditions. This work introduces a comprehensive analysis of various YOLO models for detecting cracks in concrete structures, aiming to assist in the selection of an optimal model for future detection and segmentation tasks. The YOLO models are initially trained on a dataset containing both images with and without cracks, producing a generalized model capable of extracting abstract features beneficial for crack detection. Subsequently, transfer learning is employed using a dataset that reflects real-world conditions, such as occlusions, varying crack sizes, and rotations, to further refine the model. Crack detection in concrete remains challenging due to the wide variation in crack sizes, aspect ratios, and complex backgrounds. To achieve optimal performance, we test different versions of YOLO, a state-of-the-art single-shot detector, and aim to balance inference speed and mean average precision (mAP). Our results indicate that YOLOv10 demonstrates superior performance, achieving a mean average precision (mAP) of 74.52% with an inference time of 19.5 milliseconds per image, making it the most effective among the models tested.
Generative Design Method for Single-Layer Spatial Grid Structural Joints
Authors: Liu Fengcheng , Xu Tao , Chan Yung (William Sasy)
Published: December 2024

Single-layer spatial grid joints are crucial to structural safety, with commonly used welded hollow spherical joints and cast steel joints. However, these traditional joints face limitations, including a rigid design, excessive weight, and susceptibility to stress concentration. As engineering practices advance, these joints struggle to meet modern requirements. This paper introduces a generative method for designing rigid joints in single-layer spatial grid structures, based on Audze space-filling criteria. The method’s mathematical formulation is presented, followed by developing novel joint configurations by exploring various cross-sectional forms, retention mass, and geometric elements, while considering bending moments. A comparative analysis of static properties between the new and traditional joints shows promising results. The generative approach demonstrates significant innovation, producing lightweight, aesthetically pleasing, and structurally efficient joints. Compared to conventional welded hollow spherical joints, the new joints exhibit a 57% reduction in self-weight, a 51% decrease in maximum equivalent stress, and a 24% reduction in maximum displacement. This method enables versatile and optimized joint design for single-layer spatial grid structures, offering enhanced strength, safety, and aesthetic appeal.
Beyond Obstruction: Evaluating Self-Expandable Metallic Stents (SEMSs) vs. Emergency Surgery for Challenging pT4 Obstructive Colon Cancer: Multicentre Retrospective Study
Authors: Paniagua García-Señoráns Marta , Cerdán-Santacruz Carlos , Cano-Valderrama Oscar , Aldrey-Cao Inés , Andrés-Asenjo Beatriz , Pereira-Pérez Fernando , Flor-Lorente Blas , Biondo Sebastiano ,   on Behalf of Collaborating Group for the Study of Metachronous Peritoneal Metastases of pT4 Colon Cancer
Published: December 2024

Background/Objectives: Colon cancer presents as an obstruction in almost 30% of patients. Self-expandable metallic stents emerged as an alternative to emergency surgery, despite early controversies around their use. Improved techniques led to stent incorporation in clinical guidelines. Our objective is to compare colectomies performed after the insertion of self-expandable metallic stents versus emergency surgeries in pT4 obstructive left colon cancer, analysing postoperative and oncological outcomes. Methods: This is an observational retrospective multicentre study involving 50 hospitals and analysing data from patients with pT4 obstructive tumours treated for curative intent between 2015 and 2017. Patients with left-sided obstructive colon cancer were included, with exclusion criteria being palliative surgery or incomplete resection. Primary outcomes were local, peritoneal, and systemic recurrence rates, overall survival (OS), and disease-free survival (DFS). Secondary outcomes were postoperative complications and the rate of surgeries without major complications. Results: In total, 196 patients were analysed, 128 undergoing emergency surgery and 68 receiving colonic stents. Stents more frequently allowed for minimally invasive surgeries: 33.8% vs. 4.7% (p < 0.01). The stent group showed fewer major complications (Clavien–Dindo ≥ 3) at 4.5% vs. 22.4% (p < 0.01), fewer infectious complications at 13.2% vs. 23.1% (p = 0.1), and fewer organ-space infections at 3.3% vs. 15.9% (p = 0.03). No significant differences in recurrence rates, 29.4% vs. 28.1% (p = 0.8); disease-free survival, 44.5 vs. 44.3 months (p = 0.5); or overall survival, 50.5 vs. 47.6 months (p = 0.4), were found between groups. Conclusions: Self-expandable metallic stents are a safe alternative for pT4 obstructive left colon cancer, improving postoperative outcomes without compromising short- and medium-term oncological results. Consideration of experienced clinicians and potential referral to centres with advanced stenting capabilities may enhance patient care.
Role of Imaging in Multiple Myeloma: A Potential Opportunity for Quantitative Imaging and Radiomics?
Authors: Michalska-Foryszewska Anna , Rogowska Aleksandra , Kwiatkowska-Miernik Agnieszka , Sklinda Katarzyna , Mruk Bartosz , Hus Iwona , Walecki Jerzy
Published: December 2024

Multiple myeloma (MM) is the second most prevalent hematologic malignancy, particularly affecting the elderly. The disease often begins with a premalignant phase known as monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma (SP) and smoldering multiple myeloma (SMM). Multiple imaging modalities are employed throughout the disease continuum to assess bone lesions, prevent complications, detect intra- and extramedullary disease, and evaluate the risk of neurological complications. The implementation of advanced imaging analysis techniques, including artificial intelligence (AI) and radiomics, holds great promise for enhancing our understanding of MM. The integration of advanced image analysis techniques which extract features from magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) images has the potential to enhance the diagnostic accuracy for MM. This innovative approach may lead to the identification of imaging biomarkers that can predict disease prognosis and treatment outcomes. Further research and standardized evaluations are needed to define the role of radiomics in everyday clinical practice for patients with MM.
Sex Disparities in Bladder Cancer Diagnosis and Treatment
Authors: Pignot Géraldine , Barthélémy Philippe , Borchiellini Delphine
Published: December 2024

Gender differences in prevalence, tumor invasiveness, response to treatment, and clinical outcomes exist in different types of cancer. The aim of this article is to summarize the sex disparities in bladder cancer diagnosis and treatment and try to suggest areas for improvement. Although men are at a higher risk of developing bladder tumors, women tend to be diagnosed with more advanced stages at diagnosis and are more likely to present with upfront muscle-invasive disease. Non-urothelial histological subtypes are more frequently reported in women. Regarding non-muscle-invasive bladder cancer (NMIBC), several studies have shown that women have a higher risk of disease recurrence after treatment with Bacillus Calmette–Guerin, due to different immunogenicities. In localized muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy and cystectomy are less likely to be performed on women and sexual-sparing procedures with neobladder diversion are rarely offered. Finally, women appear to have a poorer prognosis than men, potentially due to the sex-associated intrinsic features of hosts and tumors that may drive differential therapeutic responses, particularly to immune-based therapies. Women are also more likely to develop severe adverse events related to systemic therapies and are underrepresented in randomized studies, leading to a gap between the real world and trials. In conclusion, studies investigating the role of sex and gender are urgently needed to improve the management of urothelial carcinoma.
Bayesan Model to Predict R Status After Neoadjuvant Therapy in Pancreatic Cancer
Authors: Frigerio Isabella , Bao Quoc Riccardo , Bannone Elisa , Giardino Alessandro , Spolverato Gaya , Lorenzoni Giulia , Scopelliti Filippo , Girelli Roberto , Martignoni Guido , Regi Paolo , Azzolina Danila , Gregori Dario , Butturini Giovanni
Published: December 2024

Objective: To build a Bayesian approach-based model to predict the success of surgical exploration post-neoadjuvant treatment. Background: Pancreatic cancer (PDAC) is best treated with radical surgery and chemotherapy, offering the greatest chance of survival. Surgery after neoadjuvant treatment (NAT) is indicated in the absence of progression, knowing the limits in accurately predicting resectability with traditional radiology. R Status being a pathological parameter, it can be assessed only after surgery. Method: Patients successfully resected for histologically confirmed PDAC after NAT for BR and LA disease were included, with attention to the predictors of R status from the existing literature. The Bayesian logistic regression model was estimated for predicting the R1 status. The area under curve (AUC) of the average posterior probability of R1 was calculated and results were reported considering the 95% posterior credible intervals for the odds ratios, along with the probability of direction. Results: The final model demonstrated a commendable AUC value of 0.72, indicating good performance. The likelihood of positive margins was associated with older age, higher ASA score, the presence of venous and/or arterial involvement at preoperative radiology, tumor location within the pancreatic body, a lack of tumor size reduction post-NAT, and the persistence of an elevated Ca19.9 value. Conclusions: A Bayesian approach using only preoperative items is firstly used with good performance to predict R Status in pancreatic cancer patients who underwent resection after neoadjuvant therapy.
Aptamer’s Structure Optimization for Better Diagnosis and Treatment of Glial Tumors
Authors: Koshmanova Anastasia A. , Artyushenko Polina V. , Shchugoreva Irina A. , Fedotovskaya Victoriya D. , Luzan Natalia A. , Kolovskaya Olga S. , Zamay Galina S. , Lukyanenko Kirill A. , Veprintsev Dmitriy V. , Khilazheva Elena D. , Zamay Tatiana N. , Ivanova Daria A. , Kastyuk Maria R. , Lapin Ivan N. , Svetlichnyi Valery A. , Tomilin Felix N. , Shved Nikita A. , Gulaia Valeriia S. , Kumeiko Vadim V. , Berezovski Maxim V. , Kichkailo Anna S.
Published: December 2024

Background: Oncological diseases are a major focus in medicine, with millions diagnosed each year, leading researchers to seek new diagnostic and treatment methods. One promising avenue is the development of targeted therapies and rapid diagnostic tests using recognition molecules. The pharmaceutical industry is increasingly exploring nucleic acid-based therapeutics. However, producing long oligonucleotides, especially aptamers, poses significant production challenges. Objectives: This study aims to demonstrate the efficacy of using molecular modeling, supported by experimental procedures, for altering aptamer nucleotide sequences while maintaining their binding capabilities. The focus is on reducing production costs and enhancing binding dynamics by removing nonfunctional regions and minimizing nonspecific binding. Methods: A molecular modeling approach was employed to elucidate the structure of a DNA aptamer, Gli-55, facilitating the truncation of nonessential regions in the Gli-55 aptamer, which selectively binds to glioblastoma (GBM). This process aimed to produce a truncated aptamer, Gli-35, capable of forming similar structural elements to the original sequence with reduced nonspecific binding. The efficiency of the truncation was proved by flow cytometry, fluorescence polarization (FP), and confocal microscopy. Results: The molecular design indicated that the new truncated Gli-35 aptamer retained the structural integrity of Gli-55. In vitro studies showed that Gli-35 had a binding affinity comparable to the initial long aptamer while the selectivity increased. Gli-35 internalized inside the cell faster than Gli-55 and crossed the blood–brain barrier (BBB), as demonstrated in an in vitro model. Conclusions: The success of this truncation approach suggests its potential applicability in scenarios where molecular target information is limited. The study highlights a strategic and resource-efficient methodology for aptamer development. By employing molecular modeling and truncation, researchers can reduce production costs and avoid trial and error in sequence selection. This approach is promising for enhancing the efficiency of therapeutic agent development, particularly in cases lacking detailed molecular target insights.
Pancreatectomy with Celiac Axis Resection and Reconstruction for Locally Advanced Pancreatic Cancer
Authors: Mizutani Satoshi , Taniai Nobuhiko , Sukegawa Makoto , Haruna Takahiro , Furuki Hiroyasu , Takata Hideyuki , Ueda Junji , Yoshioka Masato , Aimoto Takayuki , Sakamoto Shunichiro , Suzuki Kenji , Nakamura Yoshiharu , Yoshida Hiroshi
Published: December 2024

Background: With the advent of effective chemotherapy, conversion surgery (CS) has been performed in patients who have responded to pretreatment, even for pancreatic cancer diagnosed as unresectable (UR) at the time of initial diagnosis. In CS, major arterial resection and reconstruction are necessary for complete radical resection. Methods: We discuss the key points for safely performing pancreatectomy with celiac axis (CA) resection combined with reconstruction, divided into resection and arterial reconstruction. The possibility of safe pancreatectomy concurrent with CA resection and reconstruction depends on the ability to create a “golden view” that provides an unimpaired view of the Abdominal Aorta, CA, Superior Mesenteric Artery, Inferior Vena Cava, and left renal vein from the ventral side. Pancreatectomy concurrent with CA resection requires arterial reconstruction. Postoperatively, arterial blood flow must be maintained. To achieve this, tension-free and short bypass should be observed. Results: From 2014 to 2024, sixteen URLA patients underwent CS, requiring major artery en bloc resection after pretreatment. We performed DP-CAR in eight patients, gastrectomy-distal pancreatectomy-splenectomy (Appleby procedure) procedure in one patient, PD-CHAR in two patients, PD-CAR in two patients, TP-CAR(spleen preserving) in one patient, and TP-CAR+TG in two patients. In total, five patients required surgery with CA reconstruction. Histopathologically, four of the five patients had T4 pancreatic cancer. The R0 surgical rate was 80%. Complication of Clavien–Dindo IIIa or higher was observed in one patient. There were no deaths. Conclusions: Parallel to the determination of pretreatment, surgeons must be prepared to safely and reliably perform pancreatectomies that require concurrent major arterial resection and reconstruction.
Prediagnostic Plasma Nutrimetabolomics and Prostate Cancer Risk: A Nested Case–Control Analysis Within the EPIC Study
Authors: Almanza-Aguilera Enrique , Martínez-Huélamo Miriam , López-Hernández Yamilé , Guiñón-Fort Daniel , Guadall Anna , Cruz Meryl , Perez-Cornago Aurora , Rostgaard-Hansen Agnetha L. , Tjønneland Anne , Dahm Christina C. , Katzke Verena , Schulze Matthias B. , Masala Giovanna , Agnoli Claudia , Tumino Rosario , Ricceri Fulvio , Lasheras Cristina , Crous-Bou Marta , Sánchez Maria-Jose , Aizpurua-Atxega Amaia , Guevara Marcela , Tsilidis Kostas K. , Chatziioannou Anastasia Chrysovalantou , Weiderpass Elisabete , Travis Ruth C. , Wishart David S. , Andrés-Lacueva Cristina , Zamora-Ros Raul
Published: December 2024

Background and Objective: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. Methods: We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations between metabolite concentrations and PCa risk were estimated by multivariate conditional logistic regression analysis. False discovery rate (FDR) was used to control for multiple testing correction. Results: Thirty-one metabolites (predominately derivatives of food intake and microbial metabolism) were associated with overall PCa risk and its clinical subtypes (p < 0.05), but none of the associations exceeded the FDR threshold. The strongest positive and negative associations were for dimethylglycine (OR = 2.13; 95% CI 1.16–3.91) with advanced PCa risk (n = 157) and indole-3-lactic acid (OR = 0.28; 95% CI 0.09–0.87) with fatal PCa risk (n = 57), respectively; however, these associations did not survive correction for multiple testing. Conclusions: The results from the current nutrimetabolomics study suggest that apart from early metabolic deregulations, some biomarkers of food intake might be related to PCa risk, especially advanced and fatal PCa. Further independent and larger studies are needed to validate our results.
Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders
Authors: Zhang Qi , Yim Rita , Lee Paul , Chin Lynn , Li Vivian , Gill Harinder
Published: December 2024

Clonal hematopoiesis (CH) is associated with an increased risk of developing myeloid neoplasms (MNs) such as myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). In general, CH comprises clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). It is an age-related phenomenon characterized by the presence of somatic mutations in hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells (HSPCs) that acquire a fitness advantage under selection pressure. Individuals with CHIP have an absolute risk of 0.5–1.0% per year for progressing to MDS or AML. Inflammation, smoking, cytotoxic therapy, and radiation can promote the process of clonal expansion and leukemic transformation. Of note, exposure to chemotherapy or radiation for patients with solid tumors or lymphomas can increase the risk of therapy-related MN. Beyond hematological malignancies, CH also serves as an independent risk factor for heart disease, stroke, chronic obstructive pulmonary disease, and chronic kidney disease. Prognostic models such as the CH risk score and MN-prediction models can provide a framework for risk stratification and clinical management of CHIP/CCUS and identify high-risk individuals who may benefit from close surveillance. For CH or related disorders, therapeutic strategies targeting specific CH-associated mutations and specific selection pressure may have a potential role in the future.
Contrastive Clustering-Based Patient Normalization to Improve Automated In Vivo Oral Cancer Diagnosis from Multispectral Autofluorescence Lifetime Images
Authors: Caughlin Kayla , Duran-Sierra Elvis , Cheng Shuna , Cuenca Rodrigo , Ahmed Beena , Ji Jim , Martinez Mathias , Al-Khalil Moustafa , Al-Enazi Hussain , Jo Javier A. , Busso Carlos
Published: December 2024

Background: Multispectral autofluorescence lifetime imaging systems have recently been developed to quickly and non-invasively assess tissue properties for applications in oral cancer diagnosis. As a non-traditional imaging modality, the autofluorescence signal collected from the system cannot be directly visually assessed by a clinician and a model is needed to generate a diagnosis for each image. However, training a deep learning model from scratch on small multispectral autofluorescence datasets can fail due to inter-patient variability, poor initialization, and overfitting. Methods: We propose a contrastive-based pre-training approach that teaches the network to perform patient normalization without requiring a direct comparison to a reference sample. We then use the contrastive pre-trained encoder as a favorable initialization for classification. To train the classifiers, we efficiently use available data and reduce overfitting through a multitask framework with margin delineation and cancer diagnosis tasks. We evaluate the model over 67 patients using 10-fold cross-validation and evaluate significance using paired, one-tailed t-tests. Results: The proposed approach achieves a sensitivity of 82.08% and specificity of 75.92% on the cancer diagnosis task with a sensitivity of 91.83% and specificity of 79.31% for margin delineation as an auxiliary task. In comparison to existing approaches, our method significantly outperforms a support vector machine (SVM) implemented with either sequential feature selection (SFS) (p = 0.0261) or L1 loss (p = 0.0452) when considering the average of sensitivity and specificity. Specifically, the proposed approach increases performance by 2.75% compared to the L1 model and 4.87% compared to the SFS model. In addition, there is a significant increase in specificity of 8.34% compared to the baseline autoencoder model (p = 0.0070). Conclusions: Our method effectively trains deep learning models for small data applications when existing, large pre-trained models are not suitable for fine-tuning. While we designed the network for a specific imaging modality, we report the development process so that the insights gained can be applied to address similar challenges in other non-traditional imaging modalities. A key contribution of this paper is a neural network framework for multi-spectral fluorescence lifetime-based tissue discrimination that performs patient normalization without requiring a reference (healthy) sample from each patient at test time.
Lack of Prophylactic Cranial Irradiation for Extensive Small-Cell Lung Cancer in Real Life, with the Emergence of Immunotherapy
Authors: Daumas Alice , Bigarre Celestin , Boucekine Mohamed , Zaccariotto Audrey , Kaeppelin Bertrand , Mogenet Alice , Gouton Etienne , Pluvy Johan , Tomasini Pascale , Muracciole Xavier , Benzekry Sebastien , Greillier Laurent , Padovani Laetitia
Published: December 2024

Background: Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, the introduction of immunotherapy in the management of the disease has raised new questions, and there is a lack of data on PCI and immunotherapy. We report a single-center retrospective study evaluating the impact of omitting PCI from real-life treatment, including immunotherapy, of patients with ES-SCLC. Methods: We identified patients followed at APHM between January 2014 and January 2021 for ES-SCLC without BM with an indication for PCI. The main assessment criteria considered in this study were overall survival (OS) and brain metastasis-free survival (BMFS) between patients who received PCI and those who did not. Results: 56 patients were included, 25 receiving PCI and 31 without PCI. The median follow-up was 16 months. Eighteen patients received immunotherapy, mostly in the group without PCI (p = 0.024). The median OS and BMFS were, respectively, 11.7 and 13.4 months in patients with PCI, and 20.3 and 10.7 months in patients without PCI, without any significant statistical difference (p = 0.412, p = 0.336). The prognostic factors highlighted in multivariate analysis were initial performance status (PS) < 2 for OS (HR = 2.74 (IC95% [1.23; 6.13])) and monocyte lymphocyte ratio (MLR) < 0.12 for BMFS (HR = 1.21 (IC95% [1.01; 1.45])). A recursive partitioning analysis (RPA) found PS, immunotherapy, and age to be influential factors for OS but not PCI. Conclusions: The clinical results of our study showed no benefit of PCI in terms of OS and BMFS for patients with ES-SCLC. This can be explained by the lack of benefit of PCI or by the introduction of immunotherapy.
Green and Eco-Friendly Egg White–TiO2 Hydrogel with Enhanced Antimicrobial, Adsorptive, and Photocatalytic Properties
Authors: Zhang Mei , Wang Xu
Published: December 2024

The design of multi-purpose decontaminants with environmentally friendly characteristics, low cost, and high efficiency in removing pollutants from the environment is an effective and economic strategy for maintaining the long-term development of the ecosystem. Based on the strategy of killing two birds with one stone, an egg white (EW)/TiO2 hydrogel with a porous structure is devised as a bio-adsorbent using waste eggs nearing their expiration date for simultaneously achieving the efficient removal of organic dyes and the inactivation of microorganisms from industrial wastewater. The characterizations of its morphology and composition using scanning electron microscopy (SEM), the Brunauer–Emmett–Teller (BET) theory, energy-dispersive spectrometry (EDS), Fourier transform infrared spectroscopy (FTIR), and a thermogravimetric analyzer (TGA) validate the successful synthesis of EW/TiO2. The maximum adsorption capacity of EW/TiO2 is 333.172 mg∙mL−1 according to the Langmuir model. The photodegradation of a methyl blue (MB) solution under irradiation via a xenon lamp is used to assess the photocatalytic behavior of EW/TiO2. Among the different samples, the 5 wt% TiO2-doped EW/TiO2 hydrogel shows an efficiency of 99% for 120 min of irradiation. Finally, the antibacterial properties of the EW/TiO2 hydrogel are evaluated by calculating its bacterial survival rate against Escherichia coli (E. coli). The EW/TiO2 photocatalyst exhibits a photocatalytic inactivation efficiency of 90.4%, indicating that the EW/TiO2 hydrogel possesses positive antibacterial activity via effectively inhibiting the growth of the bacteria, which is suitable for industrial wastewater treatment over a long period of time.
UV-Activated and Fe2+-Catalyzed H2O2 for the Treatment of Dye-Contaminated Water: Kinetics, Mechanism and Toxicity Investigations
Authors: Ahmad Wisal , Shah Roman , Haq Hameed Ul , Khan Dilaram , Khan Shahab , Al-Anazi Abdulaziz , Khan Javed Ali , Binte Razzak Nusrat Rezwana , Han Changseok
Published: December 2024

This study investigated the removal of methylene blue (MB) by different UV, UV-catalyzed H2O2 (UV/H2O2) and UV-and-iron-catalyzed H2O2 (UV/H2O2/Fe2+)-based advanced oxidation processes. At pH 6.0, the removal of MB (15 mg/L) was found to be 6.31% at 60 min for UV only. However, the combination of H2O2 (5 mM) with UV greatly enhanced the removal efficiency as 96.44% degradation of MB was found in the UV/H2O2 process at 60 min. Furthermore, the UV/H2O2/Fe2+ process was observed to be even more efficient than UV/H2O2, achieving 99.11% MB degradation at 30 min of treatment under the experimental conditions of [MB]0 = 15 mg/L, [H2O2]0 = 2 mM, [Fe2+]0 = 0.5 mg/L, and pH0 = 3.0. Furthermore, the removal of TOC was found to be 59 and 71% for UV/H2O2 and UV/H2O2/Fe2+, respectively. The pH did not change the efficiency of the UV/H2O2 process significantly; however, it greatly affected the efficiency of the UV/H2O2/Fe2+ system. The results demonstrate that both UV/H2O2 and UV/H2O2/Fe2+ could be used for the effective degradation and mineralization of MB.
LINC01270 Regulates the NF-κB-Mediated Pro-Inflammatory Response via the miR-326/LDOC1 Axis in THP-1 Cells
Authors: Arab Imene , Lim Su-Geun , Suk Kyoungho , Lee Won-Ha
Published: December 2024

Long intergenic noncoding (LINC)01270 is a 2278 bp transcript belonging to the intergenic subset of long noncoding (lnc)RNAs. Despite increased reports of LINC01270’s involvement in different diseases, evident research on its effects on inflammation is yet to be achieved. In the present study, we investigated the potential role of LINC01270 in modulating the inflammatory response in the human monocytic leukemia cell line THP-1. Lipopolysaccharide treatment upregulated LINC01270 expression, and siRNA-mediated suppression of LINC01270 enhanced NF-κB activity and the subsequent production of cytokines IL-6, IL-8, and MCP-1. Interestingly, the knockdown of LINC01270 downregulated expression of leucine zipper downregulated in cancer 1 (LDOC1), a novel NF-κB suppressor. An analysis of the LINC01270/micro-RNA (miRNA)/protein interactome profile identified miR-326 as a possible mediator. Synthetic RNA agents that perturb the interaction among LINC01270, miR-326, and LDOC1 mRNA mitigated the changes caused by LINC01270 knockdown in THP-1 cells. Additionally, a luciferase reporter assay in HEK293 cells further confirmed that LINC01270 knockdown enhances NF-κB activation, while its overexpression has the opposite effect. This study provides insight into LINC01270’s role in modulating inflammatory responses to lipopolysaccharide stimulation in THP-1 cells via the miR-326/LDOC1 axis, which negatively regulates NF-κB activation.
Extract of Curculigo capitulata Ameliorates Postmenopausal Osteoporosis by Promoting Osteoblast Proliferation and Differentiation
Authors: Wang Ying , Wang Xueru , Wang Kaijin , Qin Weiwei , Li Ning
Published: December 2024

Postmenopausal osteoporosis (PMOP) is a bone disease characterized by bone thinning and an increased risk of fractures due to estrogen deficiency. Current PMOP therapies often result in adverse side effects. The traditional medicinal plant Curculigo capitulata is commonly used to strengthen bones and support kidney function, but its role in treating PMOP is not well understood. This study aims to investigate the therapeutic effects of the total extract of Curculigo capitulata (Eocc) on PMOP and to explore the underlying mechanisms. The major components of the extract were identified using HPLC. Transcriptomics was employed to predict potential targets. An osteogenic differentiation model of MC3T3-E1 cells was used in vitro. The osteogenic potential of the Eocc was assessed through CCK-8 cell viability assays, alkaline phosphatase (ALP) staining, Alizarin Red staining, Western blotting, and qPCR. MCF-7 and HEK-293 cells were utilized to evaluate the estrogen-like activity of Eocc. Apoptosis rates were detected by flow cytometry. In vivo, a bilateral ovariectomized mouse model of PMOP was used to further validate the in vitro findings through histopathological analysis and WB results. The results demonstrated that the Eocc promoted the proliferation of MC3T3-E1 cells, increased ALP activity, and stimulated the formation of osteogenic mineralized nodules. It also upregulated the expression of osteogenic markers (Runx2, OCN, OPN, and BSP) at both the protein and mRNA levels. The Eocc induced the activation of ERα both in vitro and in vivo, initiating the Src/PI3K/AKT signaling pathway, leading to the phosphorylation of GSK3β and subsequent osteogenesis. The activation of this pathway also stimulated the phosphorylation of mTOR and p70S6K while downregulating cleaved caspase-3 and caspase-9. Additionally, the Eocc reduced apoptosis during osteogenic differentiation and promoted cell proliferation. These findings suggest that the Eocc facilitates osteoblast proliferation and differentiation, improving bone integrity in PMOP mice, and may represent a promising therapeutic candidate for managing PMOP.
Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index
Authors: Kim Sukyung , Rahim Md Abdur , Tajdozian Hanieh , Barman Indrajeet , Park Hyun-A , Yoon Youjin , Jo Sujin , Lee Soyeon , Shuvo Md Sarower Hossen , Bae Sung Hae , Lee Hyunji , Ju Sehee , Park Chae-eun , Kim Ho-Kyoung , Han Jeung Hi , Kim Ji-Woong , Yoon Sung geon , Kim Jae Hong , Choi Yang Gyu , Lee Saebim , Seo Hoonhee , Song Ho-Yeon
Published: December 2024

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.