bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Machine Learning Models Through PCA, SMOTE-ENN, and Stochastic Weighted Averaging
Authors: Han Youngjin , Joe Inwhee
Published: October 2024

Predicting survival outcomes in critical accidents has been a focal point in machine learning research. This study addresses several limitations of existing methods, including insufficient management of data imbalance, lack of emphasis on hyperparameter tuning, and proneness to overfitting. Many existing models struggle to generalize effectively on imbalanced datasets or depend on default hyperparameter settings, resulting in biased predictions. By integrating Principal Component Analysis (PCA), hyperparameter optimization, and resampling methods, as well as combining Edited Nearest Neighbors (ENN) with the Synthetic Minority Oversampling Technique (SMOTE), the model significantly improves predictive accuracy and model generalization. An ensemble model combining seven machine learning algorithms—Logistic Regression, Support Vector Machine, KNN, Random Forest, XGBoost, LightGBM, and CatBoost—was applied to predict survival outcomes. Stochastic Weighted Averaging (SWA) was applied to mitigate overfitting and enhance generalization. The accuracy increased from 91.97% to 94.89% after SWA was applied in this specific scenario. The combination of PCA-based dimensionality reduction, hyperparameter tuning, and resampling techniques (ENN + SMOTE) ensured the model handled data imbalance and optimized predictive accuracy. The final model demonstrated excellent performance, with Area Under the Curve (AUC) and Average Precision (AP) values both reaching 0.98, indicating high accuracy and precision. These improvements were validated using the Titanic dataset in a binary classification problem of predicting passenger survival. The results emphasize that ensemble learning, enhanced by SWA, offers a powerful framework for handling imbalanced and complex datasets, providing significant advancements in predictive modeling accuracy. This study provides insights into how machine learning techniques can be effectively combined to solve classification challenges in real-world scenarios.
Crack Growth Analysis of a Welded Centre Sill in a Hopper Wagon
Authors: Peng Daren , Jones Rhys , Ang Andrew S. M.
Published: October 2024

This paper mainly studies the fatigue cracks growth of fillet weld specimens in a fashion that is consistent with that used to assess the fatigue performance of complex aerospace structures under operational flight loads. The fatigue test loads were determined using the overall finite element analysis results of the hopper wagon. The actual applied test loads were monitored using strain gauges. The residual stress in the critical region was determined by combining the stress field of the welded specimen obtained by a thermal imager under cyclic loading with the results of the three-dimensional finite element analysis of the specimen. During the fatigue test, a digital camera (with microscope lens) was used in conjunction with infrared measurement technology to obtain the crack growth information. As in prior studies, the three dimensional finite element alternating technique was used to calculate the stress intensity factor in the critical area of the crack in the fillet weld specimen. The Hartman–Schijve crack growth equation was then used, in conjunction with the calculated stress intensity factor solutions, to compute the crack growth history in a fatigue test of a critical welded component in a hopper wagon. The resultant computed crack growth histories are relatively consistent with the test results.
Climate Change Mitigation and Adaptation in Ghana: Strategies and Challenges Faced by Social Enterprises
Authors: Ahatsi Emmanuel , Nie Lin , Olanrewaju Oludolapo Akanni
Published: October 2024

This research examined how social enterprises mitigate and adapt to climate change in Ghana, examining their strategies and challenges. The study adopted a descriptive research design and involved 379 social enterprises. Questionnaires were administered online, and data were analysed using descriptive statistics and a mean value ranking analysis. The findings revealed that the key strategies employed in climate change mitigation and adaptation include creating new funding models, promoting sustainable agriculture and food systems, forming strategic partnerships and networks, and implementing community-based renewable energy systems. The significant challenges in addressing climate change include competition from large organisations, cultural perspectives towards climate change, policy volatility, and lack of adequate technical skills. Hence, the study recommends developing specialised funding programmes for climate-focused social enterprises, climate change education and awareness campaigns, and capacity building to upgrade technical competencies in clean technologies and climate resilience design.
Assessment of the Drought Risk in Constanta County, Romania
Authors: Maftei Carmen Elena , Bărbulescu Alina , Osman Amela
Published: October 2024

Drought poses a significant risk in many parts of the world, especially in regions reliant on agriculture. Evaluating this risk is an essential step in preventing and reducing its impact. In this context, we assess the drought intensity at six sites in Constanța County (Romania) using the de Martonne aridity index. The risk of aridity and vulnerability to drought were evaluated by the Drought Hazard Index (DHI) and Drought Risk Index (DRI), computed based on the Standardized Precipitation Index (SPI). The de Martonne index indicates a variation between the slightly arid and semi-arid climates for Adamclisi station, with periodic changes from semi-arid to arid. At Cernavodă station, we notice a passage from an arid period towards a moderately humid one (in 2005), followed by a movement in the opposite direction to the limit of the arid zone (in 2011), and a return inside the “limits” of the semi-arid to moderately arid climate. A similar variation for 2000–2018 is noticed at Medgidia, Hârșova, and Mangalia. DRI classifies two stations in the low risk to drought category and one in the moderate risk to drought class. The other two locations experience a high or very high risk of drought. The drought intensities varied in the intervals 0.503–1.109 at Constanța, 0.473–1.363 at Mangalia, 0.511–1.493 at Adamclisi, 0.438–1.602 at Hârșova, 0.307–1.687 at Medgidia, and 0.463–1.307 at Cernavodă, and the prolonged drought periods were over 99 months at all stations.
Enhanced Diabetes Detection and Blood Glucose Prediction Using TinyML-Integrated E-Nose and Breath Analysis: A Novel Approach Combining Synthetic and Real-World Data
Authors: Gudiño-Ochoa Alberto , García-Rodríguez Julio Alberto , Cuevas-Chávez Jorge Ivan , Ochoa-Ornelas Raquel , Navarrete-Guzmán Antonio , Vidrios-Serrano Carlos , Sánchez-Arias Daniel Alejandro
Published: October 2024

Diabetes mellitus, a chronic condition affecting millions worldwide, necessitates continuous monitoring of blood glucose level (BGL). The increasing prevalence of diabetes has driven the development of non-invasive methods, such as electronic noses (e-noses), for analyzing exhaled breath and detecting biomarkers in volatile organic compounds (VOCs). Effective machine learning models require extensive patient data to ensure accurate BGL predictions, but previous studies have been limited by small sample sizes. This study addresses this limitation by employing conditional generative adversarial networks (CTGAN) to generate synthetic data from real-world tests involving 29 healthy and 29 diabetic participants, resulting in over 14,000 new synthetic samples. These data were used to validate machine learning models for diabetes detection and BGL prediction, integrated into a Tiny Machine Learning (TinyML) e-nose system for real-time analysis. The proposed models achieved an 86% accuracy in BGL identification using LightGBM (Light Gradient Boosting Machine) and a 94.14% accuracy in diabetes detection using Random Forest. These results demonstrate the efficacy of enhancing machine learning models with both real and synthetic data, particularly in non-invasive systems integrating e-noses with TinyML. This study signifies a major advancement in non-invasive diabetes monitoring, underscoring the transformative potential of TinyML-powered e-nose systems in healthcare applications.
Regenerative Outcomes of Combining siCOL1A2 Hydrogel with Acupuncture in a Rat Model of Chronic Intervertebral Disc Degeneration
Authors: Zhang Qianfu , Li Zhixuan , Zhou Sihan , Li Ji
Published: October 2024

Intervertebral disc degeneration (IVDD) is a significant cause of chronic pain and disability, necessitating innovative therapeutic strategies. This study investigates the combined effect of a novel siCOL1A2-encapsulated hydrogel and acupuncture on IVDD in a rat model. We developed a hydrogel system, siCOL1A2-encapsulated G5-PBA hydrogel (siCOL1A2@G5-PBA@Gel), designed for sustained siRNA delivery to the degenerated discs and assessed its therapeutic efficacy alongside acupuncture treatment. Key inflammatory genes were identified through RNA-seq analysis, with COL1A2 highlighted as a crucial regulator of inflammatory responses in IVDD. Our in vivo experiments involved treating rats with hydrogel alone, acupuncture alone, and combining both. The treatments were evaluated through behavioral pain assessments, imaging techniques (X-ray and MRI), and histological analyses. Results indicated that the combination therapy significantly alleviated pain, reduced inflammation, and promoted disc regeneration more effectively than individual treatments. The hydrogel proved biocompatible and facilitated targeted gene silencing, while acupuncture enhanced therapeutic outcomes by improving local blood circulation and modulating inflammatory responses. These findings suggest that integrating siCOL1A2 hydrogel with acupuncture offers a promising approach to treating IVDD.
Investigating the Role of Hub Calcification Proteins in Atherosclerosis via Integrated Transcriptomics and Network-Based Approach
Authors: Alharbi Hajed Obaid A. , Khan Asifa , Rahmani Arshad Husain
Published: October 2024

Atherosclerosis (AS) is a chronic inflammatory condition of the arteries, characterized by plaque formation that can restrict blood flow and lead to potentially fatal cardiovascular events. Given that AS is responsible for a quarter of global deaths, this study aimed to develop a systematic bioinformatics approach to identify biomarkers and regulatory targets involved in plaque development, with the goal of reducing cardiovascular disease risk. AS-specific mRNA expression profiles were retrieved from a publicly accessible database, followed by differentially expressed genes (DEGs) identification and AS-specific weighted gene co-expression network (WGCN) construction. Thereafter, calcification and atherosclerosis-specific (CASS) DEGs were utilized for protein–protein interaction network (PPIN) formation, followed by gene ontology (GO) term and pathway enrichment analyses. Lastly, AS-specific 3-node miRNA feed-forward loop (FFL) construction and analysis was performed. Microarray datasets GSE43292 and GSE28829 were obtained from gene expression omnibus (GEO). A total of 3785 and 6176 DEGs were obtained in case of GSE28829 and GSE43292; 3256 and 5962 module DEGs corresponding to GSE28829 and GSE43292 were obtained from WGCN. From a total of 54 vascular calcification (VC) genes, 20 and 29 CASS-DEGs corresponding to GSE28829 and GSE43292 were overlapped. As observed from FFL centrality measures, the highest-order subnetwork motif comprised one TF (SOX7), one miRNA (miR-484), and one mRNA (SPARC) in the case of GSE28829. Also, in the case of GSE43292, the highest-order subnetwork motif comprised one TF (ESR2), one miRNA (miR-214-3p), and one mRNA (MEF2C). These findings have important implications for developing new therapeutic strategies for AS. The identified TFs and miRNAs may serve as potential therapeutic targets for treating atherosclerotic plaques, offering insights into the molecular mechanisms underlying the pathogenesis and highlighting new avenues for research and treatment.
Selected Trace Elements and Their Impact on Redox Homeostasis in Eye Health
Authors: Wróblewska Joanna , Nuszkiewicz Jarosław , Wróblewski Marcin , Wróblewska Weronika , Woźniak Alina
Published: October 2024

Oxidative stress plays a crucial role in the pathogenesis of various ocular degenerative diseases, leading to structural and functional changes in eye tissues. This imbalance between reactive oxygen species (ROS) and antioxidants significantly contributes to conditions such as age-related macular degeneration, diabetic retinopathy, cataracts, and glaucoma. Both enzymatic and nonenzymatic antioxidants are vital for maintaining ocular health by neutralizing ROS and restoring cellular redox balance. Essential trace elements, including iron, zinc, copper, and selenium, are fundamental for the proper functioning of these antioxidant systems. Iron is indispensable for enzymatic activity and cellular energy production, zinc supports numerous proteins involved in visual functions and antioxidant defense, copper is essential for various enzymatic reactions preventing oxidative stress, and selenium is critical for the activity of antioxidant enzymes such as glutathione peroxidase (GPX) and thioredoxin reductase (TrxR). This review summarizes current research on the complex interactions between oxidative stress and trace elements in ocular diseases, highlighting the therapeutic potential of antioxidant supplementation to mitigate oxidative damage and improve eye health. By integrating insights from studies on oxidative stress, trace elements, and eye physiology, this article underscores new diagnostic and therapeutic strategies that could lead to more effective prevention and treatment of ocular diseases, aiming to enhance clinical outcomes and guide future research in optimizing therapeutic strategies for eye health.
Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches
Authors: Ucci Argia , Giacchi Luca , Rucci Nadia
Published: October 2024

Bone is the preferential site of metastasis for the most common tumors, including breast cancer. On the other hand, osteosarcoma is the primary bone cancer that most commonly occurs and causes bone cancer-related deaths in children. Several treatment strategies have been developed so far, with little or no efficacy for patient survival and with the development of side effects. Therefore, there is an urgent need to develop more effective therapies for bone primary tumors and bone metastatic disease. This almost necessarily requires the use of in vivo animal models that better mimic human pathology and at the same time follow the ethical principles for the humane use of animal testing. In this review we aim to illustrate the main and more suitable in vivo strategies employed to model bone metastases and osteosarcoma. We will also take a look at the recent technologies implemented for a partial replacement of animal testing.
Exploring the Antidiabetic and Antihypertensive Potential of Peptides Derived from Bitter Melon Seed Hydrolysate
Authors: Hung Wei-Ting , Sutopo Christoper Caesar Yudho , Mahatmanto Tunjung , Wu Mei-Li , Hsu Jue-Liang
Published: October 2024

Background/Objectives: Type 2 diabetes (T2D) has become a critical global health issue, with an increasing prevalence that contributes to significant morbidity and mortality. Inhibiting dipeptidyl peptidase-IV (DPP4) is a promising strategy for managing T2D. This study aimed to explore the DPP4 inhibitory peptide derived from bitter melon seed protein (BMSP) hydrolysate. Methods: Reversed-phase high-performance liquid chromatography (RP-HPLC) was utilized to fractionate the hydrolysate. Peptide in the highest activity fraction was analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Peptide synthetic was used for further characterizations, such as bioactivity exploration, inhibition mechanism, molecular docking, and peptide stability against in vitro simulated gastrointestinal (SGI) digestion. Results: The BMSP hydrolysate was digested with gastrointestinal proteases (GP) and assessed for DPP4 inhibitory activity, yielding an IC50 of 1448 ± 105 μg/mL. Following RP-HPLC fractionation, MPHW (MW4) and VPSGAPF (VF7) were identified from fraction F8 with DPP4 IC50 values of 128.0 ± 1.3 µM and 150.6 ± 3.4 µM, respectively. Additionally, MW4 exhibited potential antihypertensive effects through ACE inhibition with an IC50 of 172.2 ± 10.6 µM. The inhibitory kinetics and molecular docking simulations indicated that both MW4 and VF7 were competitive inhibitors of DPP4, while MW4 was also a competitive inhibitor of ACE. Importantly, both peptides remained stable during simulated gastrointestinal digestion, suggesting their resistance to human digestive processes and their capacity to maintain biological activity. Conclusions: The findings suggest that BMSP-GP hydrolysate may have potential in terms of the development of health foods or therapeutic agents. However, in vivo studies are also essential for further confirmation of efficacy.
Cellular Characteristics and Protein Signatures of Human Adipose Tissues from Donors With or Without Advanced Coronary Artery Disease
Authors: Ellis Caitlin P. S. , Tero Benjamin W. , Potts Christian M. , Malka Kimberly T. , Yang Xuehui , Hamilton Joshua , Vary Calvin , Khalil Andre , Liaw Lucy
Published: October 2024

Background/Objectives: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. Methods: We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease. Clinical and tissue pathologies and proteomics from adipose tissue were assessed. Results: Donors undergoing VR had a lower body mass index (p = 0.01), HbA1C (p = 0.0023), and incidence of diabetes (p = 0.022) compared to CABG. VR donors were overall healthier, with higher cardiac function compared to CABG donors, based on ejection fraction. Although adipose histopathology between groups was not markedly different, PVAT had smaller and more adipocytes compared to subcutaneous adipose tissues. These differences were validated by whole specimen automated morphological analysis, and anisotropy analysis showed small (2.8–7.5 μm) and large (22.8–64.4 μm) scale differences between perivascular and subcutaneous adipose tissue from CABG donors, and small scale changes (2.8–7.5 μm) between perivascular and subcutaneous adipose tissue from VR donors. Distinct protein signatures in PVAT and subcutaneous adipose tissue include those involved in secretion, exosomes and vesicles, insulin resistance, and adipocyte identity. Comparing PVAT and subcutaneous adipose tissue from CABG donors, there were 82 significantly different proteins identified with log fold change ≥ 0.3 or ≤−0.3 (p < 0.05). Using this threshold, there were 36 differences when comparing PVAT and subcutaneous adipose tissue from VR donors, 58 differences when comparing PVAT from CABG or VR donors, and 55 when comparing subcutaneous adipose tissue from CABG vs. VR donors. Conclusions: Routine histopathology cannot differentiate between PVAT from donors with or without coronary artery disease, but multiscale anisotropy analysis discriminated between these populations. Our mass spectrometry analysis identified a cohort of proteins that distinguish between adipose depots, and are also associated with the presence or absence of coronary artery disease.
Impact of Experimentally Induced Pain on Logical Reasoning and Underlying Attention-Related Psychophysiological Mechanisms
Authors: Gubler Danièle Anne , Zubler Rahel Lea , Troche Stefan Johannes
Published: October 2024

Background. Pain is known to negatively impact attention, but its influence on more complex cognitive abilities, such as logical reasoning, remains inconsistent. This may be due to compensatory mechanisms (e.g., investing additional resources), which might not be detectable at the behavioral level but can be observed through psychophysiological measures. In this study, we investigated whether experimentally induced pain affects logical reasoning and underlying attentional mechanisms, using both behavioral and electroencephalographic (EEG) measures. Methods. A total of 98 female participants were divided into a pain-free control group (N = 47) and a pain group (N = 51). Both groups completed the Advanced Progressive Matrices (APM) task, with EEG recordings capturing task-related power (TRP) changes in the upper alpha frequency band (10–12 Hz). We used a mixed design where all participants completed half of the APM task in a pain-free state (control condition); the second half was completed under pain induction by the pain group but not the pain-free group (experimental condition). Results. Logical reasoning performance, as measured by APM scores and response times, declined during the experimental condition, compared to the control condition for both groups, indicating that the second part of the APM was more difficult than the first part. However, no significant differences were found between the pain and pain-free groups, suggesting that pain did not impair cognitive performance at the behavioral level. In contrast, EEG measures revealed significant differences in upper alpha band power, particularly at fronto-central sites. In the pain group, the decrease in TRP during the experimental condition was significantly smaller compared to both the control condition and the pain-free group. Conclusions. Pain did not impair task performance at the behavioral level but reduced attentional resources, as reflected by changes in upper alpha band activity. This underscores the importance of incorporating more sensitive psychophysiological measures alongside behavioral measures to better understand the impact of pain on cognitive processes.
A PLS-SEM Analysis of Emotional Intelligence and Construction Organisation’s Performance Nexus in South Africa
Authors: Aghimien Lerato Millicent , Aigbavboa Clinton
Published: October 2024

Previous research has highlighted the critical role of emotional intelligence (EI) in enhancing employee performance. However, there is a notable gap in studies examining the connection between EI competencies and the performance of construction organisations, employees and overall project outcomes within the South African construction sector. This study analysed the relationship between EI and the performance of construction organisations to enhance project delivery through effective EI management among construction teams. A mixed-method approach was employed, utilising both Delphi techniques and a questionnaire survey. Data collected from construction experts were analysed using various statistical methods, including mean score, the Kruskal–Wallis H-Test, and partial least squares structural equation modelling. The findings, supported by various reliability, validity and fit indices, demonstrate that EI competencies related to self-awareness, self-management and relationship management significantly contribute to the performance of construction organisations. This study enriches the existing body of knowledge on EI by providing a framework that connects EI competencies with organisational performance in the South African construction context, an area that has been largely underexplored.
On the Way to Accounting for Lung Modulation Effects in Particle Therapy of Lung Cancer Patients—A Review
Authors: Witt Matthias , Weber Uli , Flatten Veronika , Stolzenberg Jessica , Engenhart-Cabillic Rita , Zink Klemens , Baumann Kilian-Simon
Published: October 2024

Particle therapy presents a promising alternative to conventional photon therapy for treating non-small cell lung cancer (NSCLC). However, the heterogeneous structure of lung tissue leads to the degradation of the Bragg peak and thereby to the degradation of the dose distribution. This review offers a comprehensive overview of the models developed to account for these modulation effects. It summarizes studies focused on determining modulation power as a predictor of this so-called lung modulation. In addition, the review covers early investigations on dose uncertainties caused by lung modulation in CT-based lung phantoms and patient anatomies and discusses future challenges in integrating these solutions into clinical treatment planning routines.
Receptor for Hyaluronan Mediated Motility (RHAMM)/Hyaluronan Axis in Breast Cancer Chemoresistance
Authors: Fujisawa Shiori , Takagi Kiyoshi , Yamaguchi-Tanaka Mio , Sato Ai , Miki Yasuhiro , Miyashita Minoru , Tada Hiroshi , Ishida Takanori , Suzuki Takashi
Published: October 2024

Background/Objectives: Receptor for hyaluronan-mediated motility (RHAMM) is a hyaluronan (HA) receptor, which exerts diverse biological functions in not only physiological but also pathological conditions in human malignancies, including breast cancer. Although chemoresistance is a significant clinical challenge in breast cancer, a possible contribution of RHAMM and hyaluronan to breast cancer chemoresistance has remained unclear. Methods: We immunolocalized RHAMM and HA in breast carcinoma tissues. Also, we utilized epirubicin-sensitive (parental) and rpirubicin-resistant (EPIR) breast cancer cell lines to explore the role of RHAMMM in breast cancer progression. Results: We found out that RHAMM and HA were cooperatively correlated with breast cancer aggressiveness and recurrence after chemotherapy. In vitro studies demonstrated that RHAMM was overexpressed in EPIR cells compared to parental cells. In addition, the knockdown of RHAMM significantly suppressed proliferation and migration of both parental and EPIR cells. On the other hand, the expression level of cancer stem cell marker CD44, which was overexpressed in M-EPIR (epirubicin-resistant MCF-7 subline) compared to MCF-7, was significantly suppressed by knockdown of RHAMM. In addition, the knockdown of RHAMM significantly altered the expression of N-cadherin and E-cadherin, leading to an epithelial phenotype. Conclusions: Aberrant RHAMM signaling were considered to cause chemoresistance related to cancer stemness and epithelial to mesenchymal transition, and increased cell proliferation and migration of both chemo-sensitive and chemo-resistant breast cancer cells.
Real-Life Comparative Analysis of Robotic-Assisted Versus Laparoscopic Radical Prostatectomy in a Single Centre Experience
Authors: Salciccia Stefano , Santarelli Valerio , Di Pierro Giovanni Battista , Del Giudice Francesco , Bevilacqua Giulio , Di Lascio Giovanni , Gentilucci Alessandro , Corvino Roberta , Brunelli Valentina , Basile Greta , Scornajenghi Carlo Maria , Santodirocco Lorenzo , Gobbi Luca , Rosati Davide , Moriconi Martina , Panebianco Valeria , Magliocca Fabio Massimo , Santini Daniele , Di Civita Mattia Alberto , Forte Flavio , Frisenda Marco , Franco Giorgio , Sciarra Alessandro
Published: October 2024

Background: The advantage of a robotic-assisted (RARP) over a laparoscopic (LRP) approach in radical prostatectomy (RP) remains to be demonstrated. Aim: The aim of the study is to use a homogeneous population in real life and single primary surgeon surgery to analyze the oncological and functional results based on the type of surgical approach and pathological features. Methods: This is a prospective trial on non-metastatic prostate cancer (PCa) patients considered after a multidisciplinary decision to conduct a RP, using a RARP or LRP approach. A real-life setting was analyzed at our Urological Departments using homogeneous criteria for the management of PCa cases and a single surgeon experience on 444 cases (284 LRP and 160 RARP). Results: Mean operating time was significantly lower in RARP (153.21 ± 25.1 min) than in LRP (173.33 ± 44.3 min) (p < 0.001). In cases submitted to an extended lymph node dissection (eLND), the mean number of lymph nodes removed was 15.16 ± 7.83 and 19.83 ± 4.78, respectively, in LRP and RARP procedures (p < 0.001), but positive lymph nodes (pN1) were similarly found in 15.8% of LRP patients and 13.6% of RARP patients (p = 0.430). Surgical margins (SM) positivity was not significantly higher in the RARP group (20.0%) when compared to the LRP group (15.9%) (p = 0.145). During the postoperative follow-up, a biochemical recurrence (BCR) was detected in 14.4% and 7.5% of cases in the LRP and RARP group, respectively, (p = 0.014). Better results of PAD tests at 3-month intervals using the RARP approach (mean pad weight 75.57 ± 122 g and 14 ± 42 g, respectively, in LRP and RARP (p < 0.01)) were described. Conclusions: In the comparison between the RARP and LRP approach, a clear advantage of the robotic approach is a significant reduction in operating times, days of hospitalization, and postoperative catheterization compared to laparoscopic surgery. It is not possible to describe any certain oncological advantage both in terms of surgical margins and pathological lymph nodes removed. In RARP cases a reduction to the limit of significance is described in terms of biochemical recurrence. RARP produces a more rapid recovery of urinary continence at 3 months postoperatively without significant advantages in terms of erective potency recovery.
Computer-Aided Identification and Design of Ligands for Multi-Targeting Inhibition of a Molecular Acute Myeloid Leukemia Network
Authors: Asfa Seyedeh Sadaf , Arshinchi Bonab Reza , Önder Onur , Uça Apaydın Merve , Döşeme Hatice , Küçük Can , Georgakilas Alexandros G. , Stadler Bernhard M. , Logotheti Stella , Kale Seyit , Pavlopoulou Athanasia
Published: October 2024

Background/Objectives: Acute myeloid leukemia (AML) is characterized by therapeutic failure and long-term risk for disease relapses. As several therapeutic targets participate in networks, they can rewire to eventually evade single-target drugs. Hence, multi-targeting approaches are considered on the expectation that interference with many different components could synergistically hinder activation of alternative pathways and demolish the network one-off, leading to complete disease remission. Methods: Herein, we established a network-based, computer-aided approach for the rational design of drug combinations and de novo agents that interact with many AML network components simultaneously. Results: A reconstructed AML network guided the selection of suitable protein hubs and corresponding multi-targeting strategies. For proteins responsive to existing drugs, a greedy algorithm identified the minimum amount of compounds targeting the maximum number of hubs. We predicted permissible combinations of amiodarone, artenimol, fostamatinib, ponatinib, procaine, and vismodegib that interfere with 3–8 hubs, and we elucidated the pharmacological mode of action of procaine on DNMT3A. For proteins that do not respond to any approved drugs, namely cyclins A1, D2, and E1, we used structure-based de novo drug design to generate a novel triple-targeting compound of the chemical formula C15H15NO5, with favorable pharmacological and drug-like properties. Conclusions: Overall, by integrating network and structural pharmacology with molecular modeling, we determined two complementary strategies with the potential to annihilate the AML network, one in the form of repurposable drug combinations and the other as a de novo synthesized triple-targeting agent. These target–drug interactions could be prioritized for preclinical and clinical testing toward precision medicine for AML.
Clinical and Molecular Characteristics and Outcome of Adult Medulloblastoma at a Tertiary Cancer Center
Authors: Almousa Abdelatif , Erjan Ayah , Sarhan Nasim , Obeidat Mouness , Alshorbaji Amer , Amarin Rula , Alawabdeh Tala , Abu-Hijlih Ramiz , Mujlli Mohammad , Kh. Ibrahimi Ahmad , Abu Laban Dima , Maraqa Bayan , Al-Ani Abdallah , Al Sharie Sarah , Al-Hussaini Maysa
Published: October 2024

Background/Objectives: Adult medulloblastoma is a rare entity, with management data extrapolated from pediatric medulloblastoma cases. We aim to report the clinical characteristics, prognostic factors, and treatment outcome of a cohort of adult patients with medulloblastoma. Methods: Fifty-three patients aged ≥ 18 years with medulloblastoma treated at King Hussein Cancer Center between 2007 and 2019 were retrospectively reviewed. Patients’ diseases were staged according to modified Chang’s staging system. All patients received adjuvant craniospinal irradiation followed by a posterior fossa boost. Baseline disease characteristics, including molecular subgrouping, were tested as prognostic factors of progression-free survival (PFS) and overall survival (OS) by using univariate analysis. Results: Median follow-up was 70 months (range 37.5–104.5 months). Twenty-two tumors were of the SHH-activated subtype. Conversely, WNT-activated and group 4 tumors had three cases each. Only 37.7% of patients died. The mean 3-year, 5-year, and 10-year OS were 85% (75–95%), 74% (62–87%), and 50% (33–75%), respectively. Significant differences in OS were associated with the extent of surgery (p = 0.017), M stage (p = 0.009), and risk status (p < 0.001). Relapses were detected in 28.3% of cases. The 3-year, 5-year, and 10-year PFS were 81% (71–92%), 75% (63–88%), and 66% (52–83%), respectively. Significant differences in PFS were associated with the extent of surgery (p = 0.008) and risk status (p = 0.012). Molecular subgrouping did not correlate with OS or PFS. Conclusions: Our results revealed poor survival of patients with high-risk disease, which may necessitate the intensification of chemotherapy. Molecular subgrouping did not correlate with the outcome in this cohort.
Catalytic Degradation of Bisphenol A in Water by Non-Thermal Plasma Coupled with Persulfate
Authors: Zhang Han , Yang Shuang , Cui Jiayu , Guo He
Published: October 2024

Bisphenol A (BPA) has become prevalent in the environment due to its extensive use in industrial materials, thus raising significant concerns regarding its potential toxicity and health effects. In this study, an efficient and eco-friendly non-thermal plasma (NTP) was used to catalyze persulfate (PS) for BPA decomposition, and the results showed that the integrated system could effectively degrade BPA. The best performance was attained at a PS to BPA mass ratio of 5:1, with a degradation rate of 91.3% following a 30 min treatment. The degradation rate of BPA increased with increasing input voltage and frequency; conversely, it decreased with an increase in BPA’s initial concentration. Higher BPA degradation rates could be achieved in alkaline environments. Radical quenching experiments revealed that SO4−•, OH•, O2−• and 1O2 were important active substances involved in BPA degradation. Nine intermediate products were identified by liquid chromatography–mass spectrometry (LC-MS), and four degradation pathways were deduced. Additionally, a toxicity analysis of intermediate products was performed. The significant decrease in chemical oxygen demand (COD) during the actual wastewater treatment suggested that the NTP/PS system has good applicability in actual wastewater treatment.
Structure–Function Correlation in Cobalt-Induced Brain Toxicity
Authors: Obied Basel , Richard Stephen , Zahavi Alon , Fixler Dror , Girshevitz Olga , Goldenberg-Cohen Nitza
Published: October 2024

Cobalt toxicity is difficult to detect and therefore often underdiagnosed. The aim of this study was to explore the pathophysiology of cobalt-induced oxidative stress in the brain and its impact on structure and function. Thirty-five wild-type C57B16 mice received intraperitoneal cobalt chloride injections: a single high dose with evaluations at 24, 48, and 72 h (n = 5, each) or daily low doses for 28 (n = 5) or 56 days (n = 15). A part of the 56-day group also received minocycline (n = 5), while 10 mice served as controls. Behavioral changes were evaluated, and cobalt levels in tissues were measured with particle-induced X-ray emission. Brain sections underwent magnetic resonance imaging (MRI), electron microscopy, and histological, immunohistochemical, and molecular analyses. High-dose cobalt caused transient illness, whereas chronic daily low-dose administration led to long-term elevations in cobalt levels accompanied by brain inflammation. Significant neurodegeneration was evidenced by demyelination, increased blood–brain barrier permeability, and mitochondrial dysfunction. Treated mice exhibited extended latency periods in the Morris water maze test and heightened anxiety in the open field test. Minocycline partially mitigated brain injury. The observed signs of neurodegeneration were dose- and time-dependent. The neurotoxicity after acute exposure was reversible, but the neurological and functional changes following chronic cobalt administration were not.
Newborn Genomic Sequencing Needs Confirmation but Not Repeating
Authors: Bennetts Bruce , Ho Gladys , Shin Sarah , Cheong Pak Leng , Wotton Tiffany , Ranieri Enzo , Pirreca Shelley
Published: October 2024

Newborn screening (NBS) has been one of the big innovations in public health. It has grown over the decades, especially with the introduction of tandem mass spectrometry. However, it is likely to expand significantly in the coming decades with the introduction of genomic testing. Traditionally, in NBS, there has been a pattern of repeat testing for confirmation and follow-up diagnostic testing. This follow-up is critical as NBS is a screening program. This pathway is appropriate for low-cost tests, but if public health authorities are going to invest in high-cost screening such as whole-genome sequencing, they are likely to baulk at repeating these expensive tests in a diagnostic setting. Our study investigates whether screening-grade data from NBS can be transitioned into diagnostic-grade data using a panel of single-nucleotide variants (SNVs) on a diagnostic specimen. These SNVs could be used to link the diagnostic specimen with all of the provenance requirements associated with routine pathology and the NBS genomic data. This strategy has large cost benefits and opens up the rapid use of NBS genomic data should a child present in an acute care setting and a genetic diagnosis is suspected. This approach will greatly speed up the confirmation of positive NBS results and reduce family anxiety due to delayed diagnostic testing.
Exploring the Relationship Between Play During School Recess and Motor Performance in 6- to 8-Year-Old Children
Authors: Derikx Dagmar F. A. A. , Schoemaker Marina M. , Faber Leila , Houwen Suzanne , Hartman Esther
Published: October 2024

Background: Playing with others, which in school occurs mainly during recess, might be an enabling factor to improve children’s motor performance, as behaviour is shaped by observing and imitating others. Objective: The aim of the current study was to examine whether children’s play activities and with whom 6- to 8-year-old children play during recess are related to their motor performance. Methods: The study sample consisted of 86 Dutch participants (mean age 6.92 ± 0.62 years, 58.1% boys). A modified version of the System for Observing Children’s Activity and Relationships during Play was used to observe the following play variables: sedentary or active behaviour, group size, activity type, and type of interaction. The Movement Assessment Battery for Children 2 was used to measure three components of motor performance: Manual Dexterity, Aiming and Catching, and Balance. Associations between the play variables and the motor components were investigated using compositional data analysis and logistic regressions. Results: The results showed that children who spent more time in sedentary behaviour rather than in active behaviour were less likely to have motor difficulties in the Aiming and Catching component. None of the other play variables were related to motor performance. Conclusions: One explanation might be that these play variables in itself are not related to motor performance, but that these variables should be investigated as an integrated whole rather than in isolation. Therefore, future research should investigate whether interactions between the play variables are related to motor performance.
Neonatal Hearing Screening Using Wideband Absorbance and Otoacoustic Emissions Measured Under Ambient and Pressurized Conditions
Authors: Novelli Carolina Verônica Lino , Sanfins Milaine Dominici , Skarżyński Piotr Henryk , Skarżyńska Magdalena Beata , Diniz-Hein Thaís Antonelli , Colella-Santos Maria Francisca
Published: October 2024

Background: The objective was to analyze wideband acoustic absorbance and transiently evoked otoacoustic emissions (TEOAEs) from newborns without risk indicators of hearing loss and test the effectiveness of measuring TEOAEs under pressurized ear canal conditions. Methods: Evaluation of 102 newborns from a maternity hospital, who stayed in the well-baby nursery and did not have risk indicators for hearing loss. The procedures involved wideband tympanometry and TEOAEs performed at ambient pressure (AP) and at a pressure corresponding to maximum compliance (PP). Newborns were then divided into three groups according to their AP and PP results: G1 (PASS/PASS), G2 (FAIL/PASS), and G3 (FAIL/FAIL). Results: Comparing the three groups, pressurization improved the pass rate for G2 only. For wideband absorbance, differences were statistically significant for frequencies of 2, 3, and 6 kHz, with lower values under the AP condition. For TEOAEs, the differences were statistically significant in all bands, with lower values under the AP condition. Conclusions: Pressurization was effective in detecting more TEOAEs in G2, thus reducing the number of failures in neonatal hearing screening and reducing the need to return for retesting.
The Role of Fairness for Accepting Stricter Carbon Taxes in Sweden
Authors: Lindvall Daniel , Sörqvist Patrik , Jagers Sverker Carlsson , Karlsson Mikael , Sjöberg Stefan , Barthel Stephan
Published: October 2024

Carbon taxes are considered to be an efficient method to reduce greenhouse gas emissions; however, such taxes are generally unpopular, partly because they are seen as unfair. To explore if public acceptance of a stricter carbon tax in Sweden can be enhanced, this study investigates the effectiveness of three different policy designs, addressing collective and personal distributional consequences and promoting procedural aspects (democratic influence). A large-scale (n = 5200) survey is applied, combining a traditional multi-category answer format with a binary choice format. The results show that support for higher carbon taxation can be enhanced if tax revenues are redistributed to affected groups. Policies with collective justice framings can change the attitudes of individuals who express antagonistic attitudes to increased carbon taxation and influence groups comparably more affected by carbon taxes, such as rural residents, low-income groups, and people who are driving long distances. Policy designs addressing collective distributional consequences are, however, less effective on individuals expressing right-leaning ideological views and low environmental concern. Policies addressing personal distributional outcomes, or perceptions of procedural injustice, had no significant effect on policy acceptance.
System 2 Thinking in OpenAI’s o1-Preview Model: Near-Perfect Performance on a Mathematics Exam
Authors: de Winter Joost C. F. , Dodou Dimitra , Eisma Yke Bauke
Published: October 2024

The processes underlying human cognition are often divided into System 1, which involves fast, intuitive thinking, and System 2, which involves slow, deliberate reasoning. Previously, large language models were criticized for lacking the deeper, more analytical capabilities of System 2. In September 2024, OpenAI introduced the o1 model series, designed to handle System 2-like reasoning. While OpenAI’s benchmarks are promising, independent validation is still needed. In this study, we tested the o1-preview model twice on the Dutch ‘Mathematics B’ final exam. It scored a near-perfect 76 and 74 out of 76 points. For context, only 24 out of 16,414 students in the Netherlands achieved a perfect score. By comparison, the GPT-4o model scored 66 and 62 out of 76, well above the Dutch students’ average of 40.63 points. Neither model had access to the exam figures. Since there was a risk of model contamination (i.e., the knowledge cutoff for o1-preview and GPT-4o was after the exam was published online), we repeated the procedure with a new Mathematics B exam that was published after the cutoff date. The results again indicated that o1-preview performed strongly (97.8th percentile), which suggests that contamination was not a factor. We also show that there is some variability in the output of o1-preview, which means that sometimes there is ‘luck’ (the answer is correct) or ‘bad luck’ (the output has diverged into something that is incorrect). We demonstrate that the self-consistency approach, where repeated prompts are given and the most common answer is selected, is a useful strategy for identifying the correct answer. It is concluded that while OpenAI’s new model series holds great potential, certain risks must be considered.
Evaluation of Safety and Efficacy of Chemical Peels With and Without Sonophoresis on Selected Skin Parameters—A Prospective Comparative Study
Authors: Sołdacka Dorota , Barańska-Rybak Wioletta
Published: October 2024

Background: Skin is the largest organ in the human body. Some skin parameters like moisturization and sebum secretion play a vital role in the skin’s functioning. This study aims to assess the effects of topical chemical peels of different concentrations and pH, applied manually and with ultrasounds, on the level of hydration, erythema, pigmentation, and sebum secretion of the skin. Methods: The study involved 90 Caucasian females, aged 25 to 59, with dry, dehydrated skin, skin with erythema or pigmentation disorders. The patients were randomly divided into three equal groups. The subjects from Group A were applied 10% mandelic acid with 25% gluconolactone of pH 4.0 manually. In Group B, 40% mandelic acid of pH 1.5 was used. The subjects from Group C were applied 10% mandelic acid with 25% gluconolactone of pH 4.0 via sonophoresis. A series of six procedures in weekly intervals was performed. Skin functional parameters (skin hydration, erythema, and melanin indicators) were taken before the first procedure, after 14 days, 28 days, and 42 days. Results: In Group A, the level of moisturization of the skin increased statistically significantly (p = 0.0100) however, the sebum secretion and erythema did not change. In Group B, the level of moisturization improved statistically significantly, as well as erythema (p = 0.0001). Sebum secretion in the final measurement increased. The moisturization and erythema in Group C did not differ statistically significantly. On the other hand, the sebum secretion increased significantly. Conclusions: Very superficial chemical peels significantly alter selected skin parameters. AHAs and PHAs applied using the ultrasound method do not affect the level of hydration, erythema, or pigmentation of the skin.