bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavior of Anchors Embedded in Concrete Damaged by the Maximum Considered Earthquake: An Experimental Study
Authors: Kabantsev Oleg , Kovalev Mikhail
Published: November 2023

The article presents experimental tests carried out to investigate the effect of crack width (0.4, 0.8, 1.5, and 3.0 mm) on the behavior of anchor bolts under static and dynamic loading. Ultimate loads for anchors reached 220 kN depending on the anchor type, the diameter, and the crack opening width. Mechanical and bonded anchors were studied as the most frequently used anchor types. Two states of concrete, resulting from the design earthquake and the maximum considered earthquake, were simulated in the course of the experiments. Within the framework of the study, dependencies between the bearing capacity and stiffness of anchorages, on the one hand, and the level of concrete damage, on the other hand, were identified for different types of anchors. The data, generated in the course of the study, were used to identify the types of anchorages recommended for embedment in seismic areas. Plasticity coefficients and seismic load reduction coefficients were determined for different types of anchors and levels of concrete damage as a result of experimental studies. Reduction coefficients can be contributed to the design of anchorages embedded in seismic areas.
Prediction and Optimization of Thermal Loads in Buildings with Different Shapes by Neural Networks and Recent Finite Difference Methods
Authors: Askar Ali Habeeb , Kovács Endre , Bolló Betti
Published: November 2023

This study aimed to estimate the heating load (HL) and the cooling load (CL) of a residential building using neural networks and to simulate the thermal behavior of a four-layered wall with different orientations. The neural network models were developed and tested using Multi-Layer Perceptron (MLP) and Radial Basis (RB) networks with three algorithms, namely the Levenberg-Marquardt (LM), the Scaled Conjugate Gradient (SCG), and the Radial Basis Function (RB). To generate the data, 624 models were used, including six building shapes, four orientations, five glazing areas, and five ways of distributing glazing. The LM model showed the best accuracy compared to the experimental data. The L-shape facing south with windows on the east and south sides and a 20% window area was found to be the best shape for balancing the lighting and ventilation requirements with the heating and cooling loads near the mean value. The heating and cooling loads for this shape were 22.5 kWh and 24.5 kWh, respectively. The simulation part used the LH algorithm coded in MATLAB to analyze the temperature and heat transfer across the wall layers and the effect of solar radiation. The maximum and minimum percentage differences obtained by HAP are 10.7% and 2.7%, respectively. The results showed that the insulation layer and the wall orientation were important factors for optimizing the thermal comfort of a building. This study demonstrated the effectiveness of neural networks and simulation methods for building energy analysis.
Strengthening Effect of the Fixing Method of Polypropylene Band on Unreinforced Brick Masonry in Flexural, Shear, and Torsion Behaviors
Authors: Hung Ta Quy , Mizoguchi Mitsuo , Takase Yuya
Published: November 2023

Every year, Vietnam faces typhoons accompanied by strong winds. Semi-permanent houses are severely damaged by these winds. We researched a strengthening method using a Polypropylen (PP) band to prevent housing damage caused by strong winds. In this study, we have developed a new method of fixing PP band to bricks. The PP band is sandwiched between two flat steel washers and fastened with steel screws to a plastic plug embedded in the side of the brick. A total of 49 specimens were used to study the influence of the PP band on the flexural, shear, and torsional behaviors of brick masonry. In the flexural tests, the results show that the average load-carrying capacity at ultimate failure and deflection at first crack of the PP band specimens was 1.7 and 1.62 times, respectively, higher than those of non-PP band specimens. In the shear tests, the tests on the strengthened specimens showed an increase in the shear strength for all pre-compression ranges of 0.2–0.6 N/mm2. However, it was not significant. Similarly, the initial stiffness was not significantly affected by the pre-compression level in both the reinforced and unreinforced cases. In the torsion tests, the improvements in the average load-carrying capacity and deformation ability at the first crack were 1.21 times and 1.47 times, respectively. In the reinforced specimens, at ultimate failure, a slight increase in load was observed, but it did not exceed the initial peak load.
Machine Learning Model of ResNet50-Ensemble Voting for Malignant–Benign Small Pulmonary Nodule Classification on Computed Tomography Images
Authors: Li Weiming , Yu Siqi , Yang Runhuang , Tian Yixing , Zhu Tianyu , Liu Haotian , Jiao Danyang , Zhang Feng , Liu Xiangtong , Tao Lixin , Gao Yan , Li Qiang , Zhang Jingbo , Guo Xiuhua
Published: November 2023

Background: The early detection of benign and malignant lung tumors enabled patients to diagnose lesions and implement appropriate health measures earlier, dramatically improving lung cancer patients’ quality of living. Machine learning methods performed admirably when recognizing small benign and malignant lung nodules. However, exploration and investigation are required to fully leverage the potential of machine learning in distinguishing between benign and malignant small lung nodules. Objective: The aim of this study was to develop and evaluate the ResNet50-Ensemble Voting model for detecting the benign and malignant nature of small pulmonary nodules (<20 mm) based on CT images. Methods: In this study, 834 CT imaging data from 396 patients with small pulmonary nodules were gathered and randomly assigned to the training and validation sets in an 8:2 ratio. ResNet50 and VGG16 algorithms were utilized to extract CT image features, followed by XGBoost, SVM, and Ensemble Voting techniques for classification, for a total of ten different classes of machine learning combinatorial classifiers. Indicators such as accuracy, sensitivity, and specificity were used to assess the models. The collected features are also shown to investigate the contrasts between them. Results: The algorithm we presented, ResNet50-Ensemble Voting, performed best in the test set, with an accuracy of 0.943 (0.938, 0.948) and sensitivity and specificity of 0.964 and 0.911, respectively. VGG16-Ensemble Voting had an accuracy of 0.887 (0.880, 0.894), with a sensitivity and specificity of 0.952 and 0.784, respectively. Conclusion: Machine learning models that were implemented and integrated ResNet50-Ensemble Voting performed exceptionally well in identifying benign and malignant small pulmonary nodules (<20 mm) from various sites, which might help doctors in accurately diagnosing the nature of early-stage lung nodules in clinical practice.
Tooth Abnormalities and Their Age-Dependent Occurrence in Leukemia Survivors
Authors: Jodłowska Anna , Postek-Stefańska Lidia
Published: November 2023

The multidrug nature of anticancer treatment and different treatment protocols used in the studies are likely to be a major limitation in establishing real risk factors determining the occurrence of dental abnormalities. The authors aimed to establish a relationship between the duration and the dose of chemotherapy and the number of tooth adverse effects in the group receiving the same treatment. Of the 40 anticancer therapy recipients who attended the outpatient dental clinic, 7 leukemia survivors receiving the treatment according to the ALL IC-BFM 2002 protocol were selected. The study group consisted of four females and three males aged 92 to 207 months at the time of dental examination and 29 to 91 months at leukemia diagnosis. As a result of the clinical and radiological examination, dental abnormalities such as agenesis, tooth size reduction, root abnormalities, and taurodontia were identified, and the medical records of all survivors were reviewed in terms of drugs administered, their doses, and treatment schedules. No correlation was observed between the treatment duration of an intensive therapy, the entire therapy, and the number of tooth abnormalities. No relationship was also found between the number of dental abnormalities and the cumulative dose of vincristine, L-asparaginase, methotrexate, cyclophosphamide, cytarabine, and 6-mercaptopurine. The age at the onset of antineoplastic therapy is likely to be the strongest risk factor for toxic injury during tooth development.
STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs
Authors: Chiriac Mircea T. , Hracsko Zsuzsanna , Becker Christoph , Neurath Markus F.
Published: November 2023

Colorectal cancer (CRC) is a significant socioeconomic burden in modern society and is accountable for millions of premature deaths each year. The role of signal transducer and activator of transcription 2 (STAT2)-dependent signaling in this context is not yet fully understood, and no therapies targeting this pathway are currently being pursued. We investigated the role of STAT2 in CRC using experimental mouse models coupled with RNA-sequencing (RNA-Seq) data and functional assays with anti-cancer agents in three-dimensional tumoroids. Stat2−/− mice showed greater resistance to the development of CRC in both inflammation-driven and inflammation-independent experimental CRC models. In ex vivo studies, tumoroids derived from Stat2−/− mice with the multiple intestinal neoplasia (Min) mutant allele of the adenomatous polyposis coli (Apc) locus exhibited delayed growth, were overall smaller and more differentiated as compared with tumoroids from ApcMin/+ wildtype (WT) mice. Notably, tumoroids from ApcMin/+ Stat2−/− mice were more susceptible to anti-cancer agents inducing cell death by different mechanisms. Our findings clearly indicated that STAT2 promotes CRC and suggested that interventions targeting STAT2-dependent signals might become an attractive therapeutic option for patients with CRC.
A Radiomics-Based Machine Learning Perspective on the Parotid Gland as a Potential Surrogate Marker for HPV in Oropharyngeal Cancer
Authors: Prasse Gordian , Glaas Agnes , Meyer Hans-Jonas , Zebralla Veit , Dietz Andreas , Hering Kathrin , Kuhnt Thomas , Denecke Timm
Published: November 2023

Background: In treatment of oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus status (HPV) plays a crucial role. The HPV-positive subtype tends to affect younger patients and is associated with a more favorable prognosis. HPV-associated lesions have been described in the parotid gland, which is included in routine imaging for OPSCC. This work aims to explore the ability of an ML system to classify HPV status based on imaging of the parotid gland, which is routinely depicted on staging imaging. Methods: Using a radiomics approach, we investigate the ability of five contemporary machine learning (ML) models to distinguish between HPV-positive and HPV-negative OPSCC based on non-contrast computed tomography (CT) data of tumor volume (TM), locoregional lymph node metastasis (LNM), and the parotid gland (Parotid). After exclusion of cases affected by streak artefacts, 53 patients (training set: 39; evaluation set: 14) were retrospectively evaluated. Classification performances were tested for significance against random optimistic results. Results: The best results are AUC 0.71 by XGBoost (XGB) for TM, AUC 0.82 by multi-layer perceptron (MLP) for LNM, AUC 0.76 by random forest (RF) for Parotid, and AUC 0.86 by XGB for a combination of all three regions of interest (ROIs). Conclusions: The results suggest involvement of the parotid gland in HPV infections of the oropharyngeal region. While the role of HPV in parotid lesions is under active discussion, the migration of the virus from the oral cavity to the parotid gland seems plausible. The imaging of the parotid gland offers the benefit of fewer streak artifacts due to teeth and dental implants and the potential to screen for HPV in cases of an absent or unlocatable tumor. Future investigation can be directed to validation of the results in independent datasets and to the potential of improvement of current classification models by addition of information based on the parotid gland.
Understanding the Role of Activation Loop Mutants in Drug Efficacy for FLT3-ITD
Authors: Kazi Julhash U. , Al Ashiri Lina , Purohit Rituraj , Rönnstrand Lars
Published: November 2023

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants. Utilizing the ConPLex platform, over 5.7 million unique FLT3 activation loop mutants—small molecule pairs were analyzed. The binding free energies of three inhibitors were assessed, and cellular apoptotic responses were evaluated under drug treatments. Notably, the introduction of the Xepto50 scoring system provides a nuanced metric for drug efficacy. The findings underscore the modulation of molecular interactions and cellular responses by Y842 mutations in FLT3-KD, highlighting the need for tailored therapeutic approaches in FLT3-ITD-related malignancies.
Krüppel-like Factor 5 Plays an Important Role in the Pathogenesis of Chronic Pancreatitis
Authors: Alavi Maryam , Mejia-Bautista Ana , Tang Meiyi , Bandovic Jela , Rosenberg Avi Z. , Bialkowska Agnieszka B.
Published: November 2023

Chronic pancreatitis results in the formation of pancreatic intraepithelial neoplasia (PanIN) and poses a risk of developing pancreatic cancer. Our previous study demonstrated that Krüppel-like factor 5 (KLF5) is necessary for forming acinar-to-ductal metaplasia (ADM) in acute pancreatitis. Here, we investigated the role of KLF5 in response to chronic injury in the pancreas. Human tissues originating from chronic pancreatitis patients showed increased levels of epithelial KLF5. An inducible genetic model combining the deletion of Klf5 and the activation of KrasG12D mutant expression in pancreatic acinar cells together with chemically induced chronic pancreatitis was used. The chronic injury resulted in increased levels of KLF5 in both control and KrasG12D mutant mice. Furthermore, it led to numerous ADM and PanIN lesions and extensive fibrosis in the KRAS mutant mice. In contrast, pancreata with Klf5 loss (with or without KrasG12D) failed to develop ADM, PanIN, or significant fibrosis. Furthermore, the deletion of Klf5 reduced the expression level of cytokines and fibrotic components such as Il1b, Il6, Tnf, Tgfb1, Timp1, and Mmp9. Notably, using ChIP-PCR, we showed that KLF5 binds directly to the promoters of Il1b, Il6, and Tgfb1 genes. In summary, the inactivation of Klf5 inhibits ADM and PanIN formation and the development of pancreatic fibrosis.
Side Effects from Cancer Therapies and Perspective of 1044 Long-Term Ovarian Cancer Survivors—Results of Expression VI–Carolin Meets HANNA–Holistic Analysis of Long-Term Survival with Ovarian Cancer: The International NOGGO, ENGOT, and GCIG Survey
Authors: Woopen Hannah , Keller Maren , Zocholl Dario , Mittelstadt Suzana , Barretina-Ginesta Maria-Pilar , Heinzelmann-Schwarz Viola , Lafleur Judith , Kocián Roman , Baum Joanna , Krabisch Petra , Achimas-Cadariu Patriciu , Vardar Mehmet Ali , Vergote Ignace , Nasser Sara , Link Theresa , Gil-Martin Marta , Zwimpfer Tibor A. , Leitner Katharina , Jedryka Marcin , Boxler Tamara , Braicu Elena Ioana , Sehouli Jalid
Published: November 2023

The aim of this survey was to increase the knowledge on the characteristics and health concerns of long-term survivors (LTS; survival > 5 years) after ovarian cancer in order to tailor follow-up care. This international survey was initiated by the NOGGO and was made available to members of ENGOT and GCIG. The survey is anonymous and consists of 68 questions regarding sociodemographic, medical (cancer) history, health concerns including distress, long-term side effects, and lifestyle. For this analysis, 1044 LTS from 14 countries were recruited. In total, 58% were diagnosed with FIGO stage III/IV ovarian cancer and 43.4% developed recurrent disease, while 26.0% were receiving cancer treatment at the time of filling in the survey. LTS who survived 5–10 years self-estimated their health status as being significantly worse than LTS who survived more than 10 years (p = 0.034), whereas distress also remained high 10 years after cancer diagnosis. Almost half of the cohort (46.1%) reported still having symptoms, which were mainly lymphedema (37.7%), fatigue (23.9%), pain (21.6%), polyneuropathy (16.9%), gastrointestinal problems (16.6%), and memory problems (15.5%). Almost all patients (94.2%) regularly received follow-up care. Specialized survivorship care with a focus on long-term side effects, lifestyle, and prevention should be offered beyond the typical five years of follow-up care.
C-Reactive Protein as an Early Predictor of Efficacy in Advanced Non-Small-Cell Lung Cancer Patients: A Tumor Dynamics-Biomarker Modeling Framework
Authors: Nassar Yomna M. , Ojara Francis Williams , Pérez-Pitarch Alejandro , Geiger Kimberly , Huisinga Wilhelm , Hartung Niklas , Michelet Robin , Holdenrieder Stefan , Joerger Markus , Kloft Charlotte
Published: November 2023

In oncology, longitudinal biomarkers reflecting the patient’s status and disease evolution can offer reliable predictions of the patient’s response to treatment and prognosis. By leveraging clinical data in patients with advanced non-small-cell lung cancer receiving first-line chemotherapy, we aimed to develop a framework combining anticancer drug exposure, tumor dynamics (RECIST criteria), and C-reactive protein (CRP) concentrations, using nonlinear mixed-effects models, to evaluate and quantify by means of parametric time-to-event models the significance of early longitudinal predictors of progression-free survival (PFS) and overall survival (OS). Tumor dynamics was characterized by a tumor size (TS) model accounting for anticancer drug exposure and development of drug resistance. CRP concentrations over time were characterized by a turnover model. An x-fold change in TS from baseline linearly affected CRP production. CRP concentration at treatment cycle 3 (day 42) and the difference between CRP concentration at treatment cycles 3 and 2 were the strongest predictors of PFS and OS. Measuring longitudinal CRP allows for the monitoring of inflammatory levels and, along with its reduction across treatment cycles, presents a promising prognostic marker. This framework could be applied to other treatment modalities such as immunotherapies or targeted therapies allowing the timely identification of patients at risk of early progression and/or short survival to spare them unnecessary toxicities and provide alternative treatment decisions.
Prognostic Impact of Copy Number Alterations’ Profile and AID/RAG Signatures in Acute Lymphoblastic Leukemia (ALL) with BCR::ABL and without Recurrent Genetic Aberrations (NEG ALL) Treated with Intensive Chemotherapy
Authors: Libura Marta , Karabin Karolina , Tyrna Paweł , Czyż Anna , Makuch-Łasica Hanna , Jaźwiec Bożena , Paluszewska Monika , Piątkowska-Jakubas Beata , Zawada Magdalena , Gniot Michał , Trubicka Joanna , Szymańska Magdalena , Borg Katarzyna , Więsik Marta , Czekalska Sylwia , Florek Izabela , Król Maria , Paszkowska-Kowalewska Małgorzata , Gil Lidia , Kapelko-Słowik Katarzyna , Patkowska Elżbieta , Tomaszewska Agnieszka , Mądry Krzysztof , Machowicz Rafał , Czerw Tomasz , Piekarska Agnieszka , Dutka Magdalena , Kopińska Anna , Helbig Grzegorz , Gromek Tomasz , Lewandowski Krzysztof , Zacharczuk Marta , Pastwińska Anna , Wróbel Tomasz , Haus Olga , Basak Grzegorz , Hołowiecki Jerzy , Juszczyński Przemysław , Lech-Marańda Ewa , Giebel Sebastian , Jędrzejczak Wiesław Wiktor
Published: November 2023

Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.
Chiral Catalysts for the Enantioselective Carbon Dioxide-Based Cyclic Carbonates and Polycarbonates
Authors: Altava Belén , Cirujano Francisco G. , García-Verdugo Eduardo
Published: November 2023

Using carbon dioxide as a feedstock for synthesizing organic molecules with added value can contribute to a more sustainable chemical industry since CO2 is an abundant, inexpensive, and nontoxic renewable carbon resource. In this regard, the synthesis of cyclic carbonates and related organic compounds from CO2 as building blocks has been widely studied, and less attention has been paid to their stereocontrolled process. Therefore, this review focuses on the recent development of enantioselective catalysts for the CO2-mediated formation of chiral organic carbonates.
Catalytic Ability of K- and Co-Promoted Oxo-Re and Oxo-ReMo Nanosized Compositions for Water–Gas Shift Reaction
Authors: Nikolova Dimitrinka , Ivanov Ivan , Vakros John , Gabrovska Margarita , Krstić Jugoslav , Tzvetkov Peter , Petrova Evangeliya , Zarkova Gabriella , Petrova Tanya , Tabakova Tatyana
Published: November 2023

The water–gas shift (WGS) reaction (CO + H2O ↔ CO2 + H2) plays an important role in the hydrogen economy because it is an effective way to reduce the carbon release to net-zero CO2 emissions. The general goal of this research is to develop nanosized oxo-rhenium catalyst formulations promoted by K and Co components for the WGS process. Rhenium, as a low-cost catalyst component, is a good choice compared to platinum group metals. A surface density of 2 Re atoms/nm2 on a γ-Al2O3 support as well as cobalt (3 wt.% CoO) and potassium (5 wt.% K2O) amounts were chosen to match the composition of our own active sour WGS KCoRe catalyst developed some years ago. An initial evaluation of the impact of replacing half of the rhenium with molybdenum, which is more affordable, was also studied. The purpose of this study is to explore the catalytic ability of CoRe, K-CoRe, CoReMo, and K-CoReMo formulations in the WGS reaction and elucidate the effect of a CO/Ar reaction mixture used in an activation–reduction pretreatment to form active catalyst structures. Oxo-K-Co-Re(Mo) entities formed in synthesized samples and their reducibility were analyzed via several physicochemical methods, such as N2 physisorption, PXRD, UV-vis DRS, and H2-TPR. In summary, the selected potassium- and cobalt-promoted Re-containing formulations have potential as catalysts for the classical WGS reaction. The selection of an appropriate procedure for activation–reduction, involving the reducing gas (CO or H2), temperature, and duration, was needed for tuning the K-CoRe catalyst’s high activity for the WGS reaction with structural stability and longevity.
The Inflammasome-Dependent Dysfunction and Death of Retinal Ganglion Cells after Repetitive Intraocular Pressure Spikes
Authors: Spurlock Markus , An Weijun , Reshetnikova Galina , Wen Rong , Wang Hua , Braha Michelle , Solis Gabriela , Kurtenbach Stefan , Galindez Orlando J. , de Rivero Vaccari Juan Pablo , Chou Tsung-Han , Porciatti Vittorio , Shestopalov Valery I.
Published: November 2023

The dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies, where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of a similar intensity and duration failed to induce pathology. The repetitive spOHT induced the rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, and Gasdermin D (GSDMD), and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinogram (PERG) amplitude and a significant loss of RGCs 7 days post-injury. The inactivation of inflammasome complexes in Nlrp1−/−, Casp1−/−, and GsdmD−/− knockout animals significantly suppressed the spOHT-induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death.
Osteopontin Activation and Microcalcification in Venous Grafts Can Be Modulated by Dexamethasone
Authors: McQueen Liam W. , Ladak Shameem S. , Layton Georgia R. , Wadey Kerry , George Sarah J. , Angelini Gianni D. , Murphy Gavin J. , Zakkar Mustafa
Published: November 2023

Background: Osteopontin has been implicated in vascular calcification formation and vein graft intimal hyperplasia, and its expression can be triggered by pro-inflammatory activation of cells. The role of osteopontin and the temporal formation of microcalcification in vein grafts is poorly understood with a lack of understanding of the interaction between haemodynamic changes and the activation of osteopontin. Methods: We used a porcine model of vein interposition grafts, and human long saphenous veins exposed to ex vivo perfusion, to study the activation of osteopontin using polymerase chain reaction, immunostaining, and 18F-sodium fluoride autoradiography. Results: The porcine model showed that osteopontin is active in grafts within 1 week following surgery and demonstrated the presence of microcalcification. A brief pretreatment of long saphenous veins with dexamethasone can suppress osteopontin activation. Prolonged culture of veins after exposure to acute arterial haemodynamics resulted in the formation of microcalcification but this was suppressed by pretreatment with dexamethasone. 18F-sodium fluoride uptake was significantly increased as early as 1 week in both models, and the pretreatment of long saphenous veins with dexamethasone was able to abolish its uptake. Conclusions: Osteopontin is activated in vein grafts and is associated with microcalcification formation. A brief pretreatment of veins ex vivo with dexamethasone can suppress its activation and associated microcalcification.
Impact of Germline Depletion of Bonus on Chromatin State in Drosophila Ovaries
Authors: Godneeva Baira , Fejes Tóth Katalin , Quan Baiyi , Chou Tsui-Fen , Aravin Alexei A.
Published: November 2023

Gene expression is controlled via complex regulatory mechanisms involving transcription factors, chromatin modifications, and chromatin regulatory factors. Histone modifications, such as H3K27me3, H3K9ac, and H3K27ac, play an important role in controlling chromatin accessibility and transcriptional output. In vertebrates, the Transcriptional Intermediary Factor 1 (TIF1) family of proteins play essential roles in transcription, cell differentiation, DNA repair, and mitosis. Our study focused on Bonus, the sole member of the TIF1 family in Drosophila, to investigate its role in organizing epigenetic modifications. Our findings demonstrated that depleting Bonus in ovaries leads to a mild reduction in the H3K27me3 level over transposon regions and alters the distribution of active H3K9ac marks on specific protein-coding genes. Additionally, through mass spectrometry analysis, we identified novel interacting partners of Bonus in ovaries, such as PolQ, providing a comprehensive understanding of the associated molecular pathways. Furthermore, our research revealed Bonus’s interactions with the Polycomb Repressive Complex 2 and its co-purification with select histone acetyltransferases, shedding light on the underlying mechanisms behind these changes in chromatin modifications.
Genomic Profiling and Clinical Outcomes of Targeted Therapies in Adult Patients with Soft Tissue Sarcomas
Authors: Kokkali Stefania , Georgaki Eleni , Mandrakis Georgios , Valverde Claudia , Theocharis Stamatios
Published: November 2023

Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still controversial in patients with sarcoma, given the low mutational burden and the lack of recurrent targetable alterations in most of the sarcoma histotypes. The clinical impact of genomic profiling in STS has not been investigated prospectively. A limited number of retrospective, mainly single-institution, studies have addressed this issue using various NGS technologies and platforms and a variety of criteria to define a genomic alteration as actionable. Despite the detailed reports on the different gene mutations, fusions, or amplifications that were detected, data on the use and efficacy of targeted treatment are very scarce at present. With the exception of gastrointestinal stromal tumors (GISTs), these targeted therapies are administered either through off-label prescription of an approved drug or enrollment in a matched clinical trial. Based mainly on anecdotal reports, the outcome of targeted therapies in the different STS histotypes is discussed. Prospective studies are warranted to assess whether genomic profiling improves the management of STS patients.
Water Vapor Condensation in Nanoparticle Films: Physicochemical Analysis and Application to Rapid Vapor Sensing
Authors: Kano Shinya , Kawakita Jin , Yamashita Shohei , Mekaru Harutaka
Published: November 2023

Nanomaterial-based humidity sensors hold great promise for water vapor detection because of their high sensitivity and fast response/recovery. However, the condensation of water in nanomaterial films remains unclear from a physicochemical perspective. Herein, the condensation of water vapor in silica nanoparticle films was physicochemically analyzed to bridge the abovementioned gap. The morphology of surface-adsorbed water molecules was characterized using infrared absorption spectroscopy and soft X-ray absorption spectroscopy, and the effect of RH on the amount of adsorbed water was observed using a quartz crystal microbalance. The adsorbed water was found to exist in liquid- and ice-like states, which contributed to high and low conductivity, respectively. The large change in film impedance above 80% RH was ascribed to the condensation of water between the nanoparticles. Moreover, RH alteration resulted in a colorimetric change in the film’s interference fringe. The obtained insights were used to construct a portable device with response and recovery times suitable for the real-time monitoring of water vapor. Thus, this study clarifies the structure of water adsorbed on nanomaterial surfaces and, hence, the action mechanism of the corresponding nanoparticle-based sensors, inspiring further research on the application of various nanomaterials to vapor sensing.
Carrot-Induced Systemic Reaction: A Unique Presentation of Pollen-Food Allergy Syndrome in a Young Boy
Authors: Balas Weronika M. , Strzelecka Joanna , Godyńska Aleksandra , Sybilski Adam J.
Published: November 2023

Pollen-food allergy syndrome (PFAS) is a common IgE-mediated allergic condition resulting from cross-reactions between pollen and plant food allergens, primarily those in the PR-10 subfamily. Mostly symptoms are limited to the mouth and throat causing oral allergy syndrome (OAS). Systemic reactions are extremely rare. We report an 11-year-old boy who experienced a unique anaphylactic reaction after consuming raw carrot juice. The patient exhibited symptoms within one minute, including abdominal pain, facial and eyelid swelling, dyspnea, a macular rash, choking sensation and drowsiness. Desloratadine alleviated these symptoms, and as his overall condition improved rapidly, there was no need for adrenaline administration. Carrot-specific IgE levels in the patient’s serum were as follows: Dau c: 40.63 kUA/L and Dau c1: 31.5 kUA/L. He had previously been diagnosed with seasonal allergic rhinoconjunctivitis. The high degree of similarity among allergen components within the PR-10 subfamily contributed to cross-reactivity between birch pollen and carrots. It is important to remember that PFAS can manifest systemically, with symptoms ranging from mild skin itching to potentially fatal consequences. This highlights the need for healthcare professionals to be extra cautious and aware of this possibility, especially since carrots are commonly found in a wide range of dishes and snacks.
Molecular Aspects of MAFLD—New Insights on Pathogenesis and Treatment
Authors: Filipovic Branka , Marjanovic-Haljilji Marija , Mijac Dragana , Lukic Snezana , Kapor Suncica , Kapor Slobodan , Starcevic Ana , Popovic Dusan , Djokovic Aleksandra
Published: November 2023

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications.
Microstructure and Properties of Inconel 718 Coatings with Different Laser Powers on the Surface of 316L Stainless Steel Substrate
Authors: Liu Yu , Zhu Lin , Li Zeyu , Yu Miao , Gao Yali , Liang Hui
Published: November 2023

Laser cladding is a new method to prepare coatings with good quality. Laser power is one of the main factors affecting the quality of laser cladding coatings. An appropriate laser power helps obtain a high-performance laser cladding coating. In order to obtain coatings with good quality, an experiment with different laser powers was designed in this research. Three Inconel 718 coatings with different laser powers were prepared on the surface of a 316L stainless steel substrate. And the effect of different laser powers (1400, 1600, and 1800 W) on the microstructure, phases, and element distribution of coatings (L1–L3) was investigated by SEM, EDS, XRD, and a wear and friction tester. Meanwhile, the microhardness and friction and wear properties of different coatings were analyzed. The results show that the coatings’ phases were the same and composed of γ~(Fe, Ni) solid solution, Ni3Nb, (Nb0.03Ti0.97)Ni3, MCX (M = Cr, Nb, Mo), and so on. The background zones in the L1–L3 coatings were mainly the Fe and Ni elements. The irregular blocks in the coating were rich in Cr, Mo, and Nb, which formed the MCX (M = Cr, Nb, Mo) phase. When laser powers were 1400, 1600, and 1800 W, the average microhardness of the three coatings was 685.6, 604.6, and 551.9 HV0.2, respectively. The L1 coating had the maximum microhardness, 707.5 HV0.2, because the MCX (M = Cr, Nb, Mo)-reinforced phase appeared on the upper part of the coating. The wear rates were 3.65 × 10−5, 2.97 × 10−5, and 6.98 × 10−5 mm3·n−1·m−1. The wear mechanism of the three coatings was abrasive wear and adhesive wear. When the laser power was 1600 W, the coating had the minimum wear rate, which exhibited the best wear resistance. When the laser power was 1600 W, the upper part of the coating to the bonding zone was mainly composed of equiaxed crystals, dendrites, cellular crystals, columnar crystals, and planar crystals. The fine crystals and compounds caused a decrease in wear volume, and they had the most optimal wear resistance.
Effect of Oxygen-Evaporation-Preventative Post-Annealing Gas Conditions on NiO Thin Films
Authors: Kim Hyungmin , Kim Kyunghwan , Hong Jeongsoo
Published: November 2023

In this study, NiO films were fabricated through radio frequency sputtering with various oxygen flow rates and processed via rapid thermal annealing under Ar, O2, and N2 atmospheres. The electrical, optical, and crystallographic properties of the NiO films were influenced by their oxygen content in each film. As the oxygen content, carrier concentration, and resistivity increased, transmittance and mobility decreased. The carrier mobility of the NiO film in the p-type layer of the photodetector requires improvement. Rapid thermal annealing (RTA) has been widely used to improve the crystallinity and mobility of films. However, the reduction in oxygen content during RTA causes a decrease in the carrier concentration and transmittance of NiO films. Regarding the aim of preventing a reduction in oxygen content in the NiO films due to the RTA process, an O2 atmosphere (compared with Ar and N2 atmospheres) was identified as the optimal condition for mobility (3.42 cm2/V·s) and transmittance (50%).
Enhancing Web Application Security through Automated Penetration Testing with Multiple Vulnerability Scanners
Authors: Abdulghaffar Khaled , Elmrabit Nebrase , Yousefi Mehdi
Published: November 2023

Penetration testers have increasingly adopted multiple penetration testing scanners to ensure the robustness of web applications. However, a notable limitation of many scanning techniques is their susceptibility to producing false positives. This paper presents a novel framework designed to automate the operation of multiple Web Application Vulnerability Scanners (WAVS) within a single platform. The framework generates a combined vulnerabilities report using two algorithms: an automation algorithm and a novel combination algorithm that produces comprehensive lists of detected vulnerabilities. The framework leverages the capabilities of two web vulnerability scanners, Arachni and OWASP ZAP. The study begins with an extensive review of the existing scientific literature, focusing on open-source WAVS and exploring the OWASP 2021 guidelines. Following this, the framework development phase addresses the challenge of varying results obtained from different WAVS. This framework’s core objective is to combine the results of multiple WAVS into a consolidated vulnerability report, ultimately improving detection rates and overall security. The study demonstrates that the combined outcomes produced by the proposed framework exhibit greater accuracy compared to individual scanning results obtained from Arachni and OWASP ZAP. In summary, the study reveals that the Union List outperforms individual scanners, particularly regarding recall and F-measure. Consequently, adopting multiple vulnerability scanners is recommended as an effective strategy to bolster vulnerability detection in web applications.
Testate Amoebae (Amphitremida, Arcellinida, Euglyphida) in Sphagnum Bogs: The Dataset from Eastern Fennoscandia
Authors: Ivanovskii Aleksandr , Babeshko Kirill , Chernyshov Viktor , Esaulov Anton , Komarov Aleksandr , Malysheva Elena , Mazei Natalia , Meskhadze Diana , Saldaev Damir , Tsyganov Andrey N. , Mazei Yuri
Published: November 2023

The paper describes a dataset, comprising 236 surface moss samples and 143 testate amoeba taxa. The samples were collected in 11 Sphagnum-dominated bogs during frost-free seasons of 2004, 2007, 2009, 2017, and 2022. For the whole dataset, the sampling effort was sufficient in terms of observed species richness (143 species in total), though a regional species pool is deemed to be discovered incompletely (143 species is its lower 95 % confidence limit using Chao’s estimator). The local community composition demonstrated high heterogeneity in a reduced ordination space. It supports the opinion that the high versatility of bog ecosystems should be taken into account during ecological studies.
Sonographic Aeration Scoring Indicates Disease Severity in Critically Ill Patients with COVID-19
Authors: Marggrander Daniel T. , Simon Philippe , Schröder Tobias , Gill-Schuster Daniel , Mutlak Haitham
Published: November 2023

Aims and Methods: We evaluated an ultrasound score from 0 to 32 points in eight pulmonary regions to monitor critically ill COVID-19 patients. The score was correlated to surrogate parameters of disease severity, i.e., the oxygenation index, respiratory support, mortality, plasma interleukin-6, and WHO and ARDS classifications. Results: A total of 27 patients were repeatedly examined, and 71 examinations were evaluated. Patients with severe COVID-19 scored higher (median 17) than those with moderate disease (median 11, p < 0.01). The score did not differentiate between stages of ARDS as defined by the Berlin criteria (p = 0.1) but could discern ARDS according to the revised ESICM definition (p = 0.002). Non-survivors had higher ultrasound scores than survivors (median 18.5 vs. 14, p = 0.04). The score correlated to the oxygenation index (ρ = −0.56, p = 0.03), and changes in the score between examinations correlated to changes in oxygenation (ρ = −0.41, p = 0.16). The correlation between the score and interleukin-6 was ρ = 0.35 (p < 0.001). The interrater reliability for the score was ICC = 0.87 (p < 0.001). Conclusions: The ultrasound score is a reliable tool that might help monitor disease severity and may help stratify the risk of mortality.
Evaluation of the Easy Albumin–Bilirubin Score as a Prognostic Tool for Mortality in Adult Trauma Patients in the Intensive Care Unit: A Retrospective Study
Authors: Kuo Pao-Jen , Rau Cheng-Shyuan , Tsai Ching-Hua , Chou Sheng-En , Su Wei-Ti , Hsu Shiun-Yuan , Hsieh Ching-Hua
Published: November 2023

The easy albumin–bilirubin (EZ–ALBI) score is derived using the following equation: total bilirubin (mg/dL) − 9 × albumin (g/dL). This study aimed to determine whether the EZ–ALBI score predicted mortality risk in adult trauma patients in an intensive care unit (ICU). Data from a hospital’s trauma database were retrospectively evaluated for 1083 adult trauma ICU patients (139 deaths and 944 survivors) between 1 January 2016 and 31 December 2021. Patients were classified based on the ideal EZ–ALBI cut-off of −26.5, which was determined via receiver operating characteristic curve analysis. The deceased patients’ EZ–ALBI scores were higher than those of the surviving patients (−26.8 ± 6.5 vs. −30.3 ± 5.9, p = 0.001). Multivariate logistic analysis revealed that, in addition to age, the presence of end-stage renal disease, Glasgow Coma Scale scores, and injury severity scores, the EZ–ALBI score is an independent risk factor for mortality (odds ratio (OR), 1.10; 95% confidence interval (CI): 1.06–1.14; p = 0.001)). Compared with patients with EZ–ALBI scores < −26.5, those with scores ≥ −26.5 had a 2.1-fold higher adjusted mortality rate (adjusted OR, 2.14; 95% CI: 1.43–3.19, p = 0.001). In conclusion, the EZ–ALBI score is a substantial and independent predictor of mortality and can be screened to stratify mortality risk in adult trauma ICU patients.
Cancer Diagnosis through Contour Visualization of Gene Expression Leveraging Deep Learning Techniques
Authors: Venkatesan Vinoth Kumar , Kuppusamy Murugesan Karthick Raghunath , Chandrasekaran Kaladevi Amarakundhi , Thyluru Ramakrishna Mahesh , Khan Surbhi Bhatia , Almusharraf Ahlam , Albuali Abdullah
Published: November 2023

Prompt diagnostics and appropriate cancer therapy necessitate the use of gene expression databases. The integration of analytical methods can enhance detection precision by capturing intricate patterns and subtle connections in the data. This study proposes a diagnostic-integrated approach combining Empirical Bayes Harmonization (EBS), Jensen–Shannon Divergence (JSD), deep learning, and contour mathematics for cancer detection using gene expression data. EBS preprocesses the gene expression data, while JSD measures the distributional differences between cancerous and non-cancerous samples, providing invaluable insights into gene expression patterns. Deep learning (DL) models are employed for automatic deep feature extraction and to discern complex patterns from the data. Contour mathematics is applied to visualize decision boundaries and regions in the high-dimensional feature space. JSD imparts significant information to the deep learning model, directing it to concentrate on pertinent features associated with cancerous samples. Contour visualization elucidates the model’s decision-making process, bolstering interpretability. The amalgamation of JSD, deep learning, and contour mathematics in gene expression dataset analysis diagnostics presents a promising pathway for precise cancer detection. This method taps into the prowess of deep learning for feature extraction while employing JSD to pinpoint distributional differences and contour mathematics for visual elucidation. The outcomes underscore its potential as a formidable instrument for cancer detection, furnishing crucial insights for timely diagnostics and tailor-made treatment strategies.