bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of the Production Technology of a Bent Component
Authors: Čada Radek , Pektor Tomáš
Published: December 2023

This paper concerns the design of the technology for the production of the part by bending and also the design of the forming tool for a small number of pieces of the produced part. The part in question was the oscillating tool blade to cut soft materials. The aim was to design economically advantageous technology to produce this blade without spot welding from two parts, preferably from one semi-finished product. A suitable material for the part and its new shape were designed. Calculations were made for the smallest recommended internal bending radius, the largest allowable bending radius, the smallest length of the bending arm, and the angle of springback after bending. The component’s shape and a suitable blank were determined. A low-cost bending tool was designed. Dynaform simulations were used to analyse deformation, material thickness after bending, and formability. Analyses showed that the designed bending manufacturing process is safe. The bending tool and then the cutting blade test pieces were produced to verify the tool’s functionality. The procedure for designing the manufacturing process and the forming tool presented in the paper can be applied in cases where it is necessary to design a suitable technology to produce a small number of parts by forming to achieve a minimum cost per piece of the manufactured part.
Assessing Antithetic Sampling for Approximating Shapley, Banzhaf, and Owen Values
Authors: Staudacher Jochen , Pollmann Tim
Published: December 2023

Computing Shapley values for large cooperative games is an NP-hard problem. For practical applications, stochastic approximation via permutation sampling is widely used. In the context of machine learning applications of the Shapley value, the concept of antithetic sampling has become popular. The idea is to employ the reverse permutation of a sample in order to reduce variance and accelerate convergence of the algorithm. We study this approach for the Shapley and Banzhaf values, as well as for the Owen value which is a solution concept for games with precoalitions. We combine antithetic samples with established stratified sampling algorithms. Finally, we evaluate the performance of these algorithms on four different types of cooperative games.
Role of MOB4 in Cell Proliferation and Neurogenesis
Authors: Santos Inês B. , Garrido-Maraver Juan , Gonçalves Carolina , Oliveira Bruna I. , Tavares Álvaro A.
Published: December 2023

Signaling pathways that integrate a large set of inputs (both extra- and intracellular) to control cell proliferation are essential during both development and adult stages to guarantee organism homeostasis. Mobs are small adaptor proteins that participate in several of these signaling pathways. Here, we review recent advances unravelling Mob4 cellular functions, a highly conserved non-catalytic protein, that plays a diversity of roles in cell proliferation, sperm cell differentiation and is simultaneously involved in synapse formation and neural development. In addition, the gene is often overexpressed in a large diversity of tumors and is linked to poor clinical outcomes. Nevertheless, Mob4 molecular functions remain poorly defined, although it integrates the core structure of STRIPAK, a kinase/phosphatase protein complex, that can act upstream of the Hippo pathway. In this review we focus on the recent findings of Mob4 functions, that have begun to clarify its critical role on cell proliferation and the development of tissues and individuals.
Versatility of Glutathione Transferase Proteins
Authors: Mannervik Bengt
Published: December 2023

For more than 60 years, glutathione transferases (GSTs) have attracted attention, but the research field of the GSTome [...]
A Method for Using Cell-Penetrating Peptides for Loading Plasmid DNA into Secreted Extracellular Vesicles
Authors: Nebogatova Jekaterina , Härk Heleri Heike , Puskar Anett , Porosk Ly , Guazzi Paolo , Dowaidar Moataz , Langel Ülo , Kurrikoff Kaido
Published: December 2023

The low bioavailability and high toxicity of plasmid DNA (pDNA)-based therapeutics pose challenges for their in vivo application. Extracellular vesicles (EVs) have great potential to overcome these limitations, as they are biocompatible native cargo carriers. Various methods for loading pDNA into EVs, including electroporation, sonication, and co-incubation, have been previously investigated, but their success has been questionable. In this study, we report a unique method for loading EVs with pDNA through transient transfection using cell-penetrating peptides (CPPs). With this method, we found a 104-fold increase in the expression levels of the luciferase reporter protein in recipient cells compared to the untreated cells. These data point to the high transfection efficacy and bioavailability of the delivered encapsulated nucleic acid. Furthermore, the in vivo experimental data indicate that the use of pDNA-loaded EVs as native delivery vehicles reduces the toxic effects associated with traditional nucleic acid (NA) delivery and treatment.
Effects of Virtual Reality Cognitive Training on Neuroplasticity: A Quasi-Randomized Clinical Trial in Patients with Stroke
Authors: Gangemi Antonio , De Luca Rosaria , Fabio Rosa Angela , Lauria Paola , Rifici Carmela , Pollicino Patrizia , Marra Angela , Olivo Antonella , Quartarone Angelo , Calabrò Rocco Salvatore
Published: December 2023

Cognitive Rehabilitation (CR) is a therapeutic approach designed to improve cognitive functioning after a brain injury, including stroke. Two major categories of techniques, namely traditional and advanced (including virtual reality—VR), are widely used in CR for patients with various neurological disorders. More objective outcome measures are needed to better investigate cognitive recovery after a stroke. In the last ten years, the application of electroencephalography (EEG) as a non-invasive and portable neuroimaging method has been explored to extract the hallmarks of neuroplasticity induced by VR rehabilitation approaches, particularly within the chronic stroke population. The aim of this study is to investigate the neurophysiological effects of CR conducted in a virtual environment using the VRRS device. Thirty patients with moderate-to-severe ischemic stroke in the chronic phase (at least 6 months after the event), with a mean age of 58.13 (±8.33) for the experimental group and 57.33 (±11.06) for the control group, were enrolled. They were divided into two groups: an experimental group and a control group, receiving neurocognitive stimulation using VR and the same amount of conventional neurorehabilitation, respectively. To study neuroplasticity changes after the training, we focused on the power band spectra of theta, alpha, and beta EEG rhythms in both groups. We observed that when VR technology was employed to amplify the effects of treatments on cognitive recovery, significant EEG-related neural improvements were detected in the primary motor circuit in terms of power spectral density and time-frequency domains. Indeed, EEG analysis suggested that VR resulted in a significant increase in both the alpha band power in the occipital areas and the beta band power in the frontal areas, while no significant variations were observed in the theta band power. Our data suggest the potential effectiveness of a VR-based rehabilitation approach in promoting neuroplastic changes even in the chronic phase of ischemic stroke.
Cushing’s Disease: Long-Term Effectiveness and Safety of Osilodrostat in a Polish Group of Patients with Persistent Hypercortisolemia in the Experience of a Single Center
Authors: Dzialach Lukasz , Sobolewska Joanna , Respondek Wioleta , Szamotulska Katarzyna , Witek Przemysław
Published: December 2023

Osilodrostat is a potent oral steroidogenesis inhibitor that has emerged as the new medical agent for patients with Cushing’s disease (CD) requiring long-term medical therapy for hypercortisolemia control. Its efficacy and safety have been assessed in clinical trials; however, real-world evidence is still scarce. This study aimed to investigate the long-term treatment (156 weeks) clinical and biochemical effect of osilodrostat in six patients with CD at a single center in Poland, initially participating in the LINC4 study. At week 36, all six patients met the key secondary endpoint of the LINC4 trial, achieving normalization of median urinary free cortisol. Osilodrostat treatment allowed for complete disease control in all patients and none of the patients was excluded due to the lack of treatment effectiveness in 156 weeks of follow-up. All patients demonstrated significant improvement from baseline on most metabolic and cardiovascular parameters, which was most evident at week 36 and sustained throughout the study period. This study supports and strengthens the role of osilodrostat as an effective long-term medical treatment in patients with CD. We also present three patient case histories in detail to highlight the clinical situations that endocrinologists might face during osilodrostat therapy.
Inflammatory Pathways in Overweight and Obese Persons as a Potential Mechanism for Cognitive Impairment and Earlier Onset Alzeihmer’s Dementia in the General Population: A Narrative Review
Authors: Costache Alexandru Dan , Ignat Bogdan Emilian , Grosu Cristina , Mastaleru Alexandra , Abdulan Irina , Oancea Andra , Roca Mihai , Leon Maria Magdalena , Badescu Minerva Codruta , Luca Stefana , Jigoranu Alexandru Raul , Chetran Adriana , Mitu Ovidiu , Costache Irina Iuliana , Mitu Florin
Published: December 2023

The overweight status or obesity can be confirmed through classical methods such as the body mass index (BMI) and the waist-to-hip ratio (WHR). Apart from metabolic issues such as atherosclerosis, liver steatosis, or diabetes mellitus, long-term obesity or overweight status can pose a risk for cardiovascular and neurovascular complications. While some acute adverse events like coronary syndromes of strokes are well-documented to be linked to an increased body mass, there are also chronic processes that, due to their silent onset and evolution, are underdiagnosed and not as thoroughly studied. Through this review, we aimed to collect all relevant data with regard to the long-term impact of obesity on cognitive function in all ages and its correlation with an earlier onset of dementia such as Alzheimer’s disease (AD). The exact mechanisms through which a decline in cognitive functions occurs in overweight or obese persons are still being discussed. A combination of factors has been acknowledged as potential triggers, such as a sedentary lifestyle and stress, as well as a genetic predisposition, for example, the apolipoprotein E (ApoE) alleles in AD. Most research highlights the impact of vascular dysfunction and systemic inflammation on the nervous system in patients with obesity and the subsequent neurological changes. Obesity during the early to mid-ages leads to an earlier onset of cognitive dysfunction in various forms. Also, lifestyle intervention can reverse cognitive dysfunction, especially dieting, to encourage weight loss.
Interruption of Lymph Flow Worsens the Skin Inflammation Caused by Saprophytic Staphylococcus epidermidis
Authors: Cąkała-Jakimowicz Marta , Domaszewska-Szostek Anna , Puzianowska-Kuznicka Monika
Published: December 2023

Lymphedema is often complicated by chronic inflammation, leading to fibrosis, fat deposition, and inhibition of lymphangiogenesis. This study aimed to verify whether lymphedema itself or together with commensal bacterial flora infection contributes to the severity of local inflammation. Edema was induced by interruption of the lymph flow in the rat’s hind limb. Immune cell infiltrates were examined by flow cytometry and immunohistochemistry. Nine-day edema alone did not affect immune cell content in the skin but resulted in a decrease in CD4+ T helper lymphocytes and monocytes in the draining popliteal lymph nodes. In turn, local saprophytic Staphylococcus epidermidis infection of the edematous limb resulted in dense infiltrates of CD68+ macrophages and monocytes, MHC class II antigen-presenting cells, CD90+ stem cells, thymocytes, and immature B cells in the skin, accompanied by a simultaneous reduction in density of CD4+ T helper lymphocytes and monocytes, OX62+ dendritic cells, CD68+ macrophages and monocytes, HiS48+ granulocytes, CD90+ stem cells, thymocytes, and immature B cells in the draining popliteal lymph nodes. These results indicate that the combination of edema and saprophytic bacteria infection induces severe inflammation in the peripheral tissues and results in a delay of antibacterial protection processes in neighboring lymphatic organs.
Enhancing Brain Tumor Classification with Transfer Learning across Multiple Classes: An In-Depth Analysis
Authors: Ahmmed Syed , Podder Prajoy , Mondal M. , Rahman S , Kannan Somasundar , Hasan Md , Rohan Ali , Prosvirin Alexander
Published: December 2023

This study focuses on leveraging data-driven techniques to diagnose brain tumors through magnetic resonance imaging (MRI) images. Utilizing the rule of deep learning (DL), we introduce and fine-tune two robust frameworks, ResNet 50 and Inception V3, specifically designed for the classification of brain MRI images. Building upon the previous success of ResNet 50 and Inception V3 in classifying other medical imaging datasets, our investigation encompasses datasets with distinct characteristics, including one with four classes and another with two. The primary contribution of our research lies in the meticulous curation of these paired datasets. We have also integrated essential techniques, including Early Stopping and ReduceLROnPlateau, to refine the model through hyperparameter optimization. This involved adding extra layers, experimenting with various loss functions and learning rates, and incorporating dropout layers and regularization to ensure model convergence in predictions. Furthermore, strategic enhancements, such as customized pooling and regularization layers, have significantly elevated the accuracy of our models, resulting in remarkable classification accuracy. Notably, the pairing of ResNet 50 with the Nadam optimizer yields extraordinary accuracy rates, reaching 99.34% for gliomas, 93.52% for meningiomas, 98.68% for non-tumorous images, and 97.70% for pituitary tumors. These results underscore the transformative potential of our custom-made approach, achieving an aggregate testing accuracy of 97.68% for these four distinct classes. In a two-class dataset, Resnet 50 with the Adam optimizer excels, demonstrating better precision, recall, F1 score, and an overall accuracy of 99.84%. Moreover, it attains perfect per-class accuracy of 99.62% for ‘Tumor Positive’ and 100% for ‘Tumor Negative’, underscoring a remarkable advancement in the realm of brain tumor categorization. This research underscores the innovative possibilities of DL models and our specialized optimization methods in the domain of diagnosing brain cancer from MRI images.
Lafora Disease: A Case Report and Evolving Treatment Advancements
Authors: Ferrari Aggradi Carola Rita , Rimoldi Martina , Romagnoli Gloria , Velardo Daniele , Meneri Megi , Iacobucci Davide , Ripolone Michela , Napoli Laura , Ciscato Patrizia , Moggio Maurizio , Comi Giacomo Pietro , Ronchi Dario , Corti Stefania , Abati Elena
Published: December 2023

Lafora disease is a rare genetic disorder characterized by a disruption in glycogen metabolism. It manifests as progressive myoclonus epilepsy and cognitive decline during adolescence. Pathognomonic is the presence of abnormal glycogen aggregates that, over time, produce large inclusions (Lafora bodies) in various tissues. This study aims to describe the clinical and histopathological aspects of a novel Lafora disease patient, and to provide an update on the therapeutical advancements for this disorder. A 20-year-old Libyan boy presented with generalized tonic–clonic seizures, sporadic muscular jerks, eyelid spasms, and mental impairment. Electroencephalography showed multiple discharges across both brain hemispheres. Brain magnetic resonance imaging was unremarkable. Muscle biopsy showed increased lipid content and a very mild increase of intermyofibrillar glycogen, without the polyglucosan accumulation typically observed in Lafora bodies. Despite undergoing three lines of antiepileptic treatment, the patient’s condition showed minimal to no improvement. We identified the homozygous variant c.137G>A, p.(Cys46Tyr), in the EPM2B/NHLRC1 gene, confirming the diagnosis of Lafora disease. To our knowledge, the presence of lipid aggregates without Lafora bodies is atypical. Lafora disease should be considered during the differential diagnosis of progressive, myoclonic, and refractory epilepsies in both children and young adults, especially when accompanied by cognitive decline. Although there are no effective therapies yet, the development of promising new strategies prompts the need for an early and accurate diagnosis.
Neurostimulating Architecture Applied in the Design of Educational Centers and Early Cognitive Development in the District of Villa El Salvador, Lima
Authors: Esenarro Doris , Ccalla Jimena , Raymundo Vanessa , Castañeda Lorena , Davila Susana
Published: December 2023

The objective of this research is to propose the implementation of neurostimulating architecture strategies for the design of early childhood educational centers. These strategies could be relevant for their implementation in rapidly growing urban areas in Peru, where many children lack access to early education. There has been an increase of 4.40% in the dropout rate at this educational level in recent years, and it has been observed that classrooms and educational facilities are not adequately prepared to accommodate the activities of this educational level. Likewise, the difficulty in accessing simple architectural design strategies that enhance cognitive development in children is concerning, especially when infants in early childhood have a natural capacity to acquire new knowledge, which, if not stimulated, could impact their adult lives. The research methodology adopts a mixed approach, analyzing two educational centers in the Villa El Salvador district to evaluate their current conditions in relation to neurostimulating architecture indicators. Interviews with specialists, questionnaires for the study subjects, and an observation guide were also used. This comprehensive approach allows for a better analysis and interpretation of the results. As a result, accessible design archetypes based on nine neurostimulating architecture indicators (illumination, green areas, shape, size, layout, accessibility, scale, colors, materiality) were obtained, and these were applied in an architectural design proposal for an early education center. In conclusion, the application of neurostimulating architecture as a strategy in the design of early childhood education centers has the potential to improve learning and enhance early cognitive development.
Research on the Mechanical Performance of a Mountainous Long-Span Steel Truss Arch Bridge with High and Low Arch Seats
Authors: Tan Yao , Shi Junfeng , Liu Peng , Tao Jun , Zhao Yueyue
Published: December 2023

The Loushui River Bridge is a mountainous long-span steel truss arch bridge with high and low arch seats. The design and construction of the bridge follow the principle of minimizing environmental damage and promoting sustainable development. In this article, the mechanical performance of this bridge is investigated experimentally and numerically at both the construction and operation stages. A series of validated finite element models were established for linear and nonlinear analyses by introducing geometric imperfections, geometric nonlinearities, and material nonlinearities. Then, several optimized models based on different types of design are compared with the original structure. The results indicate that the stability of the asymmetric bridge met the design requirements in both the construction and operation stages. However, the lateral stability and stiffness of the asymmetric bridge are weak due to the wind hazard that occurred in its mountain ravine. The out-of-plane instability from the short half-arch is the dominant failure mode, and the weakest area is where the arch ribs intersect with the bridge deck. It can be solved by adding more cross bracings without affecting the clearance above the bridge deck or by improving the material intensity of the arch.
Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy
Authors: Wetz Christoph , Ruhwedel Tristan , Schatka Imke , Grabowski Jane , Jann Henning , Metzger Giulia , Galler Markus , Amthauer Holger , Rogasch Julian M. M.
Published: December 2023

Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.
Androgen Receptor/AP-1 Activates UGT2B15 Transcription to Promote Esophageal Squamous Cell Carcinoma Invasion
Authors: Cai Jiahui , Huang Furong , Gao Wenyan , Gong Tongyang , Chen Hongyan , Liu Zhihua
Published: December 2023

Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy with poor prognosis. Interestingly, ESCC is strongly characterized by a male-predominant propensity. Our previous study showed that androgen receptor (AR) orchestrated a transcriptional repression program to promote ESCC growth, but it remains unclear whether AR can also activate oncogenic signaling during ESCC progression. In this study, by analyzing our previous AR cistromes and androgen-regulated transcriptomes, we identified uridine diphosphate glucuronosyltransferase family 2 member B15 (UGT2B15) as a bona fide target gene of AR. Mechanistically, AP-1 cofactors played important and collaborative roles in AR-mediated UGT2B15 upregulation. Functional studies have revealed that UGT2B15 promoted invasiveness in vitro and lymph node metastasis in vivo. UGT2B15 was partially responsible for the AR-induced invasive phenotype in ESCC cells. Importantly, simultaneous blocking of AP-1 and AR resulted in stronger inhibition of cell invasiveness compared to inhibiting AP-1 or AR alone. In conclusion, our study reveals the molecular mechanisms underlying the AR-driven ESCC invasion and suggests that the AR/AP1/UGT2B15 transcriptional axis can be potentially targeted in suppressing metastasis in male ESCC patients.
Practical Challenges of DBT-Guided VABB: Harms and Benefits, from Literature to Clinical Experience
Authors: Tari Daniele Ugo , De Lucia Davide Raffaele , Santarsiere Marika , Santonastaso Rosalinda , Pinto Fabio
Published: December 2023

Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we retrospectively analyzed the DBT-guided VABBs performed from 2019 to 2022 at our department. Descriptive statistics, Pearson’s correlation and χ2 test were used to compare distributions of age, breast density (BD) and early performance measures including histopathology. We used kappa statistics to evaluate the agreement between histological assessment and diagnosis. Finally, we compared our experience to the literature to provide indications for clinical practice. We included 85 women aged 41–84 years old. We identified 37 breast cancers (BC), 26 stage 0 and 11 stage IA. 67.5% of BC was diagnosed in women with high BD. The agreement between VABB and surgery was 0.92 (k value, 95% CI: 0.76–1.08). We found a statistically significant inverse correlation between age and BD. The post-procedural clip was correctly positioned in 88.2%. The post-procedural hematoma rate was 14.1%. No infection or hemorrhage were recorded. When executed correctly, DBT-guided VABB represents a safe and minimally invasive technique with high histopathological concordance, for detecting nonpalpable lesions without ultrasound correlation.
Cardiac Arrhythmias in Patients Treated for Lung Cancer: A Review
Authors: Hawryszko Maja , Sławiński Grzegorz , Tomasik Bartłomiej , Lewicka Ewa
Published: December 2023

Cardio-oncology currently faces one of the greatest challenges in the field of health care. The main goal of this discipline is to ensure that patients treated for cancer do not suffer or die from cardiovascular disease. The number of studies on the mechanisms of heart injury during cancer treatment is constantly increasing. However, there is insufficient data on heart rhythm disorders that may result from this treatment. This issue seems to be particularly important in patients with lung cancer, in whom anticancer therapy, especially radiotherapy, may contribute to the onset of cardiac arrhythmias. The observed relationship between cardiac dosimetry and radiotherapy-induced cardiotoxicity in lung cancer treatment may explain the increased mortality from cardiovascular causes in patients after chest irradiation. Further research is essential to elucidate the role of cardiac arrhythmias in this context. Conversely, recent reports have highlighted the application of stereotactic arrhythmia radioablation (STAR) in the treatment of ventricular tachycardia. This review of available studies on the epidemiology, pathogenesis, diagnosis, and treatment of arrhythmias in patients treated for lung cancer aims to draw attention to the need for regular cardiological monitoring in this group of patients. Improving cardiac care for patients with lung cancer has the potential to enhance their overall therapeutic outcomes.
Gastro-Esophageal Junction Precancerosis: Histological Diagnostic Approach and Pathogenetic Insights
Authors: Giacometti Cinzia , Gusella Anna , Cassaro Mauro
Published: December 2023

Barrett’s esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal metaplasia within the esophagus. Chronic gastro-esophageal reflux disease (GERD) is a significant risk factor for adenocarcinoma of the esophagus, as intestinal metaplasia can develop due to GERD. The development of adenocarcinomas related to BE progresses in sequence from inflammation to metaplasia, dysplasia, and ultimately carcinoma. In the presence of GERD, the squamous epithelium changes to columnar epithelium, which initially lacks goblet cells, but later develops goblet cell metaplasia and eventually dysplasia. The accumulation of multiple genetic and epigenetic alterations leads to the development and progression of dysplasia. The diagnosis of BE requires the identification of intestinal metaplasia on histologic examination, which has thus become an essential tool both in the diagnosis and in the assessment of dysplasia’s presence and degree. The histologic diagnosis of BE dysplasia can be challenging due to sampling error, pathologists’ experience, interobserver variation, and difficulty in histologic interpretation: all these problems complicate patient management. The development and progression of Barrett’s esophagus (BE) depend on various molecular events that involve changes in cell-cycle regulatory genes, apoptosis, cell signaling, and adhesion pathways. In advanced stages, there are widespread genomic abnormalities with losses and gains in chromosome function, and DNA instability. This review aims to provide an updated and comprehensible diagnostic approach to BE based on the most recent guidelines available in the literature, and an overview of the pathogenetic and molecular mechanisms of its development.
Recent Applications of Flavin-Dependent Monooxygenases in Biosynthesis, Pharmaceutical Development, and Environmental Science
Authors: Guan Yuze , Chen Xi
Published: December 2023

Flavin-dependent monooxygenases (FMOs) have raised substantial interest as catalysts in monooxygenation reactions, impacting diverse fields such as drug metabolism, environmental studies, and natural product synthesis. Their application in biocatalysis boasts several advantages over conventional chemical catalysis, such as heightened selectivity, safety, sustainability, and eco-friendliness. In the realm of biomedicine, FMOs are pivotal in antibiotic research, significantly influencing the behavior of natural products, antimicrobial agents, and the pathways critical to drug synthesis They are also underscored as potential pharmaceutical targets, pivotal in opposing disease progression and viable for therapeutic intervention. Additionally, FMOs play a substantial role in environmental science, especially in pesticide processing and in preserving plant vitality. Their involvement in the biosynthesis of compounds like polyethers, tropolones, and ω-hydroxy fatty acids, with remarkable regio- and stereoselectivity, renders them indispensable in drug discovery and development. As our comprehension of FMOs’ catalytic mechanisms and structures advances, through the use of cutting-edge biotechnologies like computational design and directed evolution, FMOs are poised to occupy an increasingly significant role in both scientific exploration and industrial applications.
FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity
Authors: Fiorillo Marco , Ricci Elena , Fava Mariarosa , Longobucco Camilla , Sotgia Federica , Rizza Pietro , Lanzino Marilena , Bonofiglio Daniela , Conforti Francesca Luisa , Catalano Stefania , Barone Ines , Morelli Catia , Aquila Saveria , Lisanti Michael P. , Sisci Diego
Published: December 2023

Tamoxifen-resistant breast cancer cells (TamR-BCCs) are characterized by an enhanced metabolic phenotype compared to tamoxifen-sensitive cells. FoxO3a is an important modulator of cell metabolism, and its deregulation has been involved in the acquisition of tamoxifen resistance. Therefore, tetracycline-inducible FoxO3a was overexpressed in TamR-BCCs (TamR/TetOn-AAA), which, together with their control cell line (TamR/TetOn-V), were subjected to seahorse metabolic assays and proteomic analysis. FoxO3a was able to counteract the increased oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) observed in TamR by reducing their energetic activity and glycolytic rate. FoxO3a caused glucose accumulation, very likely by reducing LDH activity and mitigated TamR biosynthetic needs by reducing G6PDH activity and hindering NADPH production via the pentose phosphate pathway (PPP). Proteomic analysis revealed a FoxO3a-dependent marked decrease in the expression of LDH as well as of several enzymes involved in carbohydrate metabolism (e.g., Aldolase A, LDHA and phosphofructokinase) and the analysis of cBioPortal datasets of BC patients evidenced a significant inverse correlation of these proteins and FoxO3a. Interestingly, FoxO3a also increased mitochondrial biogenesis despite reducing mitochondrial functionality by triggering ROS production. Based on these findings, FoxO3a inducing/activating drugs could represent promising tools to be exploited in the management of patients who are refractory to antiestrogen therapy.
Evaluation of Stabilization and Physical–Chemical Properties of CNT Antifreeze Nanofluid Prepared in 50:50 EG/Water by Modified Strategy
Authors: Yadav Priyanka , Gupta Shipra Mital , Sharma Surendra Kumar
Published: December 2023

This article proposes a better alternative method to prepare CNT antifreeze nanofluid in EG/water by modifying the conventional method that requires long hours of sonication. Sonicating a sample for long hours is time and energy consuming and may deform the structure of CNT. In the modified method, the nanofluid preparation was carried out by dispersion of CNT in EG via sonication followed by adding water and again sonication. The study shows that nanofluid could be prepared in less sonication time of 1.5 h compared to the 5 h required in the conventional method. FTIR spectroscopy revealed that interaction of EG with CNT occurs via trans conformation resulting in greater stabilization and better interaction of nanofluid prepared by this method (85 days) as compared to nanofluid prepared by the conventional method (50 days). The nanofluid prepared by this method has better physical–chemical properties compared to nanofluid prepared by the conventional method. The nanofluid prepared by this method showed higher stability and better physical–chemical properties at a lower sonication time. Hence it is a more effective and cost efficient technique for preparing CNT (EG/water) nanofluid.
Motivations for Adolescent COVID-19 Vaccination: A Comparative Study of Adolescent and Caregiver Perspectives in Germany
Authors: Rothoeft Tobias , Brinkmann Folke , Maier Christoph , Selzer Dominik , Dings Christiane , Kuehn Anna , Möhler Eva , Grote Hanna , Nonnenmacher Alexandra , Wenning Markus , Zemlin Michael , Richter Ulf , Lehr Thorsten , Lücke Thomas
Published: December 2023

Given the crucial role of vaccination in halting the COVID-19 pandemic, it is imperative to understand the factors that motivate adolescents to get vaccinated. We surveyed adolescents and their accompanying guardians scheduled to receive a COVID-19 vaccination (Comirnaty) in an urban region in Germany in mid-2021 regarding their motivation for getting vaccinated and collected data on their sociodemographic characteristics, medical history, vaccination status, and any history of COVID-19 infection in the family. We also queried information strategies related to the SARS-CoV-2 pandemic. Motivations for getting vaccinated were similar among adolescents and their parents. The primary reasons for vaccination were protection against SARS-CoV-2-related illness and gaining access to leisure facilities. This was not influenced by gender, health status, migration background, or the presence of chronic or acute diseases. The percentage of parents who had received SARS-CoV-2 immunization and the proportion of parents with a high level of education were higher among study participants than in the general population. Adolescents were especially willing to be vaccinated if they came from a better educational environment and had a high vaccination rate in the family. Emphasizing the importance of vaccination among all segments of the population and removing barriers to vaccines may lead to an ameliorated acceptance of COVID-19 vaccines.
Interconnected Pathways: Postural Stability and Vocabulary Skills in Preschool-Aged Children
Authors: Calignano Giulia , Lettere Giorgia , Leo Irene , Maritan Francesca , Mattera Laura , Granata Patrizia , Lucangeli Daniela , Valenza Eloisa
Published: December 2023

Previous research has highlighted an interplay between postural abilities and linguistic skills during infancy. However, this relationship could undergo further radical transformations in other periods of development. This current study explored a plausible network of relationships among postural abilities and vocabulary skills in a substantial cohort (N = 222) of preschoolers aged between 2 and 5 years—a developmental phase critical for refining both language and motor competencies. Here, postural stability was measured in terms of balance duration and accuracy, alongside an assessment of comprehension and expressive vocabulary skills. Employing a diverse set of techniques, i.e., data and missing data visualization and multilevel regression analysis, task complexity and age emerged as crucial factors explaining our data. In addition, network analysis indicates that language production plays a central role within postural and language interdomain networks. The resulting discussion focuses on the useful implications of this study for the assessment of typical preschool development, which would benefit from tailored methodological inspections guided by developmental theories that are framed in inter-domain approaches.
Effect of the Molybdenum Content on Wear and Corrosion Behavior of Fe-B-Based Surface-Alloyed Layer
Authors: Kocaman Engin
Published: December 2023

In this study, Fe-Mo-B-based hardfacing electrodes containing different amounts of Mo were coated on an AISI 1020 steel substrate using the electric arc welding method. The findings show that molybdenum is highly effective on the microstructure and minor changes in the coating composition affect the phases and morphological properties. In the hardness tests, an increase of 73% was achieved in the Fe14Mo2B4-based hardfacing coating, compared to the base material, and a 30% increase was achieved, compared to the Fe16B4-based coating. The highest hardness value was measured as 56.4 HRC and the highest phase hardness was measured as 3228 HV in the FeMo2B4 phase. The lowest wear rate was measured in the Fe14Mo2B4-based coating. The wear rate of the Fe14Mo2B4-based coating was 8.1 times lower than that of the substrate material and 4.7 times lower than that of the Fe16B4-based coating. According to corrosion test results, the highest corrosion resistance was obtained in the Fe16B4-based coating. The current density value of the Fe16B4-based coating was measured to be 13.6 times lower than that of the substrate material.
Development of a Real-Time Boron Concentration Monitoring Technique for Plasma Doping Implantation
Authors: Chai Su-Young , Choa Sung-Hoon
Published: December 2023

Plasma doping (PLAD) technology is widely used in the semiconductor industry. One of the problems associated with PLAD is precise dosage control and monitoring during the doping process. Excessive boron doping into the n-type poly gate will affect the p-MOSFET threshold voltage. In this study, we develop a novel method for the real-time monitoring of the boron concentration as it penetrates into an oxide film. We attempted to determine whether the real-time monitoring of the boron concentration can be replaced by measuring the thickness of the damaged layer remaining after plasma doping and a cleaning process, since the thickness of the damaged layer can be measured relatively easily in real time by means of ellipsometry. It is found that as the plasma doping energy is increased, the boron concentration increases linearly, with a strong correlation (R2 = 0.98) between the plasma doping energy and the boron concentration. Moreover, there is a close relationship between the plasma doping energy and the thickness of the damaged layer. As the doping energy is increased, the thickness of the damaged layer also increases linearly. We also find a close correlation (R2 = 0.92) between the change in the thickness of the damaged layer and the p-MOSFET threshold voltage. In summary, there are very good correlations between the plasma doping energy and the concentration of boron, the doping energy and the thickness of the damaged layer, and the thickness of the damaged layer and the threshold voltage. It is proven that the concentration of boron penetrating into the oxide layer can be monitored by measuring the thickness of the damaged layer in real time.
Factors Predictive of Positive Lymph Nodes for Breast Cancer
Authors: Elleson Kelly M. , Englander Katherine , Gallagher Julia , Chintapally Neha , Sun Weihong , Whiting Junmin , Mallory Melissa , Kiluk John , Hoover Susan , Khakpour Nazanin , Czerniecki Brian , Laronga Christine , Lee Marie Catherine
Published: December 2023

Background: Axillary node status is an important prognostic factor in breast cancer. The primary aim was to evaluate tumor size and other characteristics relative to axillary disease. Materials and Methods: Single institution retrospective chart review of stage I-III breast cancer patients collected demographic and clinical/pathologic data from 1998–2019. Student’s t-test, Chi-squared test (or Fisher exact test if applicable), and logistic regression models were used for testing the association of pN+ to predictive variables. Results: Of 728 patients (mean age 59 yrs) with mean follow up of 50 months, 86% were estrogen receptor +, 10% Her2+, 78% ER+HER2−negative, and 10% triple-negative. In total, 351/728 (48.2%) were pN+ and mean tumor size was larger in pN+ cases compared to pN− cases (mean = 27.7 mm versus 15.5 mm) (p < 0.001). By univariate analysis, pN+ was associated with lymphovascular invasion (LVI), higher grade, Her2, and histology (p < 0.005). Tumor-to-nipple distance was shorter in pN+ compared to pN− (45 mm v. 62 mm; p< 0.001). Age < 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were associated with 3+ positive nodes (p < 0.05). Conclusions: Larger tumor size and shorter tumor-nipple distance were associated with higher lymph node positivity. Age less than 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were all associated with 3+ positive lymph nodes.
The Effects of Antimicrobial Photodynamic Therapy Used to Sterilize Carious Dentin on Rat Dental Pulp Tissue
Authors: Takahashi Tenyu , Sato Fumiaki , Shinkai Koichi
Published: December 2023

Antimicrobial photodynamic therapy (aPDT) used to sterilize carious dentin may irritate pulp tissues because of tissue-penetrating laser and singlet oxygen generation. This study aimed to assess the effects of aPDT on rat pulp tissues. A cavity formed in a rat maxillary first molar was treated with aPDT. The combined photosensitizer and laser irradiation conditions in the aPDT groups were as follows: methylene blue and 100 mW for 60 s, brilliant blue (BB) and 100 mW for 60 s, BB and 50 mW for 120 s, and BB and 200 mW for 30 s. Each cavity was treated with an all-in-one adhesive and filled with flowable resin. aPDT was not applied for the control. In each group, the rats were sacrificed on postoperative days 1 and 14, and thin sections of the treated teeth were prepared. Pulp tissue disorganization (PTD), inflammatory cell infiltration (ICI), and tertiary dentin formation (TDF) were evaluated. At 1-day evaluation, there were significant differences between the aPDT group and controls with respect to PTD and ICI (p < 0.01); 14 days later, almost all specimens showed tertiary dentin formation. The application of aPDT caused reversible damage to the rat pulp, while in the long term, healing occurred with the formation of tertiary dentin.
Image Encryption Using Quantum 3D Mobius Scrambling and 3D Hyper-Chaotic Henon Map
Authors: Wang Ling , Ran Qiwen , Ding Junrong
Published: December 2023

In encryption technology, image scrambling is a common processing operation. This paper proposes a quantum version of the 3D Mobius scrambling transform based on the QRCI model, which changes not only the position of pixels but also the gray values. The corresponding quantum circuits are devised. Furthermore, an encryption scheme combining the quantum 3D Mobius transform with the 3D hyper-chaotic Henon map is suggested to protect the security of image information. To facilitate subsequent processing, the RGB color image is first represented with QRCI. Then, to achieve the pixel-level permutation effect, the quantum 3D Mobius transform is applied to scramble bit-planes and pixel positions. Ultimately, to increase the diffusion effect, the scrambled image is XORed with a key image created by the 3D hyper-chaotic Henon map to produce the encrypted image. Numerical simulations and result analyses indicate that our designed encryption scheme is secure and reliable. It offers better performance in the aspect of key space, histogram variance, and correlation coefficient than some of the latest algorithms.
Strain Energy and Entropy Based Scaling of Buckling Modes
Authors: Kala Zdeněk
Published: December 2023

A new utilization of entropy in the context of buckling is presented. The novel concept of connecting the strain energy and entropy for a pin-ended strut is derived. The entropy of the buckling mode is extracted through a surrogate model by decomposing the strain energy into entropy and virtual temperature. This concept rationalizes the ranking of buckling modes based on their strain energy under the assumption of given entropy. By assigning identical entropy to all buckling modes, they can be ranked according to their deformation energy. Conversely, with identical strain energy assigned to all the modes, ranking according to entropy is possible. Decreasing entropy was found to represent the scaling factors of the buckling modes that coincide with the measurement of the initial out-of-straightness imperfections in IPE160 beams. Applied to steel plane frames, scaled buckling modes can be used to model initial imperfections. It is demonstrated that the entropy (scale factor) for a given energy roughly decreases with the inverse square of the mode index. For practical engineering, this study presents the possibility of using scaled buckling modes of steel plane frames to model initial geometric imperfections. Entropy proves to be a valuable complement to strain energy in structural mechanics.
Accelerator for Agglomeration in Sequencing Economics: “Leased” Industrial Zones
Authors: Kuchiki Akifumi
Published: December 2023

This paper identifies the importance of reducing fixed costs for establishing industrial zones as part of an agglomeration policy. China’s economic growth has been driven by the agglomeration of manufacturing firms via industrial zones that attract foreign direct investment. This investment enables the export of products by importing intermediate capital goods. According to the new trade theory of spatial economics, the number of firms in an agglomeration is inversely proportional to the fixed costs. The main accelerator of agglomeration after the master switch is the formation of segments that reduce firms’ fixed costs. Via a factor analysis of manufacturing agglomeration segments in sequencing economics, this paper finds that “leased” industrial zones are accelerator segments in the formation process of manufacturing agglomerations.