bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Genetic Characterization of Blastocystis in Sheep and Pigs in Shanxi Province, North China: From a Public Health Perspective
Authors: Wei Chang-Ning , Qin Rui-Lin , Zhang Zhen-Huan , Zheng Wen-Bin , Liu Qing , Gao Wen-Wei , Zhu Xing-Quan , Xie Shi-Chen
Published: September 2023

Blastocystis is a common zoonotic intestinal protozoan and causes a series of gastrointestinal symptoms in humans and animals via the fecal–oral route, causing economic losses and posing public health problems. At present, the prevalence and genetic structure of Blastocystis in sheep and pigs in Shanxi province remains unknown. Thus, the present study collected 492 sheep fecal samples and 362 pig fecal samples from three representative counties in northern, central and southern Shanxi province for the detection of Blastocystis based on its SSU rRNA gene. The results showed that the overall prevalence of Blastocystis in the examined sheep and pigs were 16.26% and 14.09%, respectively. Sequences analyses showed that four known subtypes (ST5, ST10, ST14 and ST30) in sheep and two subtypes (ST1 and ST5) in pigs were detected in this study, with ST5 being the predominate subtype among the study areas. Phylogenetic analysis showed that the same subtypes were clustered into the same branch. This study reveals that sheep and pigs in Shanxi province are hosts for multiple Blastocystis subtypes, including the zoonotic subtypes (ST1 and ST5), posing a risk to public health. Baseline epidemiological data are provided that help in improving our understanding of the role of zoonotic subtypes in Blastocystis transmission.
Tick-borne Pathogen Detection and Its Association with Alterations in Packed Cell Volume of Dairy Cattle in Thailand
Authors: Adjou Moumouni Paul Franck , Galon Eloiza May , Tumwebaze Maria Agnes , Byamukama Benedicto , Ngasaman Ruttayaporn , Tiwananthagorn Saruda , Kamyingkird Ketsarin , Inpankaew Tawin , Xuan Xuenan
Published: September 2023

Tick-borne diseases (TBDs) massively impact bovine production. In endemic countries, animals are often subclinically infected, showing no signs of the illness. Anemia is a hallmark of TBDs, but there is inadequate information on its presence in infected Thai cattle. In the present study, 265 cattle from four provinces in Thailand were surveyed to identify tick-borne pathogens (TBPs) and to evaluate the changes in the packed cell volume (PCV) values associated with detection. Microscopy and polymerase chain reaction (PCR) were also compared for TBP detection. Babesia/Theileria/Hepatozoon was detected in 33.58% (89/265) of the cattle samples. Specifically, Babesia bovis (9/265), B. bigemina (12/265), Theileria orientalis (62/265), and Anaplasma marginale (50/265) were identified using species-specific assays. Significant decreases in the mean PCV levels were observed in cattle that were positive for at least one TBP (p < 0.001), Babesia/Theileria/Hepatozoon (p < 0.001), T. orientalis (p < 0.001), and A. marginale (p = 0.049). The results of PCR and microscopy for the detection of TBPs suggested slight and fair agreement between the two detection tools. The present findings contribute to a better understanding of TBDs in the field and shall facilitate the formulation of effective control for TBDs in Thailand.
Canine Somatic Mutations from Whole-Exome Sequencing of B-Cell Lymphomas in Six Canine Breeds—A Preliminary Study
Authors: Kim Sungryong , Kim Namphil , Kang Hyo-Min , Jang Hye-Jin , Lee Amos Chungwon , Na Ki-Jeong
Published: September 2023

Canine lymphoma (CL) is one of the most common malignant tumors in dogs. The cause of CL remains unclear. Genetic mutations that have been suggested as possible causes of CL are not fully understood. Whole-exome sequencing (WES) is a time- and cost-effective method for detecting genetic variants targeting only the protein-coding regions (exons) that are part of the entire genome region. A total of eight patients with B-cell lymphomas were recruited, and WES analysis was performed on whole blood and lymph node aspirate samples from each patient. A total of 17 somatic variants (GOLIM4, ITM2B, STN1, UNC79, PLEKHG4, BRF1, ENSCAFG00845007156, SEMA6B, DSC1, TNFAIP1, MYLK3, WAPL, ADORA2B, LOXHD1, GP6, AZIN1, and NCSTN) with moderate to high impact were identified by WES analysis. Through a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 17 genes with somatic mutations, a total of 16 pathways were identified. Overall, the somatic mutations identified in this study suggest novel candidate mutations for CL, and further studies are needed to confirm the role of these mutations.
Examining the Effects of Hyperbaric Oxygen Therapy on the Cardiovascular System and Oxidative Stress in Insulin-Treated and Non-Treated Diabetic Rats
Authors: Ristic Petar , Savic Maja , Bolevich Sergey , Bolevich Stefani , Orlova Alexandra , Mikhaleva Anastasiya , Kartashova Anna , Yavlieva Koka , Nikolic Turnic Tamara , Pindovic Bozidar , Djordjevic Katarina , Srejovic Ivan , Zivkovic Vladimir , Jakovljevic Vladimir
Published: September 2023

Background: This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3–5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks). Methods: Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. Results: NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals. Conclusions: NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.
Behavioural Correlates of Lemur Scent-Marking in Wild Diademed Sifakas (Propithecus diadema) in the Maromizaha Forest (Madagascar)
Authors: Miaretsoa Longondraza , Torti Valeria , Petroni Flavia , Valente Daria , De Gregorio Chiara , Ratsimbazafy Jonah , Carosi Monica , Giacoma Cristina , Gamba Marco
Published: September 2023

Scent-marking through odours from excreta and glandular secretions is widespread in mammals. Among primates, diurnal group-living lemurs show different deployment modalities as part of their strategy to increase signal detection. We studied the diademed sifaka (Propithecus diadema) in the Maromizaha New Protected Area, Eastern Madagascar. We tested whether the scent-marking deposition occurred using a sequential rubbing of different body parts. We also tested if glands (i.e., deposition of glandular secretions) were more frequently rubbed than genital orifices (i.e., deposition of excreta) by comparing different kinds of rubbing behaviour. We then investigated if the depositor’s rank and sex affected the sequence of rubbing behaviour, the height at which the scent-marking happened, and the tree part targeted. We found that glandular secretions were often deposited with urine, especially in dominant individuals. The probability of anogenital and chest marking was highest, but chest rubbing most frequently occurred in dominant males. Markings were deposited at similar heights across age and sex, and tree trunks were the most used substrate. Males exhibited long and more complex scent-marking sequences than females. Our results indirectly support the idea that diademed sifakas deploy a sex-dimorphic mixture of glandular secretions and excreta to increase the probability of signal detection by conspecifics.
Generation of a Virtual Cohort of Patients for in Silico Trials of Acute Ischemic Stroke Treatments
Authors: Bridio Sara , Luraghi Giulia , Ramella Anna , Rodriguez Matas Jose Felix , Dubini Gabriele , Luisi Claudio A. , Neidlin Michael , Konduri Praneeta , Arrarte Terreros Nerea , Marquering Henk A. , Majoie Charles B. L. M. , Migliavacca Francesco
Published: September 2023

The development of in silico trials based on high-fidelity simulations of clinical procedures requires the availability of large cohorts of three-dimensional (3D) patient-specific anatomy models, which are often hard to collect due to limited availability and/or accessibility and imaging quality. Statistical shape modeling (SSM) allows one to identify the main modes of shape variation and to generate new samples based on the variability observed in a training dataset. In this work, a method for the automatic 3D reconstruction of vascular anatomies based on SSM is used for the generation of a virtual cohort of cerebrovascular models suitable for computational simulations, useful for in silico stroke trials. Starting from 88 cerebrovascular anatomies segmented from stroke patients’ images, an SSM algorithm was developed to generate a virtual population of 100 vascular anatomies, defined by centerlines and diameters. An acceptance criterion was defined based on geometric parameters, resulting in the acceptance of 83 generated anatomies. The 3D reconstruction method was validated by reconstructing a cerebrovascular phantom lumen and comparing the result with an STL geometry obtained from a computed tomography scan. In conclusion, the final 3D models of the generated anatomies show that the proposed methodology can produce a reliable cohort of cerebral arteries.
An Identification Method of Feature Interpretation for Melanoma Using Machine Learning
Authors: Li Zhenwei , Ji Qing , Yang Xiaoli , Zhou Yu , Zhi Shulong
Published: September 2023

Melanoma is a fatal skin cancer that can be treated efficiently with early detection. There is a pressing need for dependable computer-aided diagnosis (CAD) systems to address this concern effectively. In this work, a melanoma identification method with feature interpretation was designed. The method included preprocessing, feature extraction, feature ranking, and classification. Initially, image quality was improved through preprocessing and k-means segmentation was used to identify the lesion area. The texture, color, and shape features of this region were then extracted. These features were further refined through feature recursive elimination (RFE) to optimize them for the classifiers. The classifiers, including support vector machine (SVM) with four kernels, logistic regression (LR), and Gaussian naive Bayes (GaussianNB) were applied. Additionally, cross-validation and 100 randomized experiments were designed to guarantee the generalization of the model. The experiments generated explainable feature importance rankings, and importantly, the model demonstrated robust performance across diverse datasets.
Research on Conditions and Influence Factors of an Acoustic Wave Acting as a Plane Wave in Tire Acoustic Cavity
Authors: Hu Xiaojun , Liu Xiandong , Shan Yingchun , He Tian
Published: September 2023

Tire acoustic cavity resonance noise (TACRN) contributes significantly to the interior noise of electric cars and passenger cars with lower powertrain noise, which affects the comfort of the ride. To suppress TACRN effectively, it is crucial to clarify the characteristics of TACRN. In previous studies, the acoustic wave in the tire acoustic cavity is straightforwardly assumed to be the plane wave for convenience. In fact, there exist strict conditions for the acoustic wave propagating in the pipeline to act as a plane wave. The aim of this paper is to make the characteristics and evolution of acoustic waves in tire acoustic cavities clear. To do so, a simplified model of the tire cavity is established, and the sound field distribution and the acoustic wave propagation characteristics in the tire cavity are analyzed based on the theory of acoustic waveguide. Then, the existence ranges of higher-order waves (non-plane waves), the conditions of an acoustic wave evolving into a plane wave, and the frequency range of a plane wave are investigated. Finally, the characteristics and evolution law of an acoustic wave in a tire acoustic cavity are obtained. The work in this paper may deepen the understanding of the characteristics and mechanism of acoustic waves in the tire cavity and be helpful and meaningful for analyzing and suppressing TACRN. Therefore, it is of practical significance to reduce TACRN transmitted to the vehicle and improve the sound quality inside the vehicle.
Special Issue on Optical Camera Communications and Applications
Authors: Singh Pankaj , Jung Sung-Yoon
Published: September 2023

Optical Camera Communication (OCC) is a groundbreaking technology that combines optical signals and image sensors for data transmission [...]
Adsorption of Mixed Dispersions of Silica Nanoparticles and an Amphiphilic Triblock Copolymer at the Water–Vapor Interface
Authors: Carbone Carlo , Rubio-Bueno Alejandra , Ortega Francisco , Rubio Ramón G. , Guzmán Eduardo
Published: September 2023

This study investigates the surface modification of hydrophilic silica nanoparticles by non-chemical adsorption of an amphiphilic triblock copolymer, Pluronic F-127, and elucidates its influence on the interfacial dispersion properties. The interaction between Pluronic F-127 and silica nanoparticles drives the formation of copolymer-decorated particles with increased hydrodynamic diameter and reduced effective charge as the copolymer concentration increases, while the opposite effect occurs as the particle concentration increases at a fixed polymer concentration. This indicates that increasing the copolymer concentration leads to an increase in the coating density, whereas increasing the particle concentration leads to a decrease. This is of paramount importance for modulating the reorganization of the Pluronic F-127 shell upon adsorption at fluid–fluid interfaces and, thus, the adsorption of the decorated nanoparticles at the interface and the rheological properties of the obtained layers. In fact, the relationship between copolymer concentration and interfacial tension, as well as the mechanical response of the interface, mirrors the patterns observed in Pluronic F-127 solutions, and only a shift mediated by the Pluronic F-127 concentration is found. This suggests that the presence of particles limits the space available for Pluronic F-127 molecules to reorganize at the interface but does not significantly affect the interfacial behavior of the particle-laden interface.
Volumetric Modulated Arc Therapy for Radiosurgery of Brain Metastases: A Single-Center Study
Authors: Sánchez-Villalobos José Manuel , Serna-Berna Alfredo , Salinas-Ramos Juan , Escolar-Pérez Pedro Pablo , Andreu-Gálvez Marina , Martínez-Alonso Emma , Pérez-Vicente José Antonio , Alcaraz Miguel
Published: September 2023

Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with a retrospective review of the medical records of patients with brain metastases treated with VMAT-RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index, and the survival estimated according to the Kaplan–Meier model from the date of radiosurgery, were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1–4 BMs, which were treated with five non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer, and 35% of the BMs were in the frontal lobe. The proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox regression model, KPS ≥ 70 (HRKPS < 70 = 2.59; p = 0.001) and higher DS-GPA (HRDS-GPAII = 0.55, p = 0.022; HRDS-GPAIII-IV = 0.38, p = 0.006) were associated with improved survival. In the univariate analysis, primary tumor, age, and the presence of metastases in the posterior fossa (PFBMs) were also significant. In conclusion, the VMAT-RS is a technique with an overall survival rate comparable to other radiosurgery techniques. The median survival is significantly longer for those with higher KPS and DS-GPA. Other variables, such as the type of primary tumor, age, and PFBMs, could also influence survival, although further studies are needed.
Recent Trends and Progress in Corrosion Inhibitors and Electrochemical Evaluation
Authors: Bijapur Kiran , Molahalli Vandana , Shetty Apoorva , Toghan Arafat , De Padova Paola , Hegde Gurumurthy
Published: September 2023

Science and engineering research studies are currently concentrating on synthesizing, designing, producing, and consuming ecologically benign chemical species to replace harmful chemicals. This is due to the increasing demands of conservation knowledge and strict ecological regulations. Numerous environmentally friendly substitutes produced from natural resources, including biopolymers, plant extracts, chemical pharmaceuticals (drugs), and so on, are now frequently used as inhibitors to replace dangerous corrosion inhibitors. Many compounds have been extensively used. A range of methods, including physisorption, chemisorption, barrier protection, thin-film growth, and electrochemical procedures, will be used to provide corrosion resistance. The various kinds of corrosion inhibitors (CIs), the mechanisms underlying inhibition, and the evaluation procedures have all been covered in-depth. This review provides an overview of the relevant literature in which researchers and scientists used different types of CIs, the effect of CIs on metals, and information about designs and mechanisms used to minimize corrosion in a variety of equipment composed of alloys or metals, along with electrochemical evaluation studies. This review will provide scholars with fresh insights to advance the discipline.
Particle Counter Design Upgrade for Euro 7
Authors: Biró Norbert , Szőllősi Dániel , Kiss Péter
Published: September 2023

This research article presents an optimized approach to enhance the performance of the APC exhaust gas particle analyzer, a significant instrument used for exhaust emission evaluation in diesel-powered vehicles considering EU regulations on pollutant emissions. The study aimed to address the challenge of particle counter contamination that often occurs during frequent exhaust gas measurements and leads to measurement interruptions until maintenance is conducted. To achieve this, a preparatory unit that extends the operational duration of the measurement system between maintenance intervals while preserving measurement accuracy was developed based on actual exhaust gas experiments. The preparatory unit comprises a condensate drainage system, cooling fan, HEPA filter, membrane pump, and interconnecting pipelines to prevent moisture and larger particle deposition, ensuring uninterrupted and accurate exhaust gas measurements. The research findings underscore the significance of reliable and precise exhaust gas emission measurements, contributing to advancements in particle counting technology and facilitating compliance with emissions regulations in various scientific and industrial applications. This study provides an objective representation of the proposed preparatory unit’s effectiveness in mitigating particle contamination with only 1.9% measurement variance, offering promising implications for the improvement of exhaust gas analysis methods.
On the Structure of Quantum Markov Chains on Cayley Trees Associated with Open Quantum Random Walks
Authors: Souissi Abdessatar , Hamdi Tarek , Mukhamedov Farrukh , Andolsi Amenallah
Published: September 2023

Quantum Markov chains (QMCs) and open quantum random walks (OQRWs) represent different quantum extensions of the classical Markov chain framework. QMCs stand as a more profound layer within the realm of Markovian dynamics. The exploration of both QMCs and OQRWs has been a predominant focus over the past decade. Recently, a significant connection between QMCs and OQRWs has been forged, yielding valuable applications. This bridge is particularly impactful when studying QMCs on tree structures, where it intersects with the realm of phase transitions in models naturally arising from quantum statistical mechanics. Furthermore, it aids in elucidating statistical properties, such as recurrence and clustering. The objective of this paper centers around delving into the intricate structure of QMCs on Cayley trees in relation to OQRWs. The foundational elements of this class of QMCs are built upon using classical probability measures that encompass the hierarchical nature of Cayley trees. This exploration unveils the pivotal role that the dynamics of OQRWs play in shaping the behavior of the Markov chains under consideration. Moreover, the analysis extends to their classical counterparts. The findings are further underscored by the examination of notable examples, contributing to a comprehensive understanding of the outcomes.
Effects of Serial Polydrug Use on the Rewarding and Aversive Effects of the Novel Synthetic Cathinone Eutylone
Authors: Manke Hayley N. , Nunn Samuel S. , Sulima Agnieszka , Rice Kenner C. , Riley Anthony L.
Published: September 2023

Background: As individual synthetic cathinones become scheduled and regulated by the Drug Enforcement Administration (DEA), new ones regularly are produced and distributed. One such compound is eutylone, a novel third-generation synthetic cathinone whose affective properties (and abuse potential) are largely unknown. The following experiments begin to characterize these effects and how they may be impacted by drug history (a factor affecting reward/aversion for other drugs of abuse). Methods: Eutylone was assessed for its ability to induce conditioned taste avoidance (CTA; aversive effect) and conditioned place preference (CPP; rewarding effect) and their relationship (Experiment 1). Following this, the effects of exposure to cocaine or 3,4-methylenedioxymethamphetamine [MDMA] on eutylone’s affective properties were investigated (Experiment 2). Results: Eutylone produced dose-dependent CTA and CPP (Experiment 1), and these endpoints were unrelated. Pre-exposure to cocaine and MDMA differentially impacted taste avoidance induced by eutylone (MDMA > cocaine) and did not impact eutylone-induced place preference. Conclusions: These data indicate that eutylone, like other synthetic cathinones, has co-occurring, independent rewarding and aversive effects that may contribute to its abuse potential and that these effects are differentially impacted by drug history. Although these studies begin the characterization of eutylone, future studies should examine the impact of other factors on eutylone’s affective properties and its eventual reinforcing effects (i.e., intravenous self-administration [IVSA]) to predict its use and abuse liability.
Minimum Cost Design for Rectangular Isolated Footings Taking into Account That the Column Is Located in Any Part of the Footing
Authors: Luévanos-Rojas Arnulfo
Published: September 2023

This work presents a new model for obtaining the cheapest design for a rectangular isolated footing, taking into account that the column is located in any part of the footing. The methodology is developed by integration to obtain the moments, bending shear and punching shear according to the American Concrete Institute ACI 318-14. This document presents the simplified and precise equations of the four moments, four bending shears and one punching shear acting on the footing. Some designs have been developed by the trial and error method to determine the footing dimensions, and later the thickness and steel area of the footing are obtained. Some authors present the minimum cost design for a rectangular isolated footing taking into account that the column is located in the center of gravity of the footing, and other authors present very complex algorithms. Numerical examples are presented to obtain the minimum cost design of rectangular isolated footings under biaxial bending, and some results are compared with those of other authors considering the same conditions. The new model presents a smaller contact area with the soil and a lower design cost than those presented by other authors.
An Experimental and Mechanical Study of a Two-Layer, Bioinspired Seismic Isolator for Multistory Buildings
Authors: Qaderi Saeedeh , Adinolfi Valentina , Germano Giovanni , Benzoni Gianmario , Luciano Raimondo , Fraternali Fernando
Published: September 2023

This work illustrates a novel two-layer version of the sliding–stretching isolator recently proposed in the literature to protect buildings and infrastructure from seismic waves. Such a device has a biomimetic character and is formed by rigid members mimicking the role played by human arms and legs when walking or running, and deformable membranes referred to as tendons. It tunes the elongation and contraction of the tendons to recenter the system and to safely avoid resonance of the system with earthquake frequencies. The paper illustrates how is possible to generalize the mechanical model of the one-layer isolator (SSI1) formulated in previous studies to account for the presence of the second layer (SSI2 system). The two-layer device doubles the lateral displacement capacity of the system, while keeping the footprint of the device fixed. Shake-table tests on reduced-scaled SSI2 prototypes are employed to derive the constitutive parameters of the proposed mechanical model and to experimentally validate it. The given results demonstrate that SSI2 systems pave the way to real-life applications of sliding–stretching isolators in multistory buildings.
Indoor Microclimate and Microbiological Risks in Heritage Buildings: A Case Study of the Neologic Sinagogue, Oradea, Romania
Authors: Ilieș Dorina Camelia , Blaga Lucian , Hassan Thowayeb H. , Ilieș Alexandru , Caciora Tudor , Grama Vasile , Herman Grigore Vasile , Dejeu Paula , Zdringa Mihaela , Marshall Tracy , Pereș Ana Cornelia , Bekzot Janzakov
Published: September 2023

Heritage buildings face risks related to the degradation of exhibited or stored artefacts, up to their destruction over time, as well as the health of workers and visitors. The main causes are microclimatic parameters (temperature, humidity, brightness, particles suspension, pollutants, degree of ventilation or air circulation), biological (bacteria, fungi, molds and insects) and anthropogenic ones (improper maintenance of the building and overcrowding of rooms). In accordance with these, the present study considers a quantitative and qualitative analysis of the air quality and the degree of microbiological contamination of the surfaces and the air inside a synagogue in the municipality of Oradea, Romania. The microbiological study highlighted the presence of some potentially harmful genera of fungi (Alternaria sp., Penicillium sp., Aspergillus sp., Botrytis sp. and Cladosporium sp.) in the indoor air and on the surfaces inside the synagogue; suggesting an average degree of fungal contamination, with possible risk to individual health, especially in children and people with allergic status or allergic respiratory diseases. Statistical analysis concerning the occupational exposure to airborne microbes poses health risks to employees and visitors. Multivariate regression analysis results emphasize that higher symptoms scores were independently associated with experiencing a too low indoor air temperature; these symptoms would disappear within one to two hours after leaving the space. Air pollutants have become part of everyday life; therefore, consistent monitoring of indoor environments offers an effective approach to prevent or minimize the adverse health risk to building occupants in spaces such as heritage buildings.
Clinical Experience with Abemaciclib in Patients Previously Treated with Another CDK 4/6 Inhibitor in a Tertiary Hospital: A Case Series Study
Authors: de Luna Aguilar Alicia Milagros , Fuentes Javier David Benitez , Ortega Anselmi Justo , Olalla Inoa Jennifer , Flores Navarro Paloma , Lopez de Sá Alfonso , Fuentes Antras Jesus , Rodríguez Rey Cristina , Ortega Candil Aída , Moreno Antón Fernando , García Sáenz Jose Ángel
Published: September 2023

The three approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including abemaciclib, have shown differences in their preclinical, pharmacological, and clinical data. Abemaciclib stands out for its broader target range and more rapid and intense activity. It has demonstrated efficacy as a monotherapy or in combination with tamoxifen in endocrine-refractory metastatic breast cancer (MBC) patients with prior chemotherapy. However, the clinical data on abemaciclib after exposure to previous CDK4/6 inhibitors are limited. In this single-center retrospective case series, we identified all patients who received abemaciclib until February 2022 after experiencing documented progression on palbociclib or ribociclib. The safety profile and clinical outcomes of abemaciclib treatment in this specific patient cohort were evaluated. Eleven patients were included in this retrospective case series, nine receiving abemaciclib with tamoxifen. Eight patients had visceral involvement, and the median age was 69 (ranging from 42 to 84). The median time from the end of prior CDK4/6 inhibitor treatment to abemaciclib initiation was 17.5 months (ranging from 3 to 41 months). Patients had undergone a median of three prior therapies (ranging from 1 to 7), including chemotherapy in 54.5% of cases. The median follow-up time was six months (ranging from 1 to 22 months). The median progression-free survival (PFS) was 8 months (95% CI 3.9–12). Five patients continued abemaciclib treatment, and one patient with liver metastases achieved a complete hepatic response. The most common adverse events were diarrhea (72.7%, no grade ≥ 3) and asthenia (27.3%, no grade ≥ 3). Our preliminary findings suggest that abemaciclib could be an effective and safe treatment option for MBC patients who have previously received palbociclib or ribociclib.
Association between Metabolic Syndrome and Risk of Hypopharyngeal Cancer: A Nationwide Cohort Study from Korea
Authors: Kang Jeong Wook , Cheong Hyeon-Kyoung , Kim Su Il , Lee Min Kyeong , Lee Young Chan , Oh In-Hwan , Eun Young-Gyu
Published: September 2023

This study evaluated the relationship between metabolic syndrome (MS) and the risk of hypopharyngeal cancer. This retrospective cohort study used data from the Korean National Health Insurance Research Database. A total of 4,567,890 participants who underwent a health checkup in 2008 were enrolled. The participants were followed until 2019, and the incidence of hypopharyngeal cancer was analyzed. We evaluated the risk of hypopharyngeal cancer according to the presence of MS, including obesity, dyslipidemia, hypertension, and diabetes, using a multivariate Cox proportional hazards model adjusted for age, sex, alcohol consumption, and smoking. During the follow-up period, 821 were newly diagnosed with hypopharyngeal cancer. MS was inversely associated with the risk of hypopharyngeal cancer (hazard ratio (HR), 0.83 [95% confidence interval (CI), 0.708–0.971]). Large waist circumference and high triglyceride levels among MS elements were both inversely related to the risk of hypopharyngeal cancer (HR: 0.82 [95% CI, 0.711–0.945] and 0.83 [95% CI, 0.703–0.978], respectively). The risk of hypopharyngeal cancer decreased with increasing comorbidity of MS in women (N = 0 vs. N = 1–2 vs. N ≥ 3; HR = 1 vs. HR = 0.511 [95% CI, 0.274–0.952] vs. HR = 0.295 [95% CI, 0.132–0.66]), but not in men. This study may improve our etiological understanding of hypopharyngeal cancer.
Granzyme B Expression in the Tumor Microenvironment as a Prognostic Biomarker for Patients with Triple-Negative Breast Cancer
Authors: Mizoguchi Kimihisa , Kawaji Hitomi , Kai Masaya , Morisaki Takafumi , Hayashi Saori , Takao Yuka , Yamada Mai , Shimazaki Akiko , Osako Tomofumi , Arima Nobuyuki , Okido Masayuki , Oda Yoshinao , Nakamura Masafumi , Kubo Makoto
Published: September 2023

Tumor-infiltrating lymphocytes in the tumor microenvironment are important in the treatment of triple-negative breast cancer (TNBC). Cytotoxic T cells produce cytokines and cytotoxic factors, such as perforin and granzyme, which induce apoptosis by damaging target cells. To identify biomarkers of these cells, we investigated granzyme B (GZMB) in the tumor microenvironment as a biomarker of treatment response and prognosis in 230 patients with primary TNBC who underwent surgery without preoperative chemotherapy between January 2004 and December 2014. Programmed cell death ligand 1 (PD-L1) positivity was defined as a composite positive score ≥10 based on the PD-L1 immunostaining of tumor cells and immune cells. GZMB-high was defined as positivity in ≥1% of tumor-infiltrating lymphocytes (TILs). Among the 230 TNBC patients, 117 (50.9%) had CD8-positive infiltrating tumors. In the PD-L1-positive group, a Kaplan–Meier analysis showed that GZMB-high TNBC patients had better recurrence-free survival (RFS) and overall survival (OS) than GZMB-low patients and that OS was significantly longer (RFS: p = 0.0220, OS: p = 0.0254). A multivariate analysis also showed significantly better OS in PD-L1- and GZMB-high patients (hazard ratio: 0.25 (95% IC: 0.07–0.88), p = 0.03). Our findings indicate that GZMB is a useful prognostic biomarker in PD-L1-positive TNBC patients.
Radiolabeled NGR-Based Heterodimers for Angiogenesis Imaging: A Review of Preclinical Studies
Authors: Trencsényi György , Halmos Gábor , Képes Zita
Published: September 2023

Since angiogenesis/neoangiogenesis has a major role in tumor development, progression and metastatic spread, the establishment of angiogenesis-targeting imaging and therapeutic vectors is of utmost significance. Aminopeptidase N (APN/CD13) is a pivotal biomarker of angiogenic processes abundantly expressed on the cell surface of active vascular endothelial and various neoplastic cells, constituting a valuable target for cancer diagnostics and therapy. Since the asparagine–glycine–arginine (NGR) sequence has been shown to colocalize with APN/CD13, the research interest in NGR-peptide-mediated vascular targeting is steadily growing. Earlier preclinical experiments have already demonstrated the imaging and therapeutic feasibility of NGR-based probes labeled with different positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radionuclides, including Gallium-68 (68Ga), Copper-64 (64Cu), Technetium-99m (99mTc), Lutetium-177 (177Lu), Rhenium-188 (188Re) or Bismuth-213 (213Bi). To improve the tumor binding affinity and the retention time of single-receptor targeting peptides, NGR motifs containing heterodimers have been introduced to identify multi-receptor overexpressing malignancies. Preclinical studies with various tumor-bearing experimental animals provide useful tools for the investigation of the in vivo imaging behavior of NGR-based heterobivalent ligands. Herein, we review the reported preclinical achievements on NGR heterodimers that could be highly relevant for the development of further target-specific multivalent compounds in diagnostic and therapeutic settings.
Understanding and Therapeutic Targeting of the p53 Network
Authors: Bacher Susanne , Schmitz M. Lienhard
Published: September 2023

Signaling networks function as highly intertwined regulatory hubs rather than linear cascades with a single endpoint [...]
Organocatalysis in the Chemical Transformations
Authors: da Silva Adriana Maria
Published: September 2023

Organocatalysis has been a breakthrough in chemical transformations becoming viable the conversion of challenging reactions through the sustainable use of small organic molecules as catalysts [...]
Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene
Authors: Dixit Garima , Pappas Benjamin A. , Bhardwaj Gourav , Schanz Willow , Maretzky Thorsten
Published: September 2023

Functional analysis of somatic mutations in tumorigenesis facilitates the development and optimization of personalized therapy for cancer patients. The fibroblast growth factor receptor 2 (FGFR2) gene is frequently mutated in endometrial cancer (EC), but the functional implications of FGFR2 mutations in cancer development remain largely unexplored. In this study, we introduced a reliable and readily deployable screening method to investigate the effects of FGFR2 mutations. We demonstrated that distinct mutations in FGFR2 can lead to differential downstream consequences, specifically affecting a disintegrin- and metalloprotease 17 (ADAM17)-dependent shedding of the epidermal growth factor receptor (EGFR) ligand heparin-binding EGF-like growth factor (HB-EGF) and phosphorylation of mitogen-activated protein kinases (MAPKs). Furthermore, we showed that the distribution of mutations within the FGFR2 gene can influence their oncogenic effects. Together, these findings provide important insights into the complex nature of FGFR2 mutations and their potential implications for EC. By unraveling the distinct effects of different mutations, our study contributes to the identification of personalized treatment strategies for patients with FGFR2-mutated cancers. This knowledge has the potential to guide the development of targeted therapies that specifically address the underlying molecular alterations associated with FGFR2 mutations, ultimately improving patient outcomes in EC and potentially other cancer types characterized by FGFR2 mutations.
New High-Affinity Thrombin Aptamers for Advancing Coagulation Therapy: Balancing Thrombin Inhibition for Clot Prevention and Effective Bleeding Management with Antidote
Authors: Ayass Mohamad Ammar , Griko Natalya , Pashkov Victor , Tripathi Trivendra , Zhang Jin , Ramankutty Nair Ramya , Okyay Tutku , Zhu Kevin , Abi-Mosleh Lina
Published: September 2023

Thrombin is a key enzyme involved in blood clotting, and its dysregulation can lead to thrombotic diseases such as stroke, myocardial infarction, and deep vein thrombosis. Thrombin aptamers have the potential to be used as therapeutic agents to prevent or treat thrombotic diseases. Thrombin DNA aptamers developed in our laboratory exhibit high affinity and specificity to thrombin. In vitro assays have demonstrated their efficacy by significantly decreasing Factor II activity and increasing PT and APTT times in both plasma and whole blood. Aptamers AYA1809002 and AYA1809004, the two most potent aptamers, exhibit high affinity for their target, with affinity constants (Kd) of 10 nM and 13 nM, respectively. Furthermore, the in vitro activity of these aptamers displays dose-dependent behavior, highlighting their efficacy in a concentration-dependent manner. In vitro stability assessments reveal that the aptamers remain stable in plasma and whole blood for up to 24 h. This finding is crucial for their potential application in clinical settings. Importantly, the thrombin inhibitory activity of the aptamers can be reversed by employing reverse complement sequences, providing a mechanism to counteract their anticoagulant effects when necessary to avoid excessive bleeding. These thrombin aptamers have been determined to be safe, with no observed mutagenic or immunogenic effects. Overall, these findings highlight the promising characteristics of these newly developed thrombin DNA aptamers, emphasizing their potential for therapeutic applications in the field of anticoagulation therapy. Moreover, the inclusion of an antidote in the coagulation therapy regimen can improve patient safety, ensure greater therapeutic efficacy, and minimize risk during emergency situations.
NMOSD IgG Impact Retinal Cells in Murine Retinal Explants
Authors: Wolf Hannah Nora , Ehinger Veronika , Guempelein Larissa , Banerjee Pratiti , Kuempfel Tania , Havla Joachim , Pauly Diana
Published: September 2023

Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system, characterized by autoantibodies against aquaporin-4. The symptoms primarily involve severe optic neuritis and longitudinally extensive transverse myelitis. Although the disease progression is typically relapse-dependent, recent studies revealed retinal neuroaxonal degeneration unrelated to relapse activity, potentially due to anti-aquaporin-4-positive antibodies interacting with retinal glial cells such as Müller cells. In this exploratory study, we analysed the response of mouse retinal explants to NMOSD immunoglobulins (IgG). Mouse retinal explants were treated with purified IgG from patient or control sera for one and three days. We characterized tissue response patterns through morphological changes, chemokine secretion, and complement expression. Mouse retinal explants exhibited a basic proinflammatory response ex vivo, modified by IgG addition. NMOSD IgG, unlike control IgG, increased gliosis and decreased chemokine release (CCL2, CCL3, CCL4, and CXCL-10). Complement component expression by retinal cells remained unaltered by either IgG fraction. We conclude that human NMOSD IgG can possibly bind in the mouse retina, altering the local cellular environment. This intraretinal stress may contribute to retinal degeneration independent of relapse activity in NMOSD, suggesting a primary retinopathy.
Analysis of the Relationship between APS Thermal Spray Parameters of Ni5Al Particles and Coating Characteristics
Authors: Fernández Roiz Adrián , Moreno José Andrés , Jorde Cerezo Guillermo , Solano Joaquín
Published: September 2023

The strength and characteristics of a coating are defined by the impact and temperature of the individual molten particles, as well as by the state of the surface to be coated. The parameters selected for thermal spraying determine the parameters of the particles in flight: temperature and velocity. These parameters can be determined by measuring the thermal radiation intensity of the particles in flight. The parameters that define the thermal spray are the mass flow rate, the intensity, and the H2 flow rate in the gas mixture to be propelled into the spray gun. On the other hand, the strength of the coating obtained can be estimated using its hardness and adhesion. In this study, a design of the experiments is developed to determine the relationships between the operating parameters and the parameters characterising the particles. From this design, the results obtained are analysed. The experimental results confirmed the direct relationship between intensity and particle temperature, consistent with the relationship between intensity and energy generated in the arc in the spray device. The velocities followed a similar relationship. Increasing the proportion of H2 in the feed gas led to a higher heat transfer to the particles, consistent with the information found in the literature. A similar effect was detected for the velocity. The adhesion and hardness increase with the speed and temperature of the particle in flight, which is related to a more efficient spatter-flattening process. The applied procedure provides an efficient methodology for the development of useful surfaces for the optimisation of thermal spraying processes.
Developing a Novel Hierarchical VPLS Architecture Using Q-in-Q Tunneling in Router and Switch Design
Authors: Biabani Morteza , Yazdani Nasser , Fotouhi Hossein
Published: September 2023

Virtual Private LAN Services (VPLS) is an ethernet-based Virtual Private Network (VPN) service that provides multipoint-to-multipoint Layer 2 VPN service, where each site is geographically dispersed across a Wide Area Network (WAN). The adaptability and scalability of VPLS are limited despite the fact that they provide a flexible solution for connecting geographically dispersed sites. Furthermore, the construction of tunnels connecting customer locations that are separated by great distances adds a substantial amount of latency to the user traffic transportation. To address these issues, a novel Hierarchical VPLS (H-VPLS) architecture has been developed using 802.1Q tunneling (also known as Q-in-Q) on high-speed and commodity routers to satisfy the additional requirements of new VPLS applications. The Vector Packet Processing (VPP) performs as the router’s data plane, and FRRouting (FRR), an open-source network routing software suite, acts as the router’s control plane. The router is designed to seamlessly forward VPLS packets using the Request For Comments (RFCs) 4762, 4446, 4447, 4448, and 4385 from The Internet Engineering Task Force (IETF) integrated with VPP. In addition, the Label Distribution Protocol (LDP) is used for Multi-Protocol Label Switching (MPLS) Pseudo-Wire (PW) signaling in FRR. The proposed mechanism has been implemented on a software-based router in the Linux environment and tested for its functionality, signaling, and control plane processes. The router is also implemented on commodity hardware for testing the functionality of VPLS in the real world. Finally, the analysis of the results verifies the efficiency of the proposed mechanism in terms of throughput, latency, and packet loss ratio.
Physical and Mathematical Models of Quantum Dielectric Relaxation in Electrical and Optoelectric Elements Based on Hydrogen-Bonded Crystals
Authors: Kalytka Valeriy , Mekhtiyev Ali , Neshina Yelena , Alkina Aliya , Aimagambetova Raushan , Mukhambetov Gabit , Bashirov Aleksandr , Afanasyev Dmitriy , Bilichenko Arkadiy , Zhumagulova Dinara , Ismailova Zukhra , Senina Yelena
Published: September 2023

The quantum statistical properties of the proton subsystem in hydrogen-bonded crystals (HBC) are investigated. Based on the non-stationary Liouville operator equation (taking into account a number of assumptions established in the experiment), a quantum kinetic equation is constructed for the ensemble of non-interacting protons (an ideal proton gas) moving in the crystal potential image perturbed by the external electric field. The balanced density matrix for the unperturbed proton subsystem is constructed using the quantum canonical Gibbs distribution, and the non-balanced density matrix is calculated from the solutions of the nonlinear quantum kinetic equation by methods in linear approximation of perturbation theory for the blocking electrode model. Full quantum mechanical averaging of the polarization operator makes it possible to study the theoretical frequency-temperature spectra of the complex dielectric permittivity (CDP) calculated using quantum relaxation parameters that differ significantly from their semiclassical counterparts. A scheme is presented for an analytical study of the dielectric loss tangent in the region of quantum nonlinear relaxation in HBC. The results obtained in the given paper are of scientific interest in developing the theoretical foundations of proton conduction processes in energy-independent memory elements (with anomalously high residual polarization) based on thin films of ferroelectric materials in the ultralow temperature range (1–10 K). The theoretical results obtained have a direct application to the study of the tunneling mechanisms of spontaneous polarization in ferroelectric HBC with a rectangular hysteresis loop, in particular in crystals of potassium dideutrophosphate (KDP), widely used in nonlinear optics and laser technology. The quantum properties of proton relaxation in HBC can be applied in the future to the study of solid-state electrolytes with high proton conductivity for hydrogen energy, capacitor technology (superionics, varicodes), and elements of MIS and MSM structures in the development of resonant tunnel diodes for microelectronics and computer technology.