bluuebunny/crossref_metadata_2025 huggingface dataset:
Clear Cell Renal Cell Carcinoma: From Biology to Treatment
Authors: Kase Adam M. , George Daniel J. , Ramalingam Sundhar
Published: January 2023

The majority of kidney cancers are detected incidentally and typically diagnosed at a localized stage, however, the development of regional or distant disease occurs in one-third of patients. Over 90% of kidney tumors are renal cell carcinomas, of which, clear cell is the most predominate histologic subtype. Von Hippel Lindau (VHL) gene alterations result in the overexpression of growth factors that are central to the pathogenesis of clear cell carcinoma. The therapeutic strategies have revolved around this tumor suppressor gene and have led to the approval of tyrosine kinase inhibitors (TKI) targeting the vascular endothelial growth factor (VEGF) axis. The treatment paradigm shifted with the introduction of immune checkpoint inhibitors (ICI) and programed death-1 (PD-1) inhibition, leading to durable response rates and improved survival. Combinations of TKI and/or ICIs have become the standard of care for advanced clear cell renal cell carcinoma (ccRCC), changing the outlook for patients, with several new and promising therapeutic targets under development.
Application Prospects of Triphenylphosphine-Based Mitochondria-Targeted Cancer Therapy
Authors: Cheng Xiaoxia , Feng Dong , Lv Junyu , Cui Xiaoman , Wang Yichen , Wang Qun , Zhang Lei
Published: January 2023

Cancer is one of the leading causes of death and the most important impediments to the efforts to increase life expectancy worldwide. Currently, chemotherapy is the main treatment for cancer, but it is often accompanied by side effects that affect normal tissues and organs. The search for new alternatives to chemotherapy has been a hot research topic in the field of antineoplastic medicine. Drugs targeting diseased tissues or cells can significantly improve the efficacy of drugs. Therefore, organelle-targeted antitumor drugs are being explored, such as mitochondria-targeted antitumor drugs. Mitochondria is the central site of cellular energy production and plays an important role in cell survival and death. Moreover, a large number of studies have shown a close association between mitochondrial metabolism and tumorigenesis and progression, making mitochondria a promising new target for cancer therapy. Combining mitochondrial targeting agents with drug molecules is an effective way of mitochondrial targeting. In addition, hyperpolarized tumor cell membranes and mitochondrial membrane potentially allow selective accumulation of mitochondria-targeted drugs. This enhances the direct killing of tumor cells by drug molecules while minimizing the potential toxicity to normal cells. In this review, we discuss the common pro-mitochondrial agents, the advantages of triphenylphosphine (TPP) in mitochondrial-targeted cancer therapy and systematically summarize various TPP-based mitochondria-targeting anticancer drugs.
Stochasticity and Drug Effects in Dynamical Model for Cancer Stem Cells
Authors: Mori Ludovico , Ben Amar Martine
Published: January 2023

The Cancer Stem Model allows for a dynamical description of cancer colonies which accounts for the existence of different families of cells, namely stem cells, highly proliferating and quasi-immortal, and differentiated cells, both undergoing cellular processes under numerous activated pathways. In the present work, we investigate a dynamical model numerically, as a system of coupled differential equations, and include a plasticity mechanism, of differentiated cells turning into a stem state if the stem concentration drops low. We are particularly interested in the stability of the model once we introduce stochastically evolving parameters, associated with environmental and cellular intrinsic variabilities, as well as the response of the model after introducing a drug therapy. As long as we stay within the characteristic time scale of the system, defined on the base of the needed time for the trajectories to converge on stable states, we observe that the system remains stable for the main parameters evolving stochastically according to white noise. As for the drug treatments, we discuss a model both for the kinetics and the dynamics of the substance in the organism, and then consider the impact of different types of therapies in a few particular examples, outlining some interesting mechanisms, such as the tumor growth paradox, that possibly impact the outcome of therapy significantly.
Breast Cancer Prediction Using Fine Needle Aspiration Features and Upsampling with Supervised Machine Learning
Authors: Shafique Rahman , Rustam Furqan , Choi Gyu Sang , Díez Isabel de la Torre , Mahmood Arif , Lipari Vivian , Velasco Carmen Lili Rodríguez , Ashraf Imran
Published: January 2023

Breast cancer is one of the most common invasive cancers in women and it continues to be a worldwide medical problem since the number of cases has significantly increased over the past decade. Breast cancer is the second leading cause of death from cancer in women. The early detection of breast cancer can save human life but the traditional approach for detecting breast cancer disease needs various laboratory tests involving medical experts. To reduce human error and speed up breast cancer detection, an automatic system is required that would perform the diagnosis accurately and timely. Despite the research efforts for automated systems for cancer detection, a wide gap exists between the desired and provided accuracy of current approaches. To overcome this issue, this research proposes an approach for breast cancer prediction by selecting the best fine needle aspiration features. To enhance the prediction accuracy, several feature selection techniques are applied to analyze their efficacy, such as principal component analysis, singular vector decomposition, and chi-square (Chi2). Extensive experiments are performed with different features and different set sizes of features to investigate the optimal feature set. Additionally, the influence of imbalanced and balanced data using the SMOTE approach is investigated. Six classifiers including random forest, support vector machine, gradient boosting machine, logistic regression, multilayer perceptron, and K-nearest neighbors (KNN) are tuned to achieve increased classification accuracy. Results indicate that KNN outperforms all other classifiers on the used dataset with 20 features using SVD and with the 15 most important features using a PCA with a 100% accuracy score.
Generation of Stable Epithelial–Mesenchymal Hybrid Cancer Cells with Tumorigenic Potential
Authors: Tedja Roslyn , Alvero Ayesha B. , Fox Alexandra , Cardenas Carlos , Pitruzzello Mary , Chehade Hussein , Bawa Tejeshwhar , Adzibolosu Nicholas , Gogoi Radhika , Mor Gil
Published: January 2023

Purpose: Cancer progression, invasiveness, and metastatic potential have been associated with the activation of the cellular development program known as epithelial-to-mesenchymal transition (EMT). This process is known to yield not only mesenchymal cells, but instead an array of cells with different degrees of epithelial and mesenchymal phenotypes with high plasticity, usually referred to as E/M hybrid cells. The characteristics of E/M hybrid cells, their importance in tumor progression, and the key regulators in the tumor microenvironment that support this phenotype are still poorly understood. Methods: In this study, we established an in vitro model of EMT and characterized the different stages of differentiation, allowing us to identify the main genomic signature associated with the E/M hybrid state. Results: We report that once the cells enter the E/M hybrid state, they acquire stable anoikis resistance, invasive capacity, and tumorigenic potential. We identified the hepatocyte growth factor (HGF)/c-MET pathway as a major driver that pushes cells in the E/M hybrid state. Conclusions: Herein, we provide a detailed characterization of the signaling pathway(s) promoting and the genes associated with the E/M hybrid state.
Duration of Immunotherapy in Non-Small Cell Lung Cancer Survivors: A Lifelong Commitment?
Authors: Putzu Carlo , Canova Stefania , Paliogiannis Panagiotis , Lobrano Renato , Sala Luca , Cortinovis Diego Luigi , Colonese Francesca
Published: January 2023

Lung cancer is one of the most common human malignancies and the leading cause of cancer-related death worldwide. Novel therapeutic approaches, like targeted therapies against specific molecular alterations and immunotherapy, have revolutionized in the last decade the oncological outcomes in patients affected by non-small cell lung cancer (NSCLC). The advent of immunotherapy for the treatment of NSCLC has significantly improved overall and progression-free survival, as well as the patient’s quality of life in comparison to traditional chemotherapy. Currently, it is estimated that long-term survival can be achieved in more than 15% of NSCLC patients treated with immunotherapy. Therefore, the optimal duration of immunotherapy in long survivors needs to be established to avoid overtreatment, side effects, and high costs and at the same time, protect them from potential disease relapse or progression. We performed a narrative review to discuss all the aspects related to the optimal duration of immunotherapy in long survivors with NSCLC. Data regarding the duration of immunotherapy in the most impacting clinical trials were collected, along with data regarding the impact of toxicities, side effects, and costs for healthcare providers. In addition, the two-year immunotherapy scheme in patients who benefit from first-line or subsequent treatment lines are examined, and the need for biomarkers that can predict outcomes during and after immunotherapy cessation in patients affected by NSCLC are discussed.
Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Breast Cancer: Evidence from a General Female Population and a Mammographic Screening Cohort in Sweden
Authors: Hu Kejia , Feychting Maria , Lu Donghao , Sjölander Arvid , Czene Kamila , Hall Per , Fang Fang
Published: January 2023

A link has been proposed between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of breast cancer. There is, however, insufficient data regarding the subtype and stage of breast cancer, and few studies have assessed the interaction between the use of NSAIDs and breast density or previous breast disorders. There is also a lack of data from population-based studies. We first conducted a nested case-control study within the general female population of Sweden, including 56,480 women with newly diagnosed breast cancer during 2006–2015 and five breast cancer-free women per case as controls, to assess the association of NSAID use with the risk of incident breast cancer, focusing on subtype and stage of breast cancer as well as the interaction between NSAID use and previous breast disorders. We then used the Karolinska Mammography Project for Risk Prediction of Breast Cancer (Karma) cohort to assess the interaction between NSAID use and breast density in relation to the risk of breast cancer. Conditional logistic regression was used to estimate the hazard ratio (HR) and a 95% confidence interval (CI) was used for breast cancer in relation to the use of aspirin and non-aspirin NSAIDs. In the nested case-control study of the general population, exclusive use of aspirin was not associated with the risk of breast cancer, whereas exclusive use of non-aspirin NSAIDs was associated with a modestly higher risk of stage 0–2 breast cancer (HR: 1.05; 95% CI: 1.02–1.08) but a lower risk of stage 3–4 breast cancer (HR 0.80; 95% CI: 0.73–0.88). There was also a statistically significant interaction between the exclusive use of NSAIDs and previous breast disorders (p for interaction: <0.001). In the analysis of Karma participants, the exclusive use of non-aspirin NSAIDs was associated with a lower risk of breast cancer among women with a breast dense area of >40 cm2 (HR: 0.72; 95% CI: 0.59–0.89). However, the possibility of finding this by chance cannot be ruled out. Overall, we did not find strong evidence to support an association between the use of NSAIDs and the risk of breast cancer.
S-Palmitoylation of Synaptic Proteins in Neuronal Plasticity in Normal and Pathological Brains
Authors: Buszka Anna , Pytyś Agata , Colvin Domnic , Włodarczyk Jakub , Wójtowicz Tomasz
Published: January 2023

Protein lipidation is a common post-translational modification of proteins that plays an important role in human physiology and pathology. One form of protein lipidation, S-palmitoylation, involves the addition of a 16-carbon fatty acid (palmitate) onto proteins. This reversible modification may affect the regulation of protein trafficking and stability in membranes. From multiple recent experimental studies, a picture emerges whereby protein S-palmitoylation is a ubiquitous yet discrete molecular switch enabling the expansion of protein functions and subcellular localization in minutes to hours. Neural tissue is particularly rich in proteins that are regulated by S-palmitoylation. A surge of novel methods of detection of protein lipidation at high resolution allowed us to get better insights into the roles of protein palmitoylation in brain physiology and pathophysiology. In this review, we specifically discuss experimental work devoted to understanding the impact of protein palmitoylation on functional changes in the excitatory and inhibitory synapses associated with neuronal activity and neuronal plasticity. The accumulated evidence also implies a crucial role of S-palmitoylation in learning and memory, and brain disorders associated with impaired cognitive functions.
Endocannabinoid 2-Arachidonoylglycerol Levels in the Anterior Cingulate Cortex, Caudate Putamen, Nucleus Accumbens, and Piriform Cortex Were Upregulated by Chronic Restraint Stress
Authors: Zhai Qing , Islam Ariful , Chen Bin , Zhang Hengsen , Chi Do Huu , Mamun Md. Al , Takahashi Yutaka , Sato Noriko , Yamasue Hidenori , Nakajima Yoshiki , Nagashima Yu , Sano Fumito , Sato Tomohito , Kahyo Tomoaki , Setou Mitsutoshi
Published: January 2023

Endocannabinoid 2-arachidonoylglycerol (2-AG) has been implicated in habituation to stress, and its augmentation reduces stress-induced anxiety-like behavior. Chronic restraint stress (CRS) changes the 2-AG levels in some gross brain areas, such as the forebrain. However, the detailed spatial distribution of 2-AG and its changes by CRS in stress processing-related anatomical structures such as the anterior cingulate cortex (ACC), caudate putamen (CP), nucleus accumbens (NAc), and piriform cortex (PIR) are still unclear. In this study, mice were restrained for 30 min in a 50 mL-centrifuge tube for eight consecutive days, followed by imaging of the coronal brain sections of control and stressed mice using desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The results showed that from the forebrain to the cerebellum, 2-AG levels were highest in the hypothalamus and lowest in the hippocampal region. 2-AG levels were significantly (p < 0.05) upregulated and 2-AG precursors levels were significantly (p < 0.05) downregulated in the ACC, CP, NAc, and PIR of stressed mice compared with control mice. This study provided direct evidence of 2-AG expression and changes, suggesting that 2-AG levels are increased in the ACC CP, NAc, and PIR when individuals are under chronic stress.
Effect of Thyroxine on the Structural and Dynamic Features of Cardiac Mitochondria and Mitophagy in Rats
Authors: Venediktova Natalya , Solomadin Ilya , Starinets Vlada
Published: January 2023

This work investigated the effect of thyroxine on the biogenesis and quality control system in rat heart mitochondria. In hyperthyroid rats, the concentrations of free triiodothyronine and thyroxine increased severalfold, indicating the development of hyperthyroidism in these animals. The electron microscopy showed 58% of cardiac mitochondria to be in a swollen state. Some organelles were damaged and had a reduced number of cristae. Multilamellar bodies formed from cristae/membranes were found in the vacuolated part of the mitochondria. The hyperthyroidism caused no changes to mitochondrial biogenesis in the investigated animals. At the same time, the levels of mitochondrial dynamics proteins OPA1 and Drp1 increased in the hyperthyroid rats. The administration of thyroxine to the animals led to a decrease in the amount of PINK1 and Parkin in heart tissue. The data suggest that excess thyroid hormones lead to changes in mitochondrial dynamics and impair Parkin-dependent mitophagy in hyperthyroid rat heart.
PAX6 Expression Patterns in the Adult Human Limbal Stem Cell Niche
Authors: Polisetti Naresh , Schlunck Günther , Reinhard Thomas
Published: January 2023

Paired box 6 (PAX6), a nuclear transcription factor, determines the fate of limbal epithelial progenitor cells (LEPC) and maintains epithelial cell identity. However, the expression of PAX6 in limbal niche cells, primarily mesenchymal stromal cells (LMSC), and melanocytes is scarce and not entirely clear. To distinctly assess the PAX6 expression in limbal niche cells, fresh and organ-cultured human corneoscleral tissues were stained immunohistochemically. Furthermore, the expression of PAX6 in cultured limbal cells was investigated. Immunostaining revealed the presence of PAX6-negative cells which were positive for vimentin and the melanocyte markers Melan-A and human melanoma black-45 in the basal layer of the limbal epithelium. PAX6 staining was not observed in the limbal stroma. Moreover, the expression of PAX6 was observed by Western blot in cultured LEPC but not in cultured LMSC or LM. These data indicate a restriction of PAX6 expression to limbal epithelial cells at the limbal stem cell niche. These observations warrant further studies for the presence of other PAX isoforms in the limbal stem cell niche.
Review of Accelerated Bridge Construction Systems for Bridge Superstructures and Their Adaptability for Cold Weather
Authors: Aurier Louis , Hassan Munzer , Jaworski Jan , Guizani Lotfi
Published: January 2023

The application of Accelerated Bridge Construction methods (ABC) to build, renovate and rehabilitate aging bridges is most likely to reduce the economic and social impacts of projects. This is especially relevant in countries with severe winter climates, where bridge construction is typically interrupted during the winter period. The objective of this study is to present the state of the art related to elements, systems, connections and materials used for bridge superstructures in ABC projects and to highlight their adaptability to cold or northern climate countries. The literature review and presentation of results are based on the gathering of Prefabricated/Precast Bridge Elements and Systems (PBES) used for ABC projects in North America and which are also used in many countries around the world. Following this inventory, and after grouping the PBES, connections and materials, the authors were able to identify the possibility of adapting the ABC method for countries with cold and northern climates. Products that can be used down to −6 °C for connections are presented, and future research orientations are proposed.
Active Ingredients and Carriers in Nutritional Eco-Cosmetics
Authors: Morganti Pierfrancesco , Lohani Alka , Gagliardini Alessandro , Morganti Gianluca , Coltelli Maria-Beatrice
Published: January 2023

Beauty and personal care became a significant part of the global economy for two reasons: (1) The elderly growing in the global population and (2) the desire of women and men to appear younger and more attractive. Thus, both young and old people are looking for revolutionary nutritional eco-cosmetics (combined use of cosmeceuticals and nutraceuticals) manufactured by natural active ingredients, using biopolymers as substrates, and made by innovative and sustainable technologies. Consequently, the market of both cosmetics and diet supplements is continually growing together with the request of natural active ingredients, including bio-peptides and biological macromolecules such as chitin and lignin. Therefore, both consumers and industry need to recover innovative active ingredients and carriers (vehicles), naturally derived and supported by advanced methods for controlling their effectiveness and safeness on skin and mucous membrane layers. The use of selected bio-ingredients, such as hyaluronic acid and bio-mimetic peptides, obtained by advanced, innovative and sustainable bio nanotechnologies, will be of interest to develop smart cosmeceutical and nutraceutical formulations. Innovation is considered the key business strategy to drive sustainable economic growth. For trying to reduce waste and produce sustainable, biodegradable and innovative products, the realization of new non-woven tissues, used as carriers for making innovative cosmeceuticals and nutraceuticals was considered. Both carriers and active ingredients have been obtained from food waste to reduce loss and pollution. This review will report a brief description of the skin functions, trying also to focus and discuss some of the active ingredients and carriers used in nutritional eco-cosmetics to clarify the supposed mechanism of action, effectiveness and safeness of both active ingredients and carriers, as well as the supposed activity of beauty and personal care products.
Matere Bonds in Technetium Compounds: CSD Survey and Theoretical Considerations
Authors: Burguera Sergi , Gomila Rosa M. , Bauzá Antonio , Frontera Antonio
Published: January 2023

Noncovalent interactions involving metals as electron acceptors are continuously under investigation. The term “matere bond” has been proposed to identify noncovalent donor–acceptor interactions where elements of group 7 of the periodic table play the role of the electrophilic site. Most of the works on matere bonds involve rhenium atoms usually in +7 oxidation state. This work emphasizes for the first time their importance in technetium derivatives in several oxidation states (+7, +6, +5, and +3). The Cambridge Structural Database (CSD) in combination with density functional theory (DFT) calculations are used to demonstrate the structure directing role of matere bonds in X-ray structures, even involving anion⋯anion interactions. Further characterization of the matere bonds is provided using Molecular Electrostatic Potential (MEP) surface calculations, the “Quantum Theory of Atoms in Molecules” (QTAIM), and Natural Bond Orbital (NBO) analyses. It should be emphasized that some types of matere bonds reported herein have not been previously described in literature.
Bending 90° Waveguides in Nd:YAG Crystal Fabricated by a Combination of Femtosecond Laser Inscription and Precise Diamond Blade Dicing
Authors: Zha Hao , Yao Yicun , Wang Minghong , Chen Nankuang , Zhang Liqiang , Bai Chenglin , Liu Tao , Ren Yingying , Jia Yuechen
Published: January 2023

In this paper, a low-loss 90°-bending design in femtosecond laser-induced double-line waveguides is theoretically proposed and experimentally demonstrated. The bending is realized based on the total internal reflection of a corner mirror (made by precise diamond blade dicing) located at the intersection of a pair of waveguides perpendicular to each other. The waveguide bending performance was birefringence free, with the insertion loss of each bending below 0.8 dB. This method provides great flexibility and has great potential for the design of integrated photonics based on femtosecond laser-inscribed crystalline materials.
Synthetic Conditions for Obtaining Different Types of Amine-Holding Silica Particles and Their Sorption Behavior
Authors: Melnyk Inna , Tomina Veronika , Stolyarchuk Nataliya
Published: January 2023

The Stöber version of a sol-gel method of co-condensation of two alkoxysilanes (structuring tetraethoxysilane (TEOS) and functionalising N-containing silane) in an ammonia medium was used for the one-pot synthesis of spherical silica particles with ≡Si(CH2)3NH2, ≡Si(CH2)3NH(CH2)2NH2, and ≡[Si(CH2)3NH]2 functional groups with available groups content of 1.3–2.3 mmol/g. The materials were researched by a range of methods, including SEM, TEM, IR spectroscopy, 13C, and 29Si solid-state NMR spectroscopy, acid-base titration, and thermal analysis to identify the peculiarities of the morphology, functional groups content, composition, and thermal resistance of the surface layers in the synthesised samples. The type of N-containing silane was shown to affect the structure and properties of the synthesised spherical particles. The silane with the simplest, 3-aminopropyl, functional group caused the formation of nonporous material composed of large 600–800 nm spherical microparticles. Meanwhile, the complication of functional groups enhanced the emergence of small 15 nm primary particles and the origination of porosity, generated by the slits between particles and particle agglomerates. Thereafter, the sorption properties of the synthesised hybrid materials for nickel(II) and copper(II)ions, and bovine serum albumin (BSA) were also found to be dependent on the structure of the materials and the type of incorporated functional group. The maximal static sorption capacity values towards the targeted adsorbates were shown by the samples with 3-aminopropyl groups (1.27 mmol Ni/g), diamine groups (1.09 mmol Cu/g), and secondary amine groups (204.6 mg BSA/g). The conducted research opens up the prospects of directed one-pot synthesis of amino-functionalised hybrid organosilica materials for different applications.
Photoresponsive Organic Molecular Crystals
Authors: Tong Fei , Al-Kaysi Rabih O. , Kitagawa Daichi
Published: January 2023

The Special Issue on “Photoresponsive Molecular Crystals” is a collection of four original research articles dedicated to theoretical and experimental research works providing new insights and experimental findings in the field of photoresponsive crystals [...]
Multiple Exceptional Points in APT–Symmetric Cantor Multilayers
Authors: Fang Ming , Wang Yang , Zhang Pu , Xu Haihong , Zhao Dong
Published: January 2023

In this study, we explore the anisotropic reflection of light waves around the exceptional points (EPs) in anti-parity-time−symmetric (APT−symmetric) Cantor dielectric multilayers. This one-dimensional fractal structure governed by the Cantor substitution law is modulated to satisfy APT symmetry. The Cantor multilayers are aperiodic and support optical fractal resonances. The optical fractal effect combined with APT symmetry can induce multiple exceptional points (EPs) in the parameter space by modulating the loss coefficient of materials and optical frequency. Reflection anisotropy for light waves incident from two opposite directions presents unidirectional suppression and enhancement around EPs. This study can be utilized for multiple wavelengths of photonic suppressors and reflectors.
Using First-Principles Calculations to Investigate the Interfacial Properties of Ni(100)/Ni3Al(100) Eutectic Structures
Authors: Ding Zongye , Long Weimin , Jiu Yongtao , Yang Tianxing , Zhong Sujuan , Yang Jingwei , Fu Weijie , Qiao Jian
Published: January 2023

In this paper, the interfacial stabilities of six different stacking interface configurations of Ni(100)/Ni3Al(100) eutectic structures with AlNi termination and Ni termination are calculated by using first-principles methods. The calculated adhesion work and interface energy indicate that the “Center” site stacking interface configurations are more stable than the “Top” and “Bridge” site stacking interface models. The partial density of states (PDOS) and the charge density difference confirm that the bonding characteristic of the Ni-terminated “Center” site stacking interface of the Ni(100)/Ni3Al(100) eutectic structure is metallic, while the bond at the AlNi-terminated “Center” site interface is a combination of covalent and metallic bonds. A comprehensive analysis of the interface energy, PDOS and charge density difference confirms that the AlNi-terminated “Center” site stacking interface configuration of the Ni(100)/Ni3Al(100) eutectic structure is the most stable eutectic interface model.
Lead-Free Piezoelectric Ceramic Micro-Pressure Thick Films
Authors: Chen Kai-Huang , Cheng Chien-Min , Chen Ying-Jie , Chen Mei-Li
Published: January 2023

In this study, non-stoichiometry lead-free piezoelectric ceramic Li0.058(K0.48Na0.535)0.966(Nb0.9Ta0.1)O3 (LKNNT) thick films were deposited on Pt/Ti/Si substrates using spin-coating method technology to form a LKNNT/Pt/Ti/Si structure of the micro-pressure thick films. Additionally, the influence on the crystalline properties, surface microstructure images, and mechanical properties, and the piezoelectric properties of the non-stoichiometry lead-free piezoelectric ceramic Li0.058(K0.48Na0.535)0.966(Nb0.9Ta0.1)O3 (LKNNT) thick films were observed, analyzed, and calculated using X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), focused ion beam (FIB) microscopy, nano-indention technology, and other instruments. This study was divided into two parts: The first part was the investigation into the fabrication parameters and properties of the bottom layer (Pt) and buffer layer (Ti). The Pt/Ti/Si structures were achieved by the DC sputtering method, and then the rapid thermal annealing (RTA) post-treatment process was used to re-arrange the grains and reduce defects in the lead-free Li0.058(K0.48Na0.535)0.966(Nb0.9Ta0.1)O3 (LKNNT) thick films. In the second part, lead-free Li0.058(K0.48Na0.535)0.966(Nb0.9Ta0.1)O3 (LKNNT) powder was prepared by the solid-state reaction method, and then acetic acid (C2H4O2) solvent was added to form a slurry for spin-coating technology processing. The fabrication parameters, thick film micro-structure, crystalline properties, nano-indention technology, and the piezoelectric coefficient characteristics of the developed lead-free Li0.058(K0.48Na0.535)0.966(Nb0.9Ta0.1)O3 (LKNNT)/Pt/Ti/Si structure of the micro-pressure thick film devices a were investigated. According to the experimental results, the optimal fabrication processing parameters of the lead-free Li0.058(K0.48Na0.535)0.966(Nb0.9Ta0.1)O3 (LKNNT) were an RTA temperature of 500 °C, a Ti buffer-layer thickness of 273.9 nm, a Pt bottom electrode-layer thickness of 376.6 nm, a theoretical density of LKNNT of 4.789 g/cm3, a lattice constant of 3.968 × 10−8 cm, and a d33 value of 150 pm/V. Finally, regarding the mechanical properties of the micro-pressure devices for when a microforce of 3 mN was applied, the thick film revealed a hardness of 60 MPa, a Young’s modulus of 13 GPa, and an elasticity interval of 1.25 μm, which are suitable for future applications of micro-pressure devices.
Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients
Authors: Rosso Roberta , D’Alonzo Marta , Bounous Valentina Elisabetta , Actis Silvia , Cipullo Isabella , Salerno Elena , Biglia Nicoletta
Published: January 2023

Background: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality of women with hormone-receptor-positive tumors, but poor adherence remains a significant problem. The aim of this study was to analyze AET side effects and their impact on adherence to treatment. Methods: A total of 373 breast cancer patients treated with AET filled out a specific questionnaire during their follow up visits at the Breast Unit of our Centre. Results: Side effects were reported by 81% of patients, 84% of those taking tamoxifen and 80% of those taking aromatase inhibitors (AIs). The most common side effect in the tamoxifen group was hot flashes (55.6%), while in the AI group it was arthralgia (60.6%). The addition of GnRH agonists to both tamoxifen and AI significantly worsened all menopausal symptoms. Overall, 12% of patients definitively discontinued AET due to side effects, 6.4% during the first 5 years and 24% during extended therapy. Patients who had previously received chemotherapy or radiotherapy reported a significantly lower discontinuation rate. Conclusions: AET side effects represent a significant problem in breast cancer survivors leading to irregular assumption and discontinuation of therapy. Adherence to AET may be improved by trustful patient–physician communication and a good-quality care network.
Shearwater Eggs in Lobos 3, a Holocene Site of Fuerteventura (Canary Islands)
Authors: Núñez-Lahuerta Carmen , Moreno-Azanza Miguel , Pérez-Pueyo Manuel , Del-Arco-Aguilar M. del Carmen , Del-Arco-Aguilar Mercedes , Siverio-Batista Celia , Castillo-Ruiz Carolina , Cruzado-Caballero Penélope
Published: January 2023

Two eggs (L29 and N28) were recovered in the Holocene site of Lobos 3, (Islote de Lobos, north Fuerteventura, Canary Islands), the site has been interpreted as a purple dye workshop from the Early Roman Empire Epoch. For the first time, eggs from a Holocene deposit of the Canary Islands have been analyzed in terms of size, shape, and biomineral structure, and studied on the basis of several thin sections and SEM analysis. The analysis of the remains allowed the assignation of both eggs to Procellariidae birds, thanks to the relative proportion of the eggshell layers and the vesiculation patterns. The size of the eggs allowed the assignation of L29 to cf. Calonectris/Puffinus, and to cf. Puffinus for N28. The absence of more structural analysis on Procellariiformes eggshells prevent a more specific assignation. The accumulation pattern of the eggs is compatible with a seasonal occupation pattern of the Roman site.
Rotifers of Inter-Forest Springs
Authors: Jekatierynczuk-Rudczyk Elżbieta , Ejsmont-Karabin Jolanta
Published: January 2023

Springs are often considered as “hotspots” of aquatic biodiversity. However, small organisms, such as rotifers, substantially contribute to secondary production, but they are rarely investigated in springs. We surveyed the rotifer fauna of 47 springs in the Knyszyn Forest (north-eastern Poland) in summer and autumn 2014–2015. We hypothesized that stream communities of Rotifera may be specific to this habitat. Rotifer samples were taken using a Plexiglas tube in the spring current. Concurrently, water temperature, pH, conductivity, water redox potential and phosphorus and nitrogen concentrations were determined. The springs did not differ statistically in water quality and were stable regarding their temperature and conductivity. Rotifer densities and mean number of monogonont species were very low both in summer and autumn. Nevertheless, the total number of species recorded in all springs was relatively high and accounted for 101 in total. Although strongly differentiated, the rotifer fauna contained a set of several species common to most of the springs. Most of the recorded species are eurytopic and widely spread in water ecosystems. Only the concentration of magnesium and chloride ions had an impact on Monogononta numbers.
Predicting the Habitat Suitability and Distribution of Two Species of Mound-Building Termites in Nigeria Using Bioclimatic and Vegetation Variables
Authors: Istifanus Aiki P. , Abdelmutalab Azrag. G. A. , Pirk Christian W. W. , Yusuf Abdullahi A.
Published: January 2023

Temperature is an important factor determining the abundance, distribution and diversity of termite species. Thus, termites are affected by changing climate and have to adopt different means of surviving in order to avoid extinction. Using termite occurrence data, bioclimatic variables and vegetation cover, we modelled and predicted the current and future habitat suitability for mound-building termites in Nigeria. Of the 19 bioclimatic variables and the vegetation index (NDVI) tested, only six were significant and eligible as predictors of habitat suitability for the mound-building termites Macrotermes subhyalinus and M. bellicosus. Under current climatic conditions (2022), the northwest, northeast and central regions are highly suitable for M. subhyalinus, while the distribution of M. bellicosus decreased in the North West, North East and in the Central region. However, regarding habitat suitability for the future (2050), there was a predicted range expansion into suitable areas for the two termite species. The increase in temperature due to global warming has an effect which can either result in migration or sometimes extinction of termite species within an ecosystem. Here, we have predicted habitat suitability for the two mound-building termite species under current and future climatic scenarios, and how the change in climatic variables would lead to an expansion in their range across Nigeria.
An Overview of Marine Non-Indigenous Species Found in Three Contrasting Biogeographic Metropolitan French Regions: Insights on Distribution, Origins and Pathways of Introduction
Authors: Massé Cécile , Viard Frédérique , Humbert Suzie , Antajan Elvire , Auby Isabelle , Bachelet Guy , Bernard Guillaume , Bouchet Vincent M. P. , Burel Thomas , Dauvin Jean-Claude , Delegrange Alice , Derrien-Courtel Sandrine , Droual Gabin , Gouillieux Benoit , Goulletquer Philippe , Guérin Laurent , Janson Anne-Laure , Jourde Jérôme , Labrune Céline , Lavesque Nicolas , Leclerc Jean-Charles , Le Duff Michel , Le Garrec Vincent , Noël Pierre , Nowaczyk Antoine , Pergent-Martini Christine , Pezy Jean-Philippe , Raoux Aurore , Raybaud Virginie , Ruitton Sandrine , Sauriau Pierre-Guy , Spilmont Nicolas , Thibault Delphine , Vincent Dorothée , Curd Amelia
Published: January 2023

Biological invasions are one of the main global threats to biodiversity in terrestrial, freshwater and marine ecosystems worldwide, requiring effective inventorying and monitoring programs. Here, we present an updated list of non-indigenous species in French marine and transitional waters. Focused on eukaryote pluricellular species found throughout the three metropolitan French marine regions (Western Mediterranean Sea, Bay of Biscay and the Northern Seas), a total of 342 non-indigenous, including 42 cryptogenic, species are listed as having been introduced since the 13th century. The majority of the species originated from the temperate Northern Pacific. They mainly arrived through both ballast and hull fouling and also are associated with shellfish farming activities. Most of them have been introduced since the 1970s, a time when maritime and aquaculture trade intensified. Despite important human-aided opportunities for species transfer between the three marine regions (for instance, via recreational boating or aquaculture transfers), only a third of these NIS are common to all regions, as expected due to their environmental specificities.
Indonesian Vegetables: Searching for Antioxidant and Antidiabetic Therapeutic Agents
Authors: Rani Dinar Mutia , Hanafi Nur , Sudarko  , Rachmawati Dessy , Siswoyo Tri Agus , Christianty Fransiska Maria , Dewi Ika Puspita , Nugraha Ari Satia
Published: January 2023

Diabetes mellitus prevalence in Indonesia reached 19.5 million cases, which has affected the productive age population. The indigenous people of Indonesia are blessed with the second largest biodiversity in the world, including vegetables, which are also prepared as medicaments. Vegetables are well-known as natural antioxidants which evolved in metabolic disease prevention, including diabetes mellitus. One of the Government of Indonesia’s strategic plans in health is to develop new antidiabetic from nature. In this study, nineteen vegetable species were collected and evaluated for their antioxidant activity followed by computational-based bioprospecting. The study indicated Ipomoea aquatica, Paederia foetida, Plumbago zeylanica, Nauclea pallida, Sauropus androgynus, Wrightia pubescens, and Psophocarpus tetragonolobus to contain high antioxidant components. Computational experiments on chemical constituents previously reported from the same species showed potent compounds with high affinity against α-glucosidase (3a4a). 7-O-β-D-glucopyranosyl-dihydroquercetin-3-O-α-D-glucopyranoside 1, stigmasterol 7, and chitanone 12 are the most potent compounds from Ipomoea aquatica, Paederia foetida, and Plumbago zeylanica, respectively, which are superior to a standard drug, acarbose. The four vegetable species are feasible for conventional drug sources or developed as botanical dosage according to the Indonesian government’s strategic plan. Further studies are necessary to ensure adequate preclinical and clinical data to meet the requirement of safe and potent medicine. Nevertheless, Nauclea pallida and Psophocarpus tetragonolobus are valuable species with potent yet understudied antioxidant sources.
Predictive Value of Annenxin A1 for Disease Severity and Prognosis in Patients with Community-Acquired Pneumonia
Authors: Gu Minghao , Han Xiudi , Liu Xuedong , Sui Fengxiang , Zhang Quansan , Pan Shengqi
Published: January 2023

This prospective, single-center study evaluated the clinical utility of annenxin (Anx)A1 level as a biomarker for determining the severity of illness and predicting the risk of death in hospitalized patients with community-acquired pneumonia (CAP). A total of 105 patients (53 with severe [S]CAP, 52 with non-SCAP) were enrolled from December 2020 to June 2021. Demographic and clinical data were recorded. Serum AnxA1 concentration on days one and six after admission was measured by enzyme-linked immunosorbent assay. AnxA1 level at admission was significantly higher in SCAP patients than in non-SCAP patients (p < 0.001) irrespective of CAP etiology and was positively correlated with Pneumonia Severity Index and Confusion, Uremia, Respiratory Rate, Blood Pressure, and Age ≥ 65 Years score. AnxA1 level was significantly lower on day six after treatment than on day one (p = 0.01). Disease severity was significantly higher in patents with AnxA1 level ≥254.13 ng/mL than in those with a level <254.13 ng/mL (p < 0.001). Kaplan–Meier analysis of 30-day mortality showed that AnxA1 level ≤670.84 ng/mL was associated with a significantly higher survival rate than a level >670.84 ng/mL. These results indicate that AnxA1 is a useful biomarker for early diagnosis and prognostic assessment of CAP.
Maternal Methyl-Enriched Diet Increases DNMT1, HCN1, and TH Gene Expression and Suppresses Absence Seizures and Comorbid Depression in Offspring of WAG/Rij Rats
Authors: Sarkisova Karine Yu. , Fedosova Ekaterina A. , Shatskova Alla B. , Rudenok Margarita M. , Stanishevskaya Vera A. , Slominsky Petr A.
Published: January 2023

The reduced expression of the HCN1 ion channel in the somatosensory cortex (SSC) and mesolimbic dopamine deficiency are thought to be associated with the genesis of spike-wave discharges (SWDs) and comorbid depression in the WAG/Rij rat model of absence epilepsy. This study aimed to investigate whether the maternal methyl-enriched diet (MED), which affects DNA methylation, can alter DNMT1, HCN1, and TH gene expression and modify absence seizures and comorbid depression in WAG/Rij offspring. WAG/Rij mothers were fed MED (choline, betaine, folic acid, vitamin B12, L-methionine, zinc) or a control diet for a week before mating, during pregnancy, and for a week after parturition. MED caused sustained suppression of SWDs and symptoms of comorbid depression in the offspring. Disease-modifying effects of MED were associated with increased expression of the DNMT1 and HCN1 genes in the SSC and hippocampus, as well as DNMT1, HCN1, and TH genes in the nucleus accumbens. No changes in gene expression were detected in the hypothalamus. The results indicate that maternal MED can suppress the genetic absence epilepsy and comorbid depression in offspring. Increased expression of the DNMT1, HCN1, and TH genes is suggested to be a molecular mechanism of this beneficial phenotypic effect.
Preoperative Hilar and Mediastinal Lymph Node Staging in Patients with Suspected or Diagnosed Lung Cancer: Accuracy of 18F-FDG-PET/CT:A Retrospective Cohort Study of 138 Patients
Authors: Damirov Fuad , Büsing Karen , Yavuz Gökce , Hatz Rudolf , Manapov Farkhad , Michels Julia , Hohenberger Peter , Roessner Eric
Published: January 2023

The aim of this study was to evaluate the diagnostic accuracy of integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of suspected or proven lung cancer, and to investigate potential risk factors for false negative and false positive HMLN metastases. We retrospectively analyzed 162 consecutive patients with suspected or pathologically proven non-small cell lung cancer (NSCLC). The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficacy of 18F-FDG-PET/CT. Univariate and multivariate analyses were conducted to detect risk factors of false positives and false negatives. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of integrated 18F-FDG-PET/CT in detecting HMLN metastases were 59.1% (26/44), 69.1% (65/94), 47.3% (26/55), 78.3% (65/83), and 65.9% (91/138), respectively. The ROC curve showed an area under the curve (AUC) of 0.625 (95%-CI 0.468–0.782). The incidence of false negative and false positive HMLN metastases was 21.7% (18/83) and 52.7% (29/55), respectively. Our data shows that integrated 18F-FDG-PET/CT staging provides lower specificity and sensitivity. This confirms the ESTS guideline on lymph node staging for PET-positive HMLN. Yet it advocates more invasive staging even for PET-negative HMLN.
Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma
Authors: Vishweswaraiah Sangeetha , Ramachandra Nallur , Joshi Neha , Parthasarathi Ashwaghosha , Kaleem Ullah Mohammed , Siddaiah Jayaraj , Holla Amrutha , Chakraborty Samarpana , Agrawal Anurag , Mahesh Padukudru
Published: January 2023

ADAM33 has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of ADAM33 SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case–control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of ADAM33, namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied ADAM33 SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele “T” for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. ADAM33 gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population.