bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Gene Expression, Splicing, and Allele-Specific Expression Vary among Macular Tissues and Clinical Stages of Age-Related Macular Degeneration
Authors: Shwani Treefa , Zhang Charles , Owen Leah A. , Shakoor Akbar , Vitale Albert T. , Lillvis John H. , Barr Julie L. , Cromwell Parker , Finley Robert , Husami Nadine , Au Elizabeth , Zavala Rylee A. , Graves Elijah C. , Zhang Sarah X. , Farkas Michael H. , Ammar David A. , Allison Karen M. , Tawfik Amany , Sherva Richard M. , Li Mingyao , Stambolian Dwight , Kim Ivana K. , Farrer Lindsay A. , DeAngelis Margaret M.
Published: November 2023

Age-related macular degeneration (AMD) is a leading cause of blindness, and elucidating its underlying disease mechanisms is vital to the development of appropriate therapeutics. We identified differentially expressed genes (DEGs) and differentially spliced genes (DSGs) across the clinical stages of AMD in disease-affected tissue, the macular retina pigment epithelium (RPE)/choroid and the macular neural retina within the same eye. We utilized 27 deeply phenotyped donor eyes (recovered within a 6 h postmortem interval time) from Caucasian donors (60–94 years) using a standardized published protocol. Significant findings were then validated in an independent set of well-characterized donor eyes (n = 85). There was limited overlap between DEGs and DSGs, suggesting distinct mechanisms at play in AMD pathophysiology. A greater number of previously reported AMD loci overlapped with DSGs compared to DEGs between disease states, and no DEG overlap with previously reported loci was found in the macular retina between disease states. Additionally, we explored allele-specific expression (ASE) in coding regions of previously reported AMD risk loci, uncovering a significant imbalance in C3 rs2230199 and CFH rs1061170 in the macular RPE/choroid for normal eyes and intermediate AMD (iAMD), and for CFH rs1061147 in the macular RPE/choroid for normal eyes and iAMD, and separately neovascular AMD (NEO). Only significant DEGs/DSGs from the macular RPE/choroid were found to overlap between disease states. STAT1, validated between the iAMD vs. normal comparison, and AGTPBP1, BBS5, CERKL, FGFBP2, KIFC3, RORα, and ZNF292, validated between the NEO vs. normal comparison, revealed an intricate regulatory network with transcription factors and miRNAs identifying potential upstream and downstream regulators. Findings regarding the complement genes C3 and CFH suggest that coding variants at these loci may influence AMD development via an imbalance of gene expression in a tissue-specific manner. Our study provides crucial insights into the multifaceted genomic underpinnings of AMD (i.e., tissue-specific gene expression changes, potential splice variation, and allelic imbalance), which may open new avenues for AMD diagnostics and therapies specific to iAMD and NEO.
The Role of Bcl-2 and Beclin-1 Complex in “Switching” between Apoptosis and Autophagy in Human Glioma Cells upon LY294002 and Sorafenib Treatment
Authors: Zając Adrian , Maciejczyk Aleksandra , Sumorek-Wiadro Joanna , Filipek Kamil , Deryło Kamil , Langner Ewa , Pawelec Jarosław , Wasiak Magdalena , Ścibiorski Mateusz , Rzeski Wojciech , Tchórzewski Marek , Reichert Michał , Jakubowicz-Gil Joanna
Published: November 2023

Background: Gliomas are the most malignant tumors of the central nervous system. One of the factors in their high drug resistance is avoiding programmed death (PCD) induction. This is related to the overexpression of intracellular survival pathways: PI3K-Akt/PKB-mTOR and Ras-Raf-MEK-ERK. Apoptosis and autophagy are co-existing processes due to the interactions between Bcl-2 and beclin-1 proteins. Their complex may be a molecular “toggle-switch” between PCD types. The aim of this research was to investigate the role of Bcl-2:beclin-1 complex in glioma cell elimination through the combined action of LY294002 and sorafenib. Methods: Drug cytotoxicity was estimated with an MTT test. The type of cell death was evaluated using variant microscopy techniques (fluorochrome staining, immunocytochemistry, and transmission electron microscopy), as well as the Bcl-2:beclin-1 complex formation and protein localization. Molecular analysis of PCD indicators was conducted through immunoblotting, immunoprecipitation, and ELISA testing. SiRNA was used to block Bcl-2 and beclin-1 expression. Results: The results showed the inhibitors used in simultaneous application resulted in Bcl-2:beclin-1 complex formation and apoptosis becoming dominant. This was accompanied by changes in the location of the tested proteins. Conclusions: “Switching” between apoptosis and autophagy using PI3K and Raf inhibitors with Bcl-2:beclin-1 complex formation opens new therapeutic perspectives against gliomas.
Oxygen Plasma-Induced Conversion of Silver Complex Ink into Conductive Coatings
Authors: Li Shasha , Cao Meijuan , Yang Ji , Guo Xiangjun , Sun Xinfeng , Wang Tao , Qi Yuansheng , Li Luhai , Zeng Huabin , Sun Meng
Published: November 2023

The use of AgNO3-polyvinyl alcohol (PVA) ink and oxygen plasma to form conductive coatings on plastic substrates was studied. It was found that oxygen plasma can decompose silver complexes to form metallic silver without high-temperature heating. The AgNO3-PVA ratio and plasma parameters (time, power) were optimized to obtain uniform conductive coatings. The morphology and electrical characteristics of the coatings were evaluated. Composite coatings with high reflectivity and good adhesion were prepared with a resistivity of 1.66 × 10−6 Ω·m using MOD inks with a silver ion mass fraction of 5%, after 300 W plasma treatment of the PET substrate for 2 min (the chamber temperature was 37.3 °C). These results demonstrate the potential feasibility of silver MOD inks and oxygen plasma treatment for the production of silver connectors, electromagnetic shielding films, and antimicrobial coatings on low-cost plastic substrates.
Meshfree Interpolation of Multidimensional Time-Varying Scattered Data
Authors: Skala Vaclav , Mourycova Eliska
Published: November 2023

Interpolating and approximating scattered scalar and vector data is fundamental in resolving numerous engineering challenges. These methodologies predominantly rely on establishing a triangulated structure within the data domain, typically constrained to the dimensions of 2D or 3D. Subsequently, an interpolation or approximation technique is employed to yield a smooth and coherent outcome. This contribution introduces a meshless methodology founded upon radial basis functions (RBFs). This approach exhibits a nearly dimensionless character, facilitating the interpolation of data evolving over time. Specifically, it enables the interpolation of dispersed spatio-temporally varying data, allowing for interpolation within the space-time domain devoid of the conventional “time-frames”. Meshless methodologies tailored for scattered spatio-temporal data hold applicability across a spectrum of domains, encompassing the interpolation, approximation, and assessment of data originating from various sources, such as buoys, sensor networks, tsunami monitoring instruments, chemical and radiation detectors, vessel and submarine detection systems, weather forecasting models, as well as the compression and visualization of 3D vector fields, among others.
Coming Back to the Basics. Comment on Cangir et al. A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors. Diagnostics 2022, 12, 416
Authors: Perrella Armando , Bagnacci Giulio , Di Meglio Nunzia , Di Martino Vito , Bellan Cristiana , Luzzi Luca , Mazzei Maria Antonietta , Volterrani Luca
Published: November 2023

We read with great interest the article by Cangir et al., “A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors”, published on 5 February 2022 [...]
AI-Driven Colon Cleansing Evaluation in Capsule Endoscopy: A Deep Learning Approach
Authors: Mascarenhas Saraiva Miguel José , Afonso João , Ribeiro Tiago , Cardoso Pedro , Mendes Francisco , Martins Miguel , Andrade Ana Patrícia , Cardoso Hélder , Mascarenhas Saraiva Miguel , Ferreira João , Macedo Guilherme
Published: November 2023

Gastroenterology is increasingly moving towards minimally invasive diagnostic modalities. The diagnostic exploration of the colon via capsule endoscopy, both in specific protocols for colon capsule endoscopy and during panendoscopic evaluations, is increasingly regarded as an appropriate first-line diagnostic approach. Adequate colonic preparation is essential for conclusive examinations as, contrary to a conventional colonoscopy, the capsule moves passively in the colon and does not have the capacity to clean debris. Several scales have been developed for the classification of bowel preparation for colon capsule endoscopy. Nevertheless, their applications are limited by suboptimal interobserver agreement. Our group developed a deep learning algorithm for the automatic classification of colonic bowel preparation, according to an easily applicable classification. Our neural network achieved high performance levels, with a sensitivity of 91%, a specificity of 97% and an overall accuracy of 95%. The algorithm achieved a good discriminating capacity, with areas under the curve ranging between 0.92 and 0.97. The development of these algorithms is essential for the widespread adoption of capsule endoscopy for the exploration of the colon, as well as for the adoption of minimally invasive panendoscopy.
Extracorporeal Membrane Oxygenation (ECMO)-Associated Coagulopathy in Adults
Authors: Frantzeskaki Frantzeska , Konstantonis Dimitrios , Rizos Michail , Kitsinelis Vasileios , Skyllas Georgios , Renieris Ioannis , Doumani Maria , Kolias Vasileios , Kefalidi Eirini , Angouras Dimitrios , Tsantes Argyrios , Tsangaris Iraklis
Published: November 2023

Extracorporeal membrane oxygenation (ECMO) is used for the management of severe respiratory and cardiac failure and as a bridge to achieve definite treatment or transplantation. ECMO-associated coagulopathy (EAC) is a frequent complication leading to high rates of thrombosis or severe haemorrhage, contributing to morbidity and mortality among patients. Understanding the pathophysiology of EAC is substantial for effectively managing patients on ECMO. We analyse the underlying mechanism of EAC and discuss the monitoring of the coagulation profile, combining the viscoelastic point-of-care assays with the conventional coagulation laboratory tests.
Is There an Adequate Therapeutic Approach to Thyroid Pathology in Patients with Down Syndrome?
Authors: Murillo-Llorente Maria Teresa , Pérez-Bermejo Marcelino , Llacer-Heredia Verónica , Tomás-Aguirre Beatriz , Valls-Arévalo Angel , Tomás-Aguirre Francisco
Published: November 2023

Thyroid dysfunction stands as the most prevalent endocrine disorder in individuals with Down syndrome, particularly showcasing both clinical and subclinical hypothyroidism. TSH and FT4 blood values serve as common diagnostic and treatment adjustment markers. In Down syndrome (DS), hormone values may deviate from those observed in the general population, which may lead to overdiagnosis and consequent iatrogenesis of subclinical hypothyroidism. The objective of this study was to analyze the appropriateness of the replacement therapeutic approach by identifying the TSH and FT4 values that can be considered normal in these patients. Methods: A cross-sectional study was conducted in 503 subjects with DS of both sexes and without age limit drawn from the Health Program for individuals with DS in Valencia (Spain) from February 1993 to November 2021. The exclusion criteria included hyperthyroidism, nodules, tumors, or individuals under treatment with drugs influencing iodine metabolism. The normality of data distribution was assessed using the Shapiro–Wilk test. Outliers were detected using the Reed’s criterion. Hormone values were estimated using quantile regression models for the 2.5th and 97.5th percentiles. Results: The normal values identified were 0.88–11.25 mIU/L for TSH and 0.71–1.63 ng/dL for FT4. The Wald test indicated no significant differences in the reference intervals based on age or sex. Conclusion: The establishment of these values, which, in people with DS, can be considered unique, is of great importance, allowing a watchful waiting attitude to be maintained before starting replacement therapy that is unnecessarily or adjusting medication in diagnosed cases.
High Proportion of Distributed PV Reliability Planning Method Based on Big Data
Authors: Fang Hualiang , Shang Lei , Dong Xuzhu , Tian Ye
Published: November 2023

The higher proportion of distributed photovoltaic and lower fossil energy integrated into the power network brings huge challenges in power supply reliability and planning. The distributed photovoltaic planning method based on big data is proposed. According to the impact of stochastic photovoltaics and loads on reliability planning, the probability model of distributed photovoltaic and load is analyzed, and the dynamic capacity–load ratios are presented based on big data. The multi-scenario generation and reduction algorithm of stochastic distributed photovoltaic and load planning is studied, and a source–load scenario matching model is proposed based on big data. According to the big data scenario of source–load, the reliability indexes and dynamic capacity–load ratio may be obtained. Finally, the IEEE 33-bus system is used as an example, and the results show that distributed photovoltaic planning methods based on big data can improve photovoltaic utilization and power supply reliability.
How to Repair the Next Generation of Wind Turbine Blades
Authors: Mishnaevsky Jr. Leon
Published: November 2023

Ensuring the sustainability of wind turbine blades will be an important requirement for new wind turbines to be installed in the coming years and decades. Several new wind turbines with blades from recyclable materials have already been installed, among which are blades based on recyclamine® and EzCiclo. The wind turbines of the new generation are subject to extreme mechanical and physical loading, can be damaged during service time, and will require maintenance and repair. In this paper, technologies for the repair and recycling of the new generation of materials for wind turbine blades are reviewed. Repair technologies for thermoplastic blades, recyclamine®- and vitrimer-based composites, and other new blade composites are discussed.
Valorization of Macauba (Acromia aculeata) for Integrated Production of Lipase by Yarrowia lipolytica and Biodiesel Esters
Authors: Buarque Filipe Smith , Farias Marcelle A. , Sales Júlio Cesar Soares , Carniel Adriano , Ribeiro Bernardo Dias , Lopes Verônica Regina de Oliveira , Castro Aline Machado , Coelho Maria Alice Zarur
Published: November 2023

Enzymatic biodiesel production is a potential eco-friendly alternative to the conventional chemical route which requires extensive study to reduce the costs associated with the application of commercial enzymes. Thus, this study aimed to develop a bioprocess using residues from macauba (Acrocomia aculeata) as raw material for lipase production in solid-state fermentation (SSF) by Yarrowia lipolytica. Then, the product obtained was used as a biocatalyst for the conversion (hydrolysis/esterification) of macauba acidic oil to biodiesel esters. Firstly, different SSF parameters (inoculum concentration, initial moisture content, and carbon and nitrogen levels) were investigated in a factorial design approach, using the cake from macauba fruit. Afterwards, moisture and urea concentration were shown to be statistically significant variables for lipase production. Lipase productnivities were 12.6 ± 0.6 U g−1 h−1 (at 24 h) for macauba fruit cake and 11.6 ± 1 U g−1 h−1 (at 20 h) for macauba pulp and peel cake. The solid enzymatic preparation (biocatalyst) showed optimized values at pH 6–7 at 37 °C, remaining stable (>70% retention) for 90 days at room temperature. Finally, enzymatic hydrolysis of the acidic oil from macauba reached 96% conversion (72 h) to fatty acids, and esterification of fatty acids reached 72% (biodiesel yield of 67%). The bioprocess described is a promising alternative for an integral and self-sufficient valorization of the macauba products.
The Genesis of Jewish Genealogy
Authors: Demsky Aaron
Published: November 2023

This paper examines the structure, message, and content of biblical genealogies in light of literary analysis and social anthropology. In particular, the focus is on the so-called “Table of Nations” in Genesis 10. My basic assumption is that most biblical genealogies are a literary genre employing various devices that carry a message using symbolic numbers, chiastic structure, and anticipation. These lists interact and supplement the narrative, sometimes as a foil to the story line. They are inserted at relevant points of change in the story of mankind from Adam and Eve to Joseph and his brothers. I even propose that these insertions are the earliest form of dividing the book of Genesis into installments, a precursor to weekly Torah readings and to the later division into chapters as in the printed text. The underlying message of this chapter is the value concept of the brotherhood of mankind stemming from one father—Noah. This innovative idea of universal kinship breaks with the common pagan view prevalent in antiquity that man’s place is to serve the gods and to have little or no personal identity. Note that the great urban cultures of ancient Egypt and Mesopotamia have left us no real records of family lineage other than the long king lists that reflect dynastic power. No doubt the importance of oral and written lineage stems from a tribal culture like that of the ancient Hebrews and their kindred. This overriding view even shaped the Nimrud pericope, describing his founding the urban centers of Babylon and Assyria. Genealogy became the natural medium expressing this message of universal kinship. Basic to understanding biblical genealogies is discerning two patterns of kinship, one, linear, stretching up to ten generations, and two, segmented genealogies, noting an eponymous “father” and his segmented offspring or wives. Our understanding of these structures in the Bible is shaped by the research of social anthropologists who studied oral genealogy among analphabetic tribes in Africa and the Middle East. I apply these observations and methodology in a detailed commentary on the Table of Nations.
Talking about Difference: Cross-Cultural Comparison and Prejudice in Anthropology and Beyond
Authors: White Bob W. , Gouin-Bonenfant Mathilde , Grégoire Anthony
Published: November 2023

In recent years, the question of “difference” has become a central feature of public debate and social concern, especially in the context of transnational migration. The underlying question that we attempt to answer in this article is: how can we talk about difference without reinforcing prejudice? Starting from the observation that perceptions and representations of difference have an impact on the way that individuals and groups interact with each other in increasingly diverse urban environments, we argue that a systemic approach to the analysis of intercultural situations gives us a unique window into emerging discourses and evolving norms about difference. After a brief historical overview of debates surrounding cross-cultural comparison in anthropology, we consider how various fields outside of anthropology have drawn inspiration from anthropology in order to gain a deeper understanding of intercultural dynamics in various professional settings. This article also examines several anthropological concepts that have been used as tools to theorize cross-cultural comparison, and how participants in a new research methodology use the systemic notion of “cultural variables” to resolve the basic paradox underlying pluralist philosophy and practice.
Simplification and Regularization Algorithm for Right-Angled Polygon Building Outlines with Jagged Edges
Authors: Kong Linghui , Qian Haizhong , Wu Yuqing , Niu Xinyu , Wang Di , Huang Zhekun
Published: November 2023

Building outlines are important for emergency response, urban planning, and change analysis and can be quickly extracted from remote sensing images and raster maps using deep learning technology. However, such building outlines often have irregular boundaries, redundant points, inaccurate positions, and unclear turns arising from variations in the image quality, the complexity of the surrounding environment, and the extraction methods used, impeding their direct utility. Therefore, this study proposes a simplification and regularization algorithm for right-angled polygon building outlines with jagged edges. First, the minimum bounding rectangle of the building outlines is established and populated with a square grid based on the smallest visible length principle. Overlay analysis is then applied to the grid and original buildings to extract the turning points of the outlines. Finally, the building orientation is used as a reference axis to sort the turning points and reconstruct the simplified building outlines. Experimentally, the proposed simplification method enhances the morphological characteristics of building outlines, such as parallelism and orthogonality, while considering simplification principles, such as the preservation of the direction, position, area, and shape of the building. The proposed algorithm provides a new simplification and regularization method for right-angled polygon building outlines with jagged edges.
Absence of Missense Variant Detection in Inherited Dysfibrinogenemia May Result from a Poor Raw Data Analysis Algorithm or Mosaicism
Authors: De Mazancourt Philippe , Mazoyer Elisabeth , Hormi Myriam , Hanss Michel
Published: November 2023

Variant identification underlying inherited dysfibrinogenemia quite exceptionally fails. We report on two dysfibrinogenemia cases whose underlying DNA variant could not be identified by Sanger analysis. These failures result from two distinct mechanisms. The first case involved raw signal overcorrection by a built-in software, and the second constituted the first description of mosaicism for one of the fibrinogen genes. This mosaicism was subsequently identified by next-generation sequencing reanalysis of the sample.
Genome-Wide Analysis of Cation/Proton Antiporter Family in Soybean (Glycine max) and Functional Analysis of GmCHX20a on Salt Response
Authors: Jia Qi , Song Junliang , Zheng Chengwen , Fu Jiahui , Qin Bin , Zhang Yongqiang , Liu Zhongjuan , Jia Kunzhi , Liang Kangjing , Lin Wenxiong , Fan Kai
Published: November 2023

Monovalent cation proton antiporters (CPAs) play crucial roles in ion and pH homeostasis, which is essential for plant development and environmental adaptation, including salt tolerance. Here, 68 CPA genes were identified in soybean, phylogenetically dividing into 11 Na+/H+ exchangers (NHXs), 12 K+ efflux antiporters (KEAs), and 45 cation/H+ exchangers (CHXs). The GmCPA genes are unevenly distributed across the 20 chromosomes and might expand largely due to segmental duplication in soybean. The GmCPA family underwent purifying selection rather than neutral or positive selections. The cis-element analysis and the publicly available transcriptome data indicated that GmCPAs are involved in development and various environmental adaptations, especially for salt tolerance. Based on the RNA-seq data, twelve of the chosen GmCPA genes were confirmed for their differentially expression under salt or osmotic stresses using qRT-PCR. Among them, GmCHX20a was selected due to its high induction under salt stress for the exploration of its biological function on salt responses by ectopic expressing in Arabidopsis. The results suggest that the overexpression of GmCHX20a increases the sensitivity to salt stress by altering the redox system. Overall, this study provides comprehensive insights into the CPA family in soybean and has the potential to supply new candidate genes to develop salt-tolerant soybean varieties.
Integrative Metabolome and Transcriptome Analyses Provide Insights into Carotenoid Variation in Different-Colored Peppers
Authors: Lv Junheng , Zhang Ruihao , Mo Yunrong , Zhou Huidan , Li Mengjuan , Wu Rui , Cheng Hong , Zhang Mingxian , Wang Huasu , Hua Wei , Deng Qiaoling , Zhao Kai , Deng Minghua
Published: November 2023

Carotenoids are important pigments in pepper fruits. The colors of each pepper are mainly determined by the composition and content of carotenoid. The ‘ZY’ variety, which has yellow fruit, is a natural mutant derived from a branch mutant of ‘ZR’ with different colors. ZY and ZR exhibit obvious differences in fruit color, but no other obvious differences in other traits. To investigate the main reasons for the formation of different colored pepper fruits, transcriptome and metabolome analyses were performed in three developmental stages (S1–S3) in two cultivars. The results revealed that these structural genes (PSY1, CRTISO, CCD1, CYP97C1, VDE1, CCS, NCED1 and NCED2) related to carotenoid biosynthesis were expressed differentially in the two cultivars. Capsanthin and capsorubin mainly accumulated in ZR and were almost non-existent in ZY. S2 is the fruit color-changing stage; this may be a critical period for the development of different color formation of ZY and ZR. A combination of transcriptome and metabolome analyses indicated that CCS, NCED2, AAO4, VDE1 and CYP97C1 genes were key to the differences in the total carotenoid content. These new insights into pepper fruit coloration may help to improve fruit breeding strategies.
The Antidepressant Activity of a Taurine-Containing Derivative of 4-Phenylpyrrolidone-2 in a Model of Chronic Unpredictable Mild Stress
Authors: Borozdenko Denis A. , Gonchar Darya I. , Bogorodova Vlada I. , Tarasenko Dmitri V. , Kramarova Evgeniya P. , Khovanova Svetlana S. , Golubev Yaroslav V. , Kiseleva Nina M. , Shmigol Tatiana A. , Ezdoglian Aiarpi A. , Sobyanin Konstantin A. , Negrebetsky Vadim V. , Baukov Yuri I.
Published: November 2023

This study investigates the therapeutic potential of a new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner’s chronic unpredictable mild stress model of male Wistar rats was used as a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group with saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light–dark box, were used to assess the animals’ conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to the intact animals. These results suggest that Compound I has reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.
Oxidative Stress in Xenograft Mouse Model Exposed to Dendrimers Decorated Polydopamine Nanoparticles and Targeted Chemo- and Photothermal Therapy
Authors: Witkowska Marta , Mrówczyński Radosław , Grześkowiak Bartosz , Miechowicz Izabela , Florek Ewa
Published: November 2023

Polydopamine (PDA)-based nanostructures are used for biomedical purposes. A hybrid drug nanocarrier based on a PDA decorated with polyamidoamine (PAMAM) dendrimers G 3.0 (DG3) followed by a connection with glycol (PEG) moieties, folic acid (FA), and drug doxorubicin (DOX) was used for combined chemo- and photothermal therapy (CT-PTT) of liver cancer. Oxidative stress plays a crucial role in the development of cancer, and PDA seems to have the ability to both donate and accept electrons. We investigated oxidative stress in organs by evaluating oxidative stress markers in vivo. In the liver, the level of reduced glutathione (GSH) was lower and the level of Trolox equivalent antioxidant capacity (TEAC) was higher in the group receiving doxorubicin encapsulated in PDA nanoparticles with phototherapy (PDA@DG3@PEG@FA@DOX + PTT) compared to the control group. The concentration of thiobarbituric acid reactive substances (TBARS) in livers, was higher in the group receiving PDA coated with PAMAM dendrimers and functionalized with PEG and FA (PDA@DG3@PEG@FA) than in other groups. Markers in the brain also showed lower levels of GSH in the PDA@DG3@PEG@FA group than in the control group. Markers of oxidative stress indicated changes in the organs of animals receiving PDA nanoparticles with PAMAM dendrimers functionalized with FA in CT-PTT of liver cancer under in vivo conditions. Our work will provide insights into oxidative stress, which can be an indicator of the toxic potential of PDA nanoparticles and provide new strategies to improve existing therapies.
Bioactive Polyketides from the Natural Complex of the Sea Urchin-Associated Fungi Penicillium sajarovii KMM 4718 and Aspergillus protuberus KMM 4747
Authors: Leshchenko Elena V. , Berdyshev Dmitrii V. , Yurchenko Ekaterina A. , Antonov Alexandr S. , Borkunov Gleb V. , Kirichuk Natalya N. , Chausova Viktoria E. , Kalinovskiy Anatoly I. , Popov Roman S. , Khudyakova Yuliya V. , Chingizova Ekaterina A. , Chingizov Artur R. , Isaeva Marina P. , Yurchenko Anton N.
Published: November 2023

The marine-derived fungal strains KMM 4718 and KMM 4747 isolated from sea urchin Scaphechinus mirabilis as a natural fungal complex were identified as Penicillium sajarovii and Aspergillus protuberus based on Internal Transcribed Spacer (ITS), partial β-tubulin (BenA), and calmodulin (CaM) molecular markers as well as an ribosomal polymerase two, subunit two (RPB2) region for KMM 4747. From the ethyl acetate extract of the co-culture, two new polyketides, sajaroketides A (1) and B (2), together with (2′S)-7-hydroxy-2-(2′-hydroxypropyl)-5-methylchromone (3), altechromone A (4), norlichexanthone (5), griseoxanthone C (6), 1,3,5,6-tetrahydroxy-8-methylxanthone (7), griseofulvin (8), 6-O-desmethylgriseofulvin (9), dechlorogriseofulvin (10), and 5,6-dihydro-4-methyl-2H-pyran-2-one (11) were identified. The structures of the compounds were elucidated using spectroscopic analyses. The absolute configurations of the chiral centers of sajaroketides A and B were determined using time-dependent density functional theory (TDDFT)-based calculations of the Electronic Circular Dichroism (ECD) spectra. The inhibitory effects of these compounds on urease activity and the growth of Staphylococcus aureus, Escherichia coli, and Candida albicans were observed. Sajaroketide A, altechromone A, and griseofulvin showed significant cardioprotective effects in an in vitro model of S. aureus-induced infectious myocarditis.
Galgravin Isolated from Piper kadsura Ameliorates Lipopolysaccharide (LPS)-Induced Endotoxemia in Mice
Authors: Ou Shih-Ming , Hsu Yin-Chieh , Fu Shu-Ling , Lin Lie-Chwen , Lin Chao-Hsiung
Published: November 2023

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.
High Filamin a Expression in Adrenocortical Carcinomas Is Associated with a Favourable Tumour Behaviour: A European Multicentric Study
Authors: Catalano Rosa , Altieri Barbara , Angelousi Anna , Arosio Maura , Bravi Francesca , Canu Letizia , Croci Giorgio A. , Detomas Mario , Esposito Emanuela , Ferrante Emanuele , Ferrero Stefano , Fuss Carmina T. , Kaltsas Gregory , Kimpel Otilia , Landwehr Laura-Sophie , Luconi Michaela , Morelli Valentina , Nesi Gabriella , Nozza Emma , Sbiera Silviu , Serban Andreea L. , Ronchi Cristina L. , Mantovani Giovanna , Peverelli Erika
Published: November 2023

The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs. We found that 71.4% of ACCs did not express FLNA, whereas FLNA absence was a rare event in ACAs (15.4%, p < 0.001 vs. ACCs). In addition, the expression of FLNA was associated with a less aggressive tumour behaviour in ACCs. Indeed, the subgroup of ACCs with high FLNA showed a lower ENSAT stage, Weiss score, and S-GRAS score compared to ACCs with low FLNA expression (p < 0.05). Moreover, patients with high FLNA had a longer overall survival than those with low FLNA (p < 0.05). In conclusion, our data suggest that FLNA may represent a “protective” factor in ACCs, and the integration of FLNA immunohistochemical expression in ACC tissues along with other clinical and molecular markers could be helpful to improve diagnostic accuracy and prognosis prediction in ACCs.
Efficacy and Safety of Statin Treatment in Children with Familial Hypercholesterolemia: Outcomes of 20 Years of Experience
Authors: Motkowski Radosław , Abramowicz Paweł , Kubalska Jolanta , Mikołuć Bożena , Konstantynowicz Jerzy
Published: November 2023

Background: The objective of this retrospective cohort study was to present the experience of 20-year-long comprehensive care of pediatric patients with familial hypercholesterolemia (FH) in a single academic center. Methods and Results: The study included 84 children aged 1–18 years with FH. For the whole study group, 535 medical visits were recorded. The mean follow-up period was 33.6 months. Molecular testing performed in 55 children (65%) provided genetic confirmation of the diagnosis in 36 children (43%). Twenty-seven children (32%) were treated pharmacologically with statins. Follow-up during the treatment averaged 29 months. Treatment with statins was associated with a mean reduction in total cholesterol and LDL-cholesterol levels of 24 and 33% from the baseline. Symptoms of statin intolerance occurred incidentally and did not require amendment in the treatment protocol. Significantly higher values of body weight, height, and BMI were found only among girls older than 10 years who were treated with statins. Conclusions: These data confirm a high efficacy and a good safety profile of statin treatment in children with FH, demonstrating no harm to physical development. However, there is a need for further cause-and-effect research regarding associations between long-term treatment with low-cholesterol, low-fat diets, statin therapy, and excessive weight gain.
The Interplay between Cannabinoid Receptors and Microglia in the Pathophysiology of Alzheimer’s Disease
Authors: Ferrisi Rebecca , Gado Francesca , Ricardi Caterina , Polini Beatrice , Manera Clementina , Chiellini Grazia
Published: November 2023

Alzheimer’s disease (AD) is characterized by massive neuronal death, brain atrophy, and loss of neurons and synapses, which all lead to a progressive cognitive decline. Neuroinflammation has been recently identified as one of the main causes of AD progression, and microglia cells are considered to have a central role in this process. Growing evidence suggests that cannabinoids may be used as preventive treatment for AD. An altered expression of the endocannabinoids (eCBs) and their receptors (CBRs) is reported in several neurodegenerative disorders, including AD. Moreover, the modulation of CBRs demonstrated neuroprotective effects in reducing aggregated protein deposition, suggesting the therapeutic potential of natural and synthetic CBR ligands in the treatment of neurodegenerative proteinopathies. Here, we review the current knowledge regarding the involvement of CBRs in the modulation of microglia activation phenotypes, highlighting the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, like AD. We also provide an overview of recently developed candidate drugs targeting CBRs that may afford a new innovative strategy for the treatment and management of AD.
The Effect of Personalized Shoe Insoles on Parkinson’s Disease Subjects: A Triple-Blind Randomized Controlled Trial
Authors: Pollet Joel , Buraschi Riccardo , Ranica Giorgia , Pancera Simone , Anastasi Denise , Fazio Rossella , Monteleone Serena , Lena Eleonora , Floridi Valeria , Zucchini Franco , Falso Maurizio Vincenzo
Published: November 2023

Subjects with Parkinson’s Disease (PD) display different motor and non-motor symptoms. Different therapies have been shown to be effective, such as plantar foot stimulation, which has proved to be effective for motor symptoms. Different stimulation methods were proposed and tested through specific devices, or insoles. Our aim was to assess the effect of a newly designed custom-made insole called PRO-STEP compared with a flat sham insole on subjects with PD. Subjects were randomized 1:1 into two arms and were asked to wear PRO-STEP or sham insoles for at least 6 h per day for 10 weeks. Participants were evaluated at four timepoints. Forty-two subjects were randomly assigned to the PRO-STEP (EG) or sham group (SG). The comparison of the EG and SG without and with insoles (T0–T1) did not show significant differences in the TUG time and in the 10MWT gait parameters. At T1, T2, and T3 TUG time, BBS, SF12-MC, and SF12-PC did not show significant differences. The satisfaction level with the PRO-STEP or sham insoles was high in both groups. PD patients were satisfied with PRO-STEP insoles; however, plantar foot stimulation is not effective from a functional perspective. Future studies should consider possible modifications to the proposed stimulation to improve its effectiveness in patients with PD.
Can the Modified Frailty Index (mFI) Predict Intraoperative and Postoperative Complications in Older Women with Endometrial Cancer Undergoing Laparoscopic or Robotic Surgery? A Multicenter Observational Study
Authors: Schipa Chiara , Ripa Matteo , Gallotta Valerio , Russo Andrea , Polidori Lorenzo , Fanfani Francesco , Capomacchia Filippo Maria , Corrado Giacomo , Vizza Enrico , Perrone Anna Myriam , Mereu Liliana , Cela Vito , Legge Francesco , Hilaris Georgios , Pasciuto Tina , D’Indinosante Marco , La Fera Eleonora , Certelli Camilla , Bruno Valentina , Kogeorgos Stylianos , De Iaco Pierandrea , Lathouras Konstantinos , Sollazzi Liliana , Scambia Giovanni , Aceto Paola
Published: November 2023

Background: This study aims to evaluate the strength of the association between frailty and intraoperative/postoperative complications in patients undergoing minimally invasive surgery (MIS) for endometrial cancer. Methods: In this retrospective observational multicenter cohort study, frailty was defined beforehand by a modified frailty index (mFI) score of ≥3. Multiple logistic regressions were performed to investigate possible preoperative predictors—including frailty, age, and body mass index—of intraoperative and early (within 30 days from surgery) or delayed (beyond 30 days from surgery) postoperative complications. Results: The study involved 577 women, of whom 6.9% (n = 40) were frail with an mFI ≥ 3, while 93.1% (n = 537) were non-frail with an mFI of 0–2. Frail women had a significantly higher rate of intraoperative complications (7.5% vs. 1.7%, p = 0.01), with odds 4.54 times greater (95% CI: 1.18–17.60, p = 0.028). There were no differences in the rate of early postoperative complications (15% vs. 6.9%, p = 0.06) and delayed postoperative complications (2.5% vs. 3.9%, p = 0.65) for frail versus non-frail patients. The odds of early postoperative complications increased by 0.7% (95% CI: 1.00–1.15) for every one-unit increase in age (p = 0.032). Conclusions: Frailty was associated with a significantly higher risk of intraoperative complications in older women undergoing MIS for endometrial cancer. Likewise, increasing age was an independent predictor of early postoperative complications. Our findings support the practice of assessing frailty before surgery to optimize perioperative management in this patient population.
Comparison of Immediate, Medium, and Long-Term Postoperative Results of Open Surgery and Fenestrated/Branched Stent Grafts for Extended Thoracoabdominal Aortic Aneurysms
Authors: Cochennec Frédéric , Couture Thibault , Chiche Laurent
Published: November 2023

The optimal surgical treatment for extended thoracoabdominal aortic aneurysms (TAAAs) is still a matter of debate. The historical treatment is open repair (OR), but over the past fifteen years, endovascular strategies have gained widespread acceptance. Although several endovascular techniques have been described for the treatment of TAAAs, fenestrated and branched stent grafts (F/BEVARs) are the most frequently used and best documented. They have become the first-line treatment for both high- and moderate-risk surgical patients in most vascular centers. However, no randomized study comparing OR and F/BEVAR has been published, and decision-making is mainly based on the physician’s preference and/or hospital expertise. The objective of this manuscript is to provide an overview of current comparative data for OR and F/BEVAR.
From Bedside to Diagnosis: The Role of Ocular Fundus in Systemic Infections
Authors: Visioli Giacomo , Zeppieri Marco , Iannucci Valeria , Manni Priscilla , Albanese Giuseppe Maria , Salati Carlo , Spadea Leopoldo , Pirraglia Maria Pia
Published: November 2023

In this comprehensive review, we delve into the significance of the ocular fundus examination in diagnosing and managing systemic infections at the bedside. While the utilization of advanced ophthalmological diagnostic technologies can present challenges in bedside care, especially for hospitalized patients confined to their beds or during infection outbreaks, the ocular fundus examination often emerges as an essential, and sometimes the only practical, diagnostic tool. Recent discussions have highlighted that the role of an ocular fundus examination might not always be advocated as a routine diagnostic procedure. With this context, we introduce a decision tree tailored for assessing the ocular fundus in inpatients with systemic infections. We also present an overview of systemic infections that impact the eye and elucidate key signs detectable through a bedside ocular fundus examination. Targeted primarily at non-ophthalmology clinicians, this review seeks to offer a comprehensive insight into a multifaceted approach and the enhancement of patient clinical outcomes.
A Meta-Analysis of the Global Stillbirth Rates during the COVID-19 Pandemic
Authors: Mohan Manoj , Appiah-Sakyi Kwabena , Oliparambil Ashok , Pullattayil Abdul Kareem , Lindow Stephen W. , Ahmed Badreldeen , Konje Justin C.
Published: November 2023

COVID-19 has been shown to have variable adverse effects on pregnancy. Reported data on stillbirth rates during the pandemic have, however, been inconsistent—some reporting a rise and others no change. Knowing the precise impact of COVID-19 on stillbirths should help with the planning and delivery of antenatal care. Our aim was, therefore, to undertake a meta-analysis to determine the impact of COVID-19 on the stillbirth rate. Databases searched included PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science, with no language restriction. Publications with stillbirth data on women with COVID-19, comparing stillbirth rates in COVID-19 and non-COVID-19 women, as well as comparisons before and during the pandemic, were included. Two independent reviewers extracted data separately and then compared them to ensure the accuracy of extraction and synthesis. Where data were incomplete, authors were contacted for additional information, which was included if provided. The main outcome measures were (1) stillbirth (SB) rate in pregnant women with COVID-19, (2) stillbirth rates in pregnant women with and without COVID-19 during the same period, and (3) population stillbirth rates in pre-pandemic and pandemic periods. A total of 29 studies were included in the meta-analysis; from 17 of these, the SB rate was 7 per 1000 in women with COVID-19. This rate was much higher (34/1000) in low- and middle-income countries. The odds ratio of stillbirth in COVID-19 compared to non-COVID-19 pregnant women was 1.89. However, there was no significant difference in population SB between the pre-pandemic and pandemic periods. Stillbirths are an ongoing global concern, and there is evidence that the rate has increased during the COVID-19 pandemic, but mostly in low- and middle-income countries. A major factor for this is possibly access to healthcare during the pandemic. Attention should be focused on education and the provision of high-quality maternity care, such as face-to-face consultation (taking all the preventative precautions) or remote appointments where appropriate.
Factors Associated with Smokers Attending More Than One Smoking Cessation Clinic Visit
Authors: Kwon Oh Beom , Jung Chihoon , Kim Auk , Byeon Gihwan , Lee Seung-Joon , Kim Woo Jin
Published: November 2023

Smoking remains a primary cause of cancers, cardiovascular and respiratory diseases and death. Globally, efforts have been made to reduce smoking rates, but the addictive nature of nicotine, a key component of tobacco, makes cessation challenging for smokers. Medical interventions including medical advice and pharmacotherapies are effective methods for smoking cessation. The frequency of medical interventions correlates with success in smoking cessation. This study aims to compare the characteristics of the patients who visited the smoking cessation clinic once with those who visited more than once, in order to identify factors that are associated with repeat clinic visits. A total of 81 patients who have visited the smoking cessation clinic in Kangwon National University Hospital were included. Patients answered the questionnaire at their first visit. If the patient visited only once, the outcome was defined as negative and if the patient visited more than once, the outcome was defined as positive. The proportion of patients who answered “within 5 min” to the Fagerstrom Test for Nicotine Dependence’s (FTND) 1st question and answered “yes” to the FTND’s 6th question was higher in the negative outcome group. In the logistic regression, patients who had withdrawal symptoms previously were associated with positive outcomes (adjusted OR 3.466, 95% CI 1.088–11.034 and p value = 0.0354). Withdrawal symptoms during previous attempts were positively related to visiting the clinic more than once.