bluuebunny/crossref_metadata_2025 huggingface dataset:
Excellence in Heart Failure: A Multidisciplinary Program on Heart Failure Management for Improved Patient Outcome
Authors: Sousa Olga , Ponte Marta , Caeiro Daniel , Pereira Eulália , Silva Marisa , Pestana Sandra , Braga Pedro , Fontes-Carvalho Ricardo
Published: December 2023

Chronic heart failure (HF) is the 21st-century cardiovascular epidemic, marked by recurrent hospitalizations and high mortality rates, and represents a considerable burden on Western societies. The complex care demands of HF patients require multidisciplinary approaches, aligning with contemporary guidelines. Accordingly, the Excellence in Heart Failure Program, implemented in Portuguese tertiary hospitals, aims to establish multidisciplinary HF outpatient clinics in Portugal, improving patients’ clinical outcomes. Herein, the results of its pilot project are presented, showing that the implementation of the multidisciplinary clinic resulted in a minimal number of hospitalizations and emergency visits, with only one rehospitalization reported. In addition, patients in the Program experienced significant improvements in ejection fraction (EF) and NT-proBNP levels. Despite the limited power of the sample, these findings underscore the effectiveness of the Program in the management of Portuguese HF patients, particularly in the early discharge period after heart failure, when patients are most vulnerable.
Effects of Nitrogen Source on Mineral Element, Phytochemical Content, and Antioxidant Activity of Short-Day Onion (Allium cepa) Bulbs
Authors: Simelane Mzwakhile Petros Zakhe , Soundy Puffy , Amoo Stephen O. , Maboko Martin Makgose
Published: December 2023

Onion (Allium cepa) is one of the world’s most consumed, nutrient-dense foods, low in calories and containing a rich amount of major bioactive compounds, vitamins, and minerals. The purpose of this study was to determine the influence of different nitrogen (N) fertilizer sources on the nutritional and phytochemical qualities of short-day onions. A white-type onion (cv. Texas Grano) was subjected to different fertilizer application treatments, namely (i) pre-plant base application of 80 kg ha−1 N from CaCN2, alone or in combination with (ii) top-dressing with 50 kg ha−1 N from limestone ammonium nitrate (LAN), or (iii) top-dressing with 50 kg ha−1 N from urea, (iv) pre-plant base application of 80 kg ha−1 N from LAN and top-dressing with 50 kg ha−1 N from LAN, (v) pre-plant base application of 80 kg ha−1 N from urea and top-dressing with 50 kg ha−1 N from urea, and (vi) 0 kg ha−1 N. Pre-plant application of CaCN2 (80 kg ha−1 N) outperformed standard onion fertilizers, urea (130 kg ha−1 N) and LAN (130 kg ha−1 N), significantly enhancing total phenolic content, antioxidant activity, and calcium (Ca) and potassium (K) content in onion bulbs. Applying 50 kg ha−1 N from urea as top-dressing with the pre-plant application of CaCN2 (80 kg ha−1 N) elevated total phenolics (5.48 mg GAE g−1) and flavonoids (0.741 mg CE g−1) in the onion bulbs. The highest antioxidant activity (55.9%) and free radical scavenging activity (26.3%) were achieved with top-dressing 50 kg ha−1 N from LAN following CaCN2 pre-plant application. Application of CaCN2 + urea also significantly increased onion bulb potassium (2335 mg kg−1) and calcium (828 mg kg−1) contents, while CaCN2 combined with LAN improved magnesium (123.3 mg kg−1) content. This study recommends pre-plant CaCN2, top-dressed with either LAN or urea, for improved phytochemical components, antioxidant activities, and certain mineral content in onion bulbs. These findings present a practical approach for cultivating nutrient-rich and phytochemically abundant onion bulbs, promoting improved human health.
The Importance of Gender-Sensitive Health Care in the Context of Pain, Emergency and Vaccination: A Narrative Review
Authors: Graf Joachim , Simoes Elisabeth , Kranz Angela , Weinert Konstanze , Abele Harald
Published: December 2023

So far, health care has been insufficiently organized in a gender-sensitive way, which makes the promotion of care that meets the needs of women and men equally emerge as a relevant public health problem. The aim of this narrative review was to outline the need for more gender-sensitive medical care in the context of pain, emergency care and vaccinations. In this narrative review, a selective search was performed in Pubmed, and the databases of the World Health Organization (WHO), the European Institute for Gender Equality and the German Federal Ministry of Health were searched. Study data indicate that there are differences between men and women with regard to the ability to bear pain. On the other hand, socially constructed role expectations in pain and the communication of these are also relevant. Studies indicate that women receive adequate pain medication less often than men with a comparable pain score. Furthermore, study results indicate that the female gender is associated with an increased risk of inadequate emergency care. In terms of vaccine provision, women are less likely than men to utilize or gain access to vaccination services, and there are gender-sensitive differences in vaccine efficacy and safety. Sensitization in teaching, research and care is needed to mitigate gender-specific health inequalities.
Multiscale Feature Extraction by Using Convolutional Neural Network: Extraction of Objects from Multiresolution Images of Urban Areas
Authors: Fan Ching-Lung
Published: December 2023

The emergence of deep learning-based classification methods has led to considerable advancements and remarkable performance in image recognition. This study introduces the Multiscale Feature Convolutional Neural Network (MSFCNN) for the extraction of complex urban land cover data, with a specific emphasis on buildings and roads. MSFCNN is employed to extract multiscale features from three distinct image types—Unmanned Aerial Vehicle (UAV) images, high-resolution satellite images (HR), and low-resolution satellite images (LR)—all collected within the Fengshan District of Kaohsiung, Taiwan. The model in this study demonstrated remarkable accuracy in classifying two key land cover categories. Its success in extracting multiscale features from different image resolutions. In the case of UAV images, MSFCNN achieved an accuracy rate of 91.67%, with a Producer’s Accuracy (PA) of 93.33% and a User’s Accuracy (UA) of 90.0%. Similarly, the model exhibited strong performance with HR images, yielding accuracy, PA, and UA values of 92.5%, 93.33%, and 91.67%, respectively. These results closely align with those obtained for LR imagery, which achieved respective accuracy rates of 93.33%, 95.0%, and 91.67%. Overall, the MSFCNN excels in the classification of both UAV and satellite images, showcasing its versatility and robustness across various data sources. The model is well suited for the task of updating cartographic data related to urban buildings and roads.
Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System
Authors: Cao Yi-Yang , Wu Ling-Ling , Li Xiao-Nan , Yuan Yu-Lian , Zhao Wan-Wei , Qi Jing-Xuan , Zhao Xu-Yu , Ward Natalie , Wang Jiao
Published: December 2023

Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.
The Functions of Pt-DIC and Pt-Lamin B in Spermatogenesis of Portunus trituberculatus
Authors: Wang Shuo-Yue , Xiang Qiu-Meng , Zhu Jun-Quan , Mu Chang-Kao , Wang Chun-Lin , Hou Cong-Cong
Published: December 2023

Cytoplasmic Dynein is a multiple-subunit macromolecular motor protein involved in the transport process of cells. The Dynein intermediate chain (DIC) is one of the subunits of Dynein-1. In our previous studies, we showed that Pt-DIC may play an important role in the nuclear deformation of spermiogenesis in Portunus trituberculatus. Lamin B is essential for maintaining nuclear structure and functions. Surprisingly, Pt-Lamin B was expressed not only in the perinucleus but also in the pro-acrosome during spermiogenesis in P. trituberculatus. Studies have also shown that Dynein-1 can mediate the transport of Lamin B in mammals. Thus, to study the relationship of Pt-DIC and Pt-Lamin B in the spermatogenesis of P. trituberculatus, we knocked down the Pt-DIC gene in P. trituberculatus by RNAi. The results showed that the distribution of Pt-DIC and Pt-Lamin B in spermiogenesis was abnormal, and the colocalization was weakened. Moreover, we verified the interaction of Pt-DIC and Pt-Lamin B via coimmunoprecipitation. Therefore, our results suggested that both Pt-DIC and Pt-Lamin B were involved in the spermatogenesis of P. trituberculatus, and one of the functions of Dynein-1 is to mediate the transport of Lamin B in the spermiogenesis of P. trituberculatus.
Genome-Wide Identification and Expression Analysis of the Stearoyl-Acyl Carrier Protein Δ9 Desaturase Gene Family under Abiotic Stress in Barley
Authors: Ding Mingyu , Zhou Danni , Ye Yichen , Wen Shuting , Zhang Xian , Tian Quanxiang , Zhang Xiaoqin , Mou Wangshu , Dang Cong , Fang Yunxia , Xue Dawei
Published: December 2023

Stearoyl-acyl carrier protein (ACP) Δ9 desaturase (SAD) is a critical fatty acid dehydrogenase in plants, playing a prominent role in regulating the synthesis of unsaturated fatty acids (UFAs) and having a significant impact on plant growth and development. In this study, we conducted a comprehensive genomic analysis of the SAD family in barley (Hordeum vulgare L.), identifying 14 HvSADs with the FA_desaturase_2 domain, which were divided into four subgroups based on sequence composition and phylogenetic analysis, with members of the same subgroup possessing similar genes and motif structures. Gene replication analysis suggested that tandem and segmental duplication may be the major reasons for the expansion of the SAD family in barley. The promoters of HvSADs contained various cis-regulatory elements (CREs) related to light, abscisic acid (ABA), and methyl jasmonate (MeJA). In addition, expression analysis indicated that HvSADs exhibit multiple tissue expression patterns in barley as well as different response characteristics under three abiotic stresses: salt, drought, and cold. Briefly, this evolutionary and expression analysis of HvSADs provides insight into the biological functions of barley, supporting a comprehensive analysis of the regulatory mechanisms of oil biosynthesis and metabolism in plants under abiotic stress.
Disparity in the Influence of Implant Provisional Materials on Human Gingival Fibroblasts with Different Phases of Cell Settlement: An In Vitro Study
Authors: Matsuura Takanori , Stavrou Stella , Komatsu Keiji , Cheng James , Pham Alisa , Ferreira Stephany , Baba Tomomi , Chang Ting-Ling , Chao Denny , Ogawa Takahiro
Published: December 2023

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens—bis-acrylic 1 and 2, flowable and bulk–fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control—were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20–30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk–fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.
Expression Dynamics Indicate Potential Roles of KIF17 for Nuclear Reshaping and Tail Formation during Spermiogenesis in Phascolosoma esculenta
Authors: Pan Yue , Wang Jingqian , Gao Xinming , Du Chen , Hou Congcong , Tang Daojun , Zhu Junquan
Published: December 2023

Kinesin family member17 (KIF17), a homologous dimer of the kinesin-2 protein family, has important microtubule-dependent and -independent roles in spermiogenesis. Little is known about KIF17 in the mollusk, Phascolosoma esculenta, a newly developed mariculture species in China. Here, we cloned the open reading frame of Pe-kif17 and its related gene, Pe-act, and performed bioinformatics analysis on both. Pe-KIF17 and Pe-ACT are structurally conserved, indicating that they may be functionally conserved. The expression pattern of kif17/act mRNA performed during spermiogenesis revealed their expression in diverse tissues, with the highest expression level in the coelomic fluid of P. esculenta. The expressions of Pe-kif17 and Pe-act mRNA were relatively high during the breeding season (July–September), suggesting that Pe-KIF17/ACT may be involved in spermatogenesis, particularly during spermiogenesis. Further analysis of Pe-kif17 mRNA via fluorescence in situ hybridization revealed the continuous expression of this mRNA during spermiogenesis, suggesting potential functions in this process. Immunofluorescence showed that Pe-KIF17 co-localized with α-tubulin and migrated from the perinuclear cytoplasm to one side of the spermatid, forming the sperm tail. Pe-KIF17 and Pe-ACT also colocalized. KIF17 may participate in spermiogenesis of P. esculenta, particularly in nuclear reshaping and tail formation by interacting with microtubule structures similar to the manchette. Moreover, Pe-KIF17 with Pe-ACT is also involved in nuclear reshaping and tail formation in the absence of microtubules. This study provides evidence for the role of KIF17 during spermiogenesis and provides theoretical data for studies of the reproductive biology of P. esculenta. These findings are important for spermatogenesis in mollusks.
Role of Luteolin as Potential New Therapeutic Option for Patients with Glioblastoma through Regulation of Sphingolipid Rheostat
Authors: Navone Stefania Elena , Guarnaccia Laura , Rizzaro Massimiliano D. , Begani Laura , Barilla Emanuela , Alotta Giovanni , Garzia Emanuele , Caroli Manuela , Ampollini Antonella , Violetti Aniello , Gervasi Noreen , Campanella Rolando , Riboni Laura , Locatelli Marco , Marfia Giovanni
Published: December 2023

Glioblastoma (GBM) is the most aggressive brain tumor, still considered incurable. In this study, conducted on primary GBM stem cells (GSCs), specifically selected as the most therapy-resistant, we examined the efficacy of luteolin, a natural flavonoid, as an anti-tumoral compound. Luteolin is known to impact the sphingolipid rheostat, a pathway regulated by the proliferative sphingosine-1-phosphate (S1P) and the proapoptotic ceramide (Cer), and implicated in numerous oncopromoter biological processes. Here, we report that luteolin is able to inhibit the expression of SphK1/2, the two kinases implicated in S1P formation, and to increase the expression of both SGPL1, the lyase responsible for S1P degradation, and CERS1, the ceramide synthase 1, thus shifting the balance toward the production of ceramide. In addition, luteolin proved to decrease the expression of protumoral signaling as MAPK, RAS/MEK/ERK and PI3K/AKT/mTOR and cyclins involved in cell cycle progression. In parallel, luteolin succeeded in upregulation of proapoptotic mediators as caspases and Bcl-2 family and cell cycle controllers as p53 and p27. Furthermore, luteolin determined the shutdown of autophagy contributing to cell survival. Overall, our data support the use of luteolin as add-on therapy, having demonstrated a good ability in impairing GSC viability and survival and increasing cell sensitivity to TMZ.
PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model
Authors: Lin Yu-Kai , Hsiao Lien-Cheng , Wu Mei-Yao , Chen Yun-Fang , Lin Yen-Nien , Chang Chia-Ming , Chung Wei-Hsin , Chen Ke-Wei , Lu Chiung-Ray , Chen Wei-Yu , Chang Shih-Sheng , Shyu Woei-Cheang , Lee An-Sheng , Chen Chu-Huang , Jeng Long-Bin , Chang Kuan-Cheng
Published: December 2023

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure–volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure–volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.
Perfluorooctanoic Acid (PFOA) Exposure Compromises Fertility by Affecting Ovarian and Oocyte Development
Authors: Zhang Han , Han Lulu , Qiu Lijun , Zhao Bo , Gao Yang , Chu Zhangjie , Dai Xiaoxin
Published: December 2023

PFOA, a newly emerging persistent organic pollutant, is widely present in various environmental media. Previous reports have proved that PFOA exposure can accumulate in the ovary and lead to reproductive toxicity in pregnant mice. However, the potential mechanism of PFOA exposure on fertility remains unclear. In this study, we explore how PFOA compromises fertility in the zebrafish. The data show that PFOA (100 mg/L for 15 days) exposure significantly impaired fertilization and hatching capability. Based on tissue sections, we found that PFOA exposure led to ovarian damage and a decrease in the percentage of mature oocytes. Moreover, through in vitro incubation, we determined that PFOA inhibits oocyte development. We also sequenced the transcriptome of the ovary of female zebrafish and a total of 284 overlapping DEGs were obtained. Functional enrichment analysis showed that 284 overlapping DEGs function mainly in complement and coagulation cascades signaling pathways. In addition, we identified genes that may be associated with immunity, such as LOC108191474 and ZGC:173837. We found that exposure to PFOA can cause an inflammatory response that can lead to ovarian damage and delayed oocyte development.
Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients
Authors: Marques Inês Soares , Tavares Valéria , Savva-Bordalo Joana , Rei Mariana , Liz-Pimenta Joana , de Melo Inês Guerra , Assis Joana , Pereira Deolinda , Medeiros Rui
Published: December 2023

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann–Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.
An Integrated Multi-Omics Analysis Identifying Immune Subtypes of Pancreatic Cancer
Authors: Su Yongcheng , Wang Fen , Lei Ziyu , Li Jiangquan , Ma Miaomiao , Yan Ying , Zhang Wenqing , Chen Xiaolei , Xu Beibei , Hu Tianhui
Published: December 2023

Limited studies have explored novel pancreatic cancer (PC) subtypes or prognostic biomarkers based on the altered activity of relevant signaling pathway gene sets. Here, we employed non-negative matrix factorization (NMF) to identify three immune subtypes of PC based on C7 immunologic signature gene set activity in PC and normal samples. Cluster 1, the immune-inflamed subtype, showed a higher response rate to immune checkpoint blockade (ICB) and had the lowest tumor immune dysfunction and exclusion (TIDE) scores. Cluster 2, the immune-excluded subtype, exhibited strong associations with stromal activation, characterized by elevated expression levels of transforming growth factor (TGF)-β, cell adhesion, extracellular matrix remodeling, and epithelial-to-mesenchymal transition (EMT) related genes. Cluster 3, the immune-desert subtype, displayed limited immune activity. For prognostic prediction, we developed an immune-related prognostic risk model (IRPM) based on four immune-related prognostic genes in pancreatic cancer, RHOF, CEP250, TSC1, and KIF20B. The IRPM demonstrated excellent prognostic efficacy and successful validation in an external cohort. Notably, the key gene in the prognostic model, RHOF, exerted significant influence on the proliferation, migration, and invasion of pancreatic cancer cells through in vitro experiments. Furthermore, we conducted a comprehensive analysis of somatic mutational landscapes and immune landscapes in PC patients with different IRPM risk scores. Our findings accurately stratified patients based on their immune microenvironment and predicted immunotherapy responses, offering valuable insights for clinicians in developing more targeted clinical strategies.
The Complex Interplay between the Gut Microbiome and Osteoarthritis: A Systematic Review on Potential Correlations and Therapeutic Approaches
Authors: Marchese Laura , Contartese Deyanira , Giavaresi Gianluca , Di Sarno Laura , Salamanna Francesca
Published: December 2023

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE’s risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients.
Advances in Nucleic Acid Research: Exploring the Potential of Oligonucleotides for Therapeutic Applications and Biological Studies
Authors: Moccia Maria , Pascucci Barbara , Saviano Michele , Cerasa Maria Teresa , Terzidis Michael A. , Chatgilialoglu Chryssostomos , Masi Annalisa
Published: December 2023

In recent years, nucleic acids have emerged as powerful biomaterials, revolutionizing the field of biomedicine. This review explores the multifaceted applications of nucleic acids, focusing on their pivotal role in various biomedical applications. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), possess unique properties such as molecular recognition ability, programmability, and ease of synthesis, making them versatile tools in biosensing and for gene regulation, drug delivery, and targeted therapy. Their compatibility with chemical modifications enhances their binding affinity and resistance to degradation, elevating their effectiveness in targeted applications. Additionally, nucleic acids have found utility as self-assembling building blocks, leading to the creation of nanostructures whose high order underpins their enhanced biological stability and affects the cellular uptake efficiency. Furthermore, this review delves into the significant role of oligonucleotides (ODNs) as indispensable tools for biological studies and biomarker discovery. ODNs, short sequences of nucleic acids, have been instrumental in unraveling complex biological mechanisms. They serve as probes for studying gene expression, protein interactions, and cellular pathways, providing invaluable insights into fundamental biological processes. By examining the synergistic interplay between nucleic acids as powerful biomaterials and ODNs as indispensable tools for biological studies and biomarkers, this review highlights the transformative impact of these molecules on biomedical research. Their versatile applications not only deepen our understanding of biological systems but also are the driving force for innovation in diagnostics and therapeutics, ultimately advancing the field of biomedicine.
Considerations about Cytotoxicity of Resin-Based Composite Dental Materials: A Systematic Review
Authors: Wiertelak-Makała Kacper , Szymczak-Pajor Izabela , Bociong Kinga , Śliwińska Agnieszka
Published: December 2023

The dental material industry is rapidly developing resin-based composites (RBCs), which find widespread use in a variety of clinical settings. As such, their biocompatibility has gained increasing interest. This literature review presents a summary of research into the cytotoxicity of methacrylate-based composites published from 2017 to 2023. Subject to analysis were 14 in vitro studies on human and murine cell lines. Cytotoxicity in the included studies was measured via MTT assay, LDH assay, and WST-1 assay. The QUIN Risk of Bias Tool was performed to validate the included studies. Included studies (based entirely on the results of in vitro studies) provide evidence of dose- and time-dependent cytotoxicity of dental resin-based composites. Oxidative stress and the depletion of cellular glutathione (GSH) were suggested as reasons for cytotoxicity. Induction of apoptosis by RBCs was indicated. While composites remain the golden standard of dental restorative materials, their potential cytotoxicity cannot be ignored due to direct long-term exposure. Further in vitro investigations and clinical trials are required to understand the molecular mechanism of cytotoxicity and produce novel materials with improved safety profiles.
Preliminary Study on the Formation Mechanism of Malformed Sweet Cherry (Prunus avium L.) Fruits in Southern China Using Transcriptome and Metabolome Data
Authors: Zhang Wangshu , Xu Yue , Jing Luyang , Jiang Baoxin , Wang Qinghao , Wang Yuxi
Published: December 2023

Gibberellin (GA) is an important plant hormone that is involved in various physiological processes during plant development. Sweet cherries planted in southern China have always encountered difficulty in bearing fruit. In recent years, gibberellin has successfully solved this problem, but there has also been an increase in malformed fruits. This study mainly explores the mechanism of malformed fruit formation in sweet cherries. By analyzing the synthesis pathway of gibberellin using metabolomics and transcriptomics, the relationship between gibberellin and the formation mechanism of deformed fruit was preliminarily determined. The results showed that the content of GA3 in malformed fruits was significantly higher than in normal fruits. The differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were mainly enriched in pathways such as “plant hormone signal transduction”, “diterpenoid biosynthesis”, and “carotenoid biosynthesis”. Using Quantitative Real-Time Reverse Transcription PCR (qRT-PCR) analysis, the gibberellin hydrolase gene GA2ox and gibberellin synthase genes GA20ox and GA3ox were found to be significantly up-regulated. Therefore, we speculate that the formation of malformed fruits in sweet cherries may be related to the accumulation of GA3. This lays the foundation for further research on the mechanism of malformed sweet cherry fruits.
Profiling Novel Quinuclidine-Based Derivatives as Potential Anticholinesterase Drugs: Enzyme Inhibition and Effects on Cell Viability
Authors: Žunec Suzana , Vadlja Donna , Ramić Alma , Zandona Antonio , Maraković Nikola , Brekalo Iva , Primožič Ines , Katalinić Maja
Published: December 2023

The cholinergic system, relying on the neurotransmitter acetylcholine (ACh), plays a significant role in muscle contraction, cognition, and autonomic nervous system regulation. The enzymes acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, responsible for hydrolyzing ACh, can fine-tune the cholinergic system’s activity and are, therefore, excellent pharmacological targets to address a range of medical conditions. We designed, synthesized, and profiled 14 N-alkyl quaternary quinuclidines as inhibitors of human AChE and BChE and analyzed their impact on cell viability to assess their safety in the context of application as potential therapeutics. Our results showed that all of the 14 tested quinuclidines inhibited both AChE and BChE in the micromolar range (Ki = 0.26 − 156.2 μM). The highest inhibition potency was observed for two bisquaternary derivatives, 7 (1,1′-(decano)bis(3-hydroxyquinuclidinium bromide)) and 14 (1,1′-(decano)bis(3-hydroxyiminoquinuclidinium bromide)). The cytotoxic effect within 7–200 μM was observed only for monoquaternary quinuclidine derivatives, especially those with the C12–C16 alkyl chain. Further analysis revealed a time-independent mechanism of action, significant LDH release, and a decrease in the cells’ mitochondrial membrane potential. Taking all results into consideration, we can confirm that a quinuclidine core presents a good scaffold for cholinesterase binding and that two bisquaternary quinuclidine derivatives could be considered as candidates worth further investigations as drugs acting in the cholinergic system. On the other hand, specific cell-related effects probably triggered by the free long alkyl chain in monoquaternary quinuclidine derivatives should not be neglected in future N-alkyl quaternary quinuclidine derivative structure refinements. Such an effect and their potential to interact with other specific targets, as indicated by a pharmacophore model, open up a new perspective for future investigations of these compounds’ scaffold in the treatment of specific conditions and diseases other than cholinergic system-linked disorders.
Metalloproteomic Investigation of Hg-Binding Proteins in Renal Tissue of Rats Exposed to Mercury Chloride
Authors: de Almeida Emerson Carlos , Faria Victor Diego , Cirinêu Felipe Dalmazzo , Santiago Maria G. A. , Miotto Beatriz , Vieira José C. S. , Braga Camila Pereira , Adamec Jiri , Fernandes Ana A. H. , Buzalaf Marília A. R. , Padilha Pedro de Magalhães
Published: December 2023

Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg−1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 “upregulated” proteins (p > 0.95) and 47 “downregulated” proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg−1, which qualifies these proteins as potential mercury-exposure biomarkers.
Offensive Text Span Detection in Romanian Comments Using Large Language Models
Authors: Paraschiv Andrei , Ion Teodora Andreea , Dascalu Mihai
Published: December 2023

The advent of online platforms and services has revolutionized communication, enabling users to share opinions and ideas seamlessly. However, this convenience has also brought about a surge in offensive and harmful language across various communication mediums. In response, social platforms have turned to automated methods to identify offensive content. A critical research question emerges when investigating the role of specific text spans within comments in conveying offensive characteristics. This paper conducted a comprehensive investigation into detecting offensive text spans in Romanian language comments using Transformer encoders and Large Language Models (LLMs). We introduced an extensive dataset of 4800 Romanian comments annotated with offensive text spans. Moreover, we explored the impact of varying model sizes, architectures, and training data volumes on the performance of offensive text span detection, providing valuable insights for determining the optimal configuration. The results argue for the effectiveness of BERT pre-trained models for this span-detection task, showcasing their superior performance. We further investigated the impact of different sample-retrieval strategies for few-shot learning using LLMs based on vector text representations. The analysis highlights important insights and trade-offs in leveraging LLMs for offensive-language-detection tasks.
Bactericera tremblayi (Wagner, 1961) (Hemiptera: Triozidae): The Prevalent Psyllid Species in Leek Fields of Northwestern Spain
Authors: Santiago-Calvo Yolanda , Baños-Picón Laura , Flores-Pérez Diego , Asensio-S.-Manzanera M.
Published: December 2023

Bactericera tremblayi (Wagner, 1961) (Hemiptera: Triozidae), the onion and leek psyllid, belongs to the Bactericera nigricornis Förster complex, along with B. trigonica and B. nigricornis. In contrast to the other two species, there has been a notable absence of studies examining the distribution and seasonal occurrence of B. tremblayi, despite its association with significant issues in leek crops. Surveys were conducted between 2017 and 2020 in the main leek-growing area of Castile and Leon (Spain). An extensive survey encompassing 29 distinct plots was monitored with sweep nets and visual inspection, counting plants with immature forms at three times in the crop cycle. Additionally, a total of seven seasonal monitoring surveys were conducted in the same area of study. Plots were monitored every ten days, employing three distinct sampling methods including horizontal green tile water traps, sweep nets, and visual inspection, counting the juvenile stages by plant. The results revealed that B. tremblayi predominated as the primary species of jumping plant-lice in leek crops throughout the entire crop cycle. To date, there exists no documented incidence of pathogenic agents within symptomatic leeks. Consequently, the manifestation of severe symptoms is highly likely to be a direct consequence of the feeding activity of the onion psyllid. Populations of B. tremblayi were present in leek crops from May–July to harvest (September–November). Adults were captured in horizontal green water traps several days before they were found in sweep net samples, making the former effective in capturing early immigrant individuals. The maximum peaks of B. tremblayi were observed at the end of the crop cycle, particularly during late-season cycles characterized by lower mean temperatures. During observations made in a controlled environment, temperature exerted a significant influence on the developmental time of all stages of B. tremblayi. The complete development from egg to adult occurred within a temperature range of 15 to 25 °C. At 30 °C, the survival of eggs and N1 nymphs was limited and B. tremblayi did not complete its developmental cycle. The optimum temperature for the development of B. tremblayi provided by the models used was close to 24 °C with the application of Briere, Taylor, and Lactin models and around 21 °C with the SSI model. These results provided a good adjustment in predicting the survival patterns of B. tremblayi under the studied environmental conditions.
Winter Rains Support Butterfly Diversity, but Summer Monsoon Rainfall Drives Post-Monsoon Butterfly Abundance in the Arid Southwest of the US
Authors: Rowe Helen Ivy , Johnson Bradly , Broatch Jennifer , Cruz Terese Maxine Papag , Prudic Kathleen L.
Published: December 2023

Butterfly populations are declining worldwide, reflecting our current global biodiversity crisis. Because butterflies are a popular and accurate indicator of insect populations, these declines reflect an even more widespread threat to insects and the food webs upon which they rely. As small ectotherms, insects have a narrow range of habitable conditions; hence, extreme fluctuations and shifts caused by climate change may increase insects’ risk of extinction. We evaluated trends of butterfly richness and abundance and their relationship with relevant climate variables in Arizona, U.S.A., using the past 40 years of community science data. We focused on precipitation and temperature as they are known to be influential for insect survival, particularly in arid areas like southwestern U.S.A. We found that preceding winter precipitation is a driver of both spring and summer/fall butterfly richness and spring butterfly abundance. In contrast, summer/fall butterfly abundance was driven by summer monsoon precipitations. The statistically significant declines over the 40-year period were summer/fall butterfly abundance and spring butterfly richness. When controlling for the other variables in the model, there was an average annual 1.81% decline in summer/fall season butterfly abundance and an average annual decline of 2.13 species in the spring season. As climate change continues to negatively impact winter precipitation patterns in this arid region, we anticipate the loss of butterfly species in this region and must consider individual butterfly species trends and additional management and conservation needs.
Advancements in Basal Cell Carcinoma Diagnosis: Non-Invasive Imaging and Multimodal Approach
Authors: Negrutiu Mircea , Danescu Sorina , Popa Theodor , Focșan Monica , Vesa Ștefan Cristian , Baican Adrian
Published: December 2023

(1) Background: The aim of this study was to correlate the diagnostic criteria described in dermatoscopy, ultrasonography (US), ex vivo confocal microscopy, and histology to the most common subtypes of basal cell carcinoma (BCC). (2) Methods: We conducted a prospective study including 46 BCC cases, which were analyzed with dermatoscopy using the Delta 30 dermatoscope and Vidix 4.0 videodermoscope, with US using a high-resolution 20 MHz linear probe, with confocal microscopy, along with histopathological analysis. (3) Results: This study categorized BCC by histological subtype, with nodular being the most common (84.8%) and various other subtypes represented. US measurements of tumor thickness correlated strongly with the histopathological depth of invasion index (DI). Dermatoscopy analysis revealed significant associations between specific features and BCC subtypes. The DI was directly related to arborized vessels but inversely related to short, fine telangiectasias, maple-leaf-like areas, and spoke-wheel areas. The presence of ulceration was directly related to the DI. Confocal microscopy images exhibited several characteristics, including fluorescence, nuclear crowding, peripheral palisading, clefting, increased nuclear–cytoplasmic (N/C) ratio, and a “cauliflower-like” appearance. (4) Conclusion: The advanced detection of BCC through imagistic techniques like dermatoscopy, confocal microscopy, and ultrasound improves the diagnosis and may offer valuable insights for treatment in the future by evaluating lesion characteristics.
Conservative Management in End-Stage Kidney Disease between the Dialysis Myth and Neglected Evidence-Based Medicine
Authors: Martino Francesca K. , Novara Giacomo , Nalesso Federico , Calò Lorenzo A.
Published: December 2023

In the last few decades, the aging of the general population has significantly increased the number of elderly patients with end-stage kidney disease (ESKD) who require renal replacement therapy. ESKD elders are often frail and highly comorbid with social issues and seem to not benefit from dialysis in terms of survival and quality of life. Conservative management (CM) could represent a valid treatment option, allowing them to live for months to years with a modest impact on their habits. Despite these possible advantages, CM remains underused due to the myth of dialysis as the only effective treatment option for all ESKD patients regardless of its impact on quality of life and survival. Both CM and dialysis remain valid alternatives in the management of ESKD. However, assessing comorbidities, disabilities, and social context should drive the choice of the best possible treatment for ESKD, while in elderly patients with short life expectancies, referring them to palliative care seems the most reasonable choice.
Determination of Peak Oxygen Uptake in Patients with Acute Myocardial Infarction: The Role of Arterial Stiffness in Cardio–Vascular–Skeletal Muscle Coupling
Authors: Ogawa Akihiro , Kanzaki Shinya , Ikeda Yuki , Iwakawa Masahiro , Nakagami Takahiro , Sato Shuji , Mikamo Hiroshi , Kido Satoshi , Nakajima Arata , Shimizu Kazuhiro
Published: December 2023

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardio–skeletal muscle coupling during exercise was then elucidated. Upon discharge, we measured exercise capacity using cardiopulmonary exercise testing (CPX), assessed arterial stiffness with the cardio–ankle vascular index (CAVI), and determined body composition to assess the skeletal muscle mass of 101 patients with AMI. Patients were categorized based on their CAVI scores into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and VO2 Peak during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply causes systemic exercise limits in patients with AMI. This suggests that arterial stiffness plays a significant role in cardio–vascular–skeletal muscle coupling.