bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Application of Droplet Digital PCR Assay for the Detection of Watermelon Silver Mottle Virus and Melon Yellow Spot Virus
Authors: Wu Huijie , Liu Mei , Li Wenyang , Wang Min , Xiu Junqing , Peng Bin , Hu Yanping , Kang Baoshan , Liu Liming , Gu Qinsheng
Published: February 2024

Watermelon silver mottle virus (WSMoV) and melon yellow spot virus (MYSV) (Tospoviridae, Orthotospovirus) are responsible for silver mottle mosaic and yellow spot symptoms, posing threats to melon (Cucumis melo), watermelon (Citrullus lanatus), and cucumber and leading to significant economic losses in China. Early disease detection and monitoring of these two viruses are necessary for disease management, for which a rapid, reliable, and adaptable diagnostic method is required. In this study, using a droplet digital PCR (ddPCR) method, the conserved region of the nucleocapsid gene (N gene) sequence was detected in WSMoV and MYSV. The probes and primers for WSMoV and MYSV did not detect other relevant cucurbit viruses, and the specificity reached 100%. Although both qPCR and ddPCR exhibited good reproducibility, the reproducibility of ddPCR was better than that of qPCR. The reproducibility of ddPCR was proved to be 100%. Moreover, ddPCR exhibited a good linear correlation with varying concentrations of targets. The detection limits of WSMoV and MYSV in ddPCR were 18 and 9 copies/μL and were approximately 12- and 18-times more than those in qPCR, respectively. Finally, 62 samples collected from the field (including infected melon, watermelon, and weeds) were further evaluated for the presence of WSMoV and MYSV. The field samples exhibited 91.94% and 51.61% positivity rates in ddPCR assays for WSMoV and MYSV, respectively; the rates were higher than those in qPCR (59.68% and 43.39%, respectively). The results indicated that ddPCR has a higher accuracy than qPCR. Therefore, ddPCR could be used in the clinical diagnosis of early infections of WSMoV and MYSV. To the best of our knowledge, this is the first study to establish a ddPCR method for the detection of WSMoV and MYSV. The application of this method for differential detection of MYSV and WSMoV will help in understanding the epidemics caused by these two important viruses and provide important information for the early detection, monitoring, and rapid extermination of infection.
Reconstruction of 3D Information of Buildings from Single-View Images Based on Shadow Information
Authors: Li Zhixin , Ji Song , Fan Dazhao , Yan Zhen , Wang Fengyi , Wang Ren
Published: February 2024

Accurate building geometry information is crucial for urban planning in constrained spaces, fueling the growing demand for large-scale, high-precision 3D city modeling. Traditional methods like oblique photogrammetry and LiDAR prove time consuming and expensive for low-cost 3D reconstruction of expansive urban scenes. Addressing this challenge, our study proposes a novel approach to leveraging single-view remote sensing images. By integrating shadow information with deep learning networks, our method measures building height and employs a semantic segmentation technique for single-image high-rise building reconstruction. In addition, we have designed complex shadow measurement algorithms and building contour correction algorithms to improve the accuracy of building models in conjunction with our previous research. We evaluate the method’s precision, time efficiency, and applicability across various data sources, scenarios, and scales. The results demonstrate the rapid and accurate acquisition of 3D building data with maintained geometric accuracy (mean error below 5 m). This approach offers an economical and effective solution for large-scale urban modeling, bridging the gap in cost-efficient 3D reconstruction techniques.
Solanum lycopersicum (Tomato)-Derived Nanovesicles Accelerate Wound Healing by Eliciting the Migration of Keratinocytes and Fibroblasts
Authors: Daniello Valeria , De Leo Vincenzo , Lasalvia Maria , Hossain Md Niamat , Carbone Annalucia , Catucci Lucia , Zefferino Roberto , Ingrosso Chiara , Conese Massimo , Di Gioia Sante
Published: February 2024

Plant-derived nanovesicles have been considered interesting in medicine for their breakthrough biological effects, including those relevant to wound healing. However, tomato-derived nanovesicles (TDNVs) have not been studied for their effects on wound closure yet. TDNVs were isolated from Solanum lycopersicum (var. Piccadilly) ripe tomatoes by ultracentrifugation. Extract (collected during the isolation procedure) and NVs (pellet) were characterized by transmission electron microscopy and laser Doppler electrophoresis. Wound healing in the presence of Extract or NVs was analyzed by a scratch assay with monocultures of human keratinocytes (HUKE) or NIH-3T3 mouse fibroblasts. Cell proliferation and migration were studied by MTT and agarose spot assay, respectively. The vesicles in the Extract and NV samples were nanosized with a similar mean diameter of 115 nm and 130 nm, respectively. Both Extract and NVs had already accelerated wound closure of injured HUKE and NIH-3T3 monocultures by 6 h post-injury. Although neither sample exerted a cytotoxic effect on HUKE and NIH-3T3 fibroblasts, they did not augment cell proliferation. NVs and the Extract increased cell migration of both cell types. NVs from tomatoes may accelerate wound healing by increasing keratinocyte and fibroblast migration. These results indicate the potential therapeutic usefulness of TDNVs in the treatment of chronic or hard-to-heal ulcers.
Glycyrol Alleviates Acute Kidney Injury by Inhibiting Ferroptsis
Authors: Cao Lixing , Han Kai , Fan Lihong , Zhao Chong , Yin Shutao , Hu Hongbo
Published: February 2024

Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.
Changes in the Expression of Proteins Associated with Neurodegeneration in the Brains of Mice after Infection with Influenza A Virus with Wild Type and Truncated NS1
Authors: Donátová Karin , Mladá Miriam , Lopušná Katarína , Baran Filip , Betáková Tatiana
Published: February 2024

Influenza type A virus (IAV) infection is a major cause of morbidity and mortality during influenza epidemics. Recently, a specific link between IAV infection and neurodegenerative disease progression has been established. The non-structural NS1 protein of IAV regulates viral replication during infection and antagonizes host antiviral responses, contributing to influenza virulence. In the present study, we have prepared a mouse lung-to-lung adapted to the NS1-truncated virus (NS80ad). Transcriptome analysis of the gene expression in the lungs revealed that infection with wild-type A/WSN/33 (WSN), NS80, and NS80ad viruses resulted in different regulation of genes involved in signaling pathways associated with the cell proliferation, inflammatory response, and development of neurodegenerative diseases. NS1 protein did not influence the genes involved in the RIG-I-like receptor signaling pathway in the brains. Lethal infection with IAVs dysregulated expression of proteins associated with the development of neurodegenerative diseases (CX3CL1/Fractalkine, Coagulation factor III, and CD105/Endoglin, CD54/ICAM-1, insulin-like growth factor-binding protein (IGFBP)-2, IGFBP-5, IGFBP-6, chitinase 3-like 1 (CHI3L1), Myeloperoxidase (MPO), Osteopontin (OPN), cystatin C, and LDL R). Transcription of GATA3 mRNA was decreased, and expression of MPO was inhibited in the brain infected with NS80 and NS80ad viruses. In addition, the truncation of NS1 protein led to reduced expression of IGFBP-2, CHI3L1, MPO, and LDL-R proteins in the brains. Our results indicate that the influenza virus influences the expression of proteins involved in brain function, and this might occur mostly through the NS1 protein. These findings suggest that the abovementioned proteins represent a promising target for the development of potentially effective immunotherapy against neurodegeneration.
Use of microRNAs as Diagnostic, Prognostic, and Therapeutic Tools for Glioblastoma
Authors: Valle-Garcia David , Pérez de la Cruz Verónica , Flores Itamar , Salazar Aleli , Pineda Benjamín , Meza-Sosa Karla
Published: February 2024

Glioblastoma (GB) is the most aggressive and common type of cancer within the central nervous system (CNS). Despite the vast knowledge of its physiopathology and histology, its etiology at the molecular level has not been completely understood. Thus, attaining a cure has not been possible yet and it remains one of the deadliest types of cancer. Usually, GB is diagnosed when some symptoms have already been presented by the patient. This diagnosis is commonly based on a physical exam and imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), together with or followed by a surgical biopsy. As these diagnostic procedures are very invasive and often result only in the confirmation of GB presence, it is necessary to develop less invasive diagnostic and prognostic tools that lead to earlier treatment to increase GB patients’ quality of life. Therefore, blood-based biomarkers (BBBs) represent excellent candidates in this context. microRNAs (miRNAs) are small, non-coding RNAs that have been demonstrated to be very stable in almost all body fluids, including saliva, serum, plasma, urine, cerebrospinal fluid (CFS), semen, and breast milk. In addition, serum-circulating and exosome-contained miRNAs have been successfully used to better classify subtypes of cancer at the molecular level and make better choices regarding the best treatment for specific cases. Moreover, as miRNAs regulate multiple target genes and can also act as tumor suppressors and oncogenes, they are involved in the appearance, progression, and even chemoresistance of most tumors. Thus, in this review, we discuss how dysregulated miRNAs in GB can be used as early diagnosis and prognosis biomarkers as well as molecular markers to subclassify GB cases and provide more personalized treatments, which may have a better response against GB. In addition, we discuss the therapeutic potential of miRNAs, the current challenges to their clinical application, and future directions in the field.
Synergistic Anti-Cancer Effects of ERB-041 and Genistein through Estrogen Receptor Suppression-Mediated PI3K/AKT Pathway Downregulation in Canine Mammary Gland Tumor Cells
Authors: Yoo Min-Jae , Jang Ye-Ji , Park Sang-Youel , Choi Ja-Wun , Seol Jae-Won
Published: February 2024

Canine-mammary-gland tumors (CMTs) are prevalent in female dogs, with approximately 50% of them being malignant and often presenting as inoperable owing to their size or metastasis. Owing to poor outcomes, effective alternatives to conventional chemotherapy for humans are necessary. Two estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), which act in opposition to each other, are involved, and CMT growth involves ERα through the phosphoinositide 3-kinases (PI3K)/AKT pathway. In this study, we aimed to identify the synergistic anti-cancer effects of ERB-041, an ERβ agonist, and genistein, an isoflavonoid from soybeans known to have ERβ-specific pseudo-estrogenic actions, on CMT-U27 and CF41.Mg CMT cell lines. ERB-041 and genistein synergistically inhibited cell proliferation and increased the number of annexin V-positive cells in both cell lines. Furthermore, we observed a synergistic increase in the Bax/Bcl-2 ratio and cleaved caspase-3 expression. Additionally, cell-cycle arrest occurred through the synergistic regulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). We also found a synergistic decrease in the expression of ERα, and the expression of proteins involved in the PI3K/AKT pathway, including p-PI3K, phosphatase and tensin homolog (PTEN), AKT, and mechanistic target of rapamycin (mTOR). In conclusion, ERB-041 and genistein exhibited a synergistic anticancer effect on CMTs, suggesting that cotreatment with ERB-041 and genistein is a promising treatment for CMTs.
Arrhythmogenic Right Ventricular Cardiomyopathy Post-Mortem Assessment: A Systematic Review
Authors: Cianci Vincenzo , Forzese Elena , Sapienza Daniela , Cianci Alessio , Ieni Antonio , Germanà Antonino , Guerrera Maria Cristina , Omero Fausto , Speranza Desirèe , Cracò Annalisa , Asmundo Alessio , Gualniera Patrizia , Mondello Cristina
Published: February 2024

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased’s family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease.
Knockdown of DNMT1 Induces SLCO3A1 to Promote Follicular Growth by Enhancing the Proliferation of Granulosa Cells in Mammals
Authors: Li Shuo , Zeng Liqing , Miao Fen , Li Nian , Liao Weili , Zhou Xiaofeng , Chen Yongcai , Quan Hongyan , He Yingting , Zhang Hao , Li Jiaqi , Yuan Xiaolong
Published: February 2024

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) have been shown to determine the fate of follicles. DNA methyltransferases (DNMTs) and SLCO3A1 have been reported to be involved in the survival of GCs and follicular growth. However, the molecular mechanisms enabling DNMTs to regulate the expression of SLCO3A1 to participate in follicular growth are unclear. In this study, we found that the knockdown of DNMT1 enhanced the mRNA and protein levels of SLCO3A1 by regulating the chromatin accessibility probably. Moreover, SLCO3A1 upregulated the mRNA and protein levels of MCL1, PCNA, and STAR to promote the proliferation of GCs and facilitated cell cycle progression by increasing the mRNA and protein levels of CCNE1, CDK2, and CCND1, but it decreased apoptosis by downregulating the mRNA and protein levels of CASP3 and CASP8. Moreover, SLCO3A1 promoted the growth of porcine follicles and development of mice follicles. In conclusion, the knockdown of DNMT1 upregulated the mRNA and protein levels of SLCO3A1, thereby promoting the proliferation of GCs to facilitate the growth and development of ovarian follicles, and these results provide new insights into investigations of female reproductive diseases.
Endotoxin Inflammatory Action on Cells by Dysregulated-Immunological-Barrier-Linked ROS-Apoptosis Mechanisms in Gut–Liver Axis
Authors: Dumitru Andrei , Matei Elena , Cozaru Georgeta Camelia , Chisoi Anca , Alexandrescu Luana , Popescu Răzvan Cătălin , Butcaru Mihaela Pundiche , Dumitru Eugen , Rugină Sorin , Tocia Cristina
Published: February 2024

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut–liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut–liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields.
Molecular-Scale Investigations Reveal the Effect of Natural Polyphenols on BAX/Bcl-2 Interactions
Authors: Sun Heng , Liao Fenghui , Tian Yichen , Lei Yongrong , Fu Yuna , Wang Jianhua
Published: February 2024

Apoptosis signaling controls the cell cycle through the protein–protein interactions (PPIs) of its major B-cell lymphoma 2-associated x protein (BAX) and B-cell lymphoma 2 protein (Bcl-2). Due to the antagonistic function of both proteins, apoptosis depends on a properly tuned balance of the kinetics of BAX and Bcl-2 activities. The utilization of natural polyphenols to regulate the binding process of PPIs is feasible. However, the mechanism of this modulation has not been studied in detail. Here, we utilized atomic force microscopy (AFM) to evaluate the effects of polyphenols (kaempferol, quercetin, dihydromyricetin, baicalin, curcumin, rutin, epigallocatechin gallate, and gossypol) on the BAX/Bcl-2 binding mechanism. We demonstrated at the molecular scale that polyphenols quantitatively affect the interaction forces, kinetics, thermodynamics, and structural properties of BAX/Bcl-2 complex formation. We observed that rutin, epigallocatechin gallate, and baicalin reduced the binding affinity of BAX/Bcl-2 by an order of magnitude. Combined with surface free energy and molecular docking, the results revealed that polyphenols are driven by multiple forces that affect the orientation freedom of PPIs, with hydrogen bonding, hydrophobic interactions, and van der Waals forces being the major contributors. Overall, our work provides valuable insights into how molecules tune PPIs to modulate their function.
Immunological Landscapes in Lung Transplantation: Insights from T Cell Profiling in BAL and PBMC
Authors: de Silva Tharushi Ayanthika , Apte Simon , Voisey Joanne , Spann Kirsten , Tan Maxine , Chambers Daniel , O’Sullivan Brendan
Published: February 2024

Lung transplant recipients frequently encounter immune-related complications, including chronic lung allograft dysfunction (CLAD). Monitoring immune cells within the lung microenvironment is pivotal for optimizing post-transplant outcomes. This study examined the proportion of T cell subsets in paired bronchoalveolar lavage (BAL) and peripheral PBMC comparing healthy (n = 4) and lung transplantation patients (n = 6, no CLAD and n = 14 CLAD) using 14-color flow cytometry. CD4+ T cell proportions were reduced in CD3 cells in both PBMC and BAL, and positive correlations were discerned between T cell populations in peripheral PBMC and BAL, suggesting the prospect of employing less invasive PBMC sampling as a means of monitoring lung T cells. Furthermore, regulatory T cells (Tregs) were enriched in BAL when compared to peripheral PBMC for transplant recipients. A parallel positive correlation emerged between Treg proportions in BAL and peripheral PBMC, underscoring potential avenues for monitoring lung Tregs. Finally, the most promising biomarker was the Teff (CD8+Granzyme B+)–Treg ratio, which was higher in both the PBMC and BAL of transplant recipients compared to healthy individuals, and increased in the patients with CLAD compared to no CLAD and healthy patients. Conclusions: Distinct T cell profiles in BAL and peripheral PBMC underscore the significance of localized immune monitoring in lung transplantation. The Teff (CD8+granzyme B+)–Treg ratio, particularly within the context of CLAD, emerges as a promising blood and BAL biomarker reflective of inflammation and transplant-related complications. These findings emphasize the imperative need for personalized immune monitoring strategies that tailored to address the unique immunological milieu in post-transplant lungs.
Diffusion Mediates Molecular Transport through the Perivascular Space in the Brain
Authors: Tanaka Marie , Hirayoshi Yoko , Minatani Shinobu , Hasegawa Itsuki , Itoh Yoshiaki
Published: February 2024

The perivascular space has been proposed as a clearance pathway for degradation products in the brain, including amyloid β, the accumulation of which may induce Alzheimer’s disease. Live images were acquired using a two-photon microscope through a closed cranial window in mice. In topical application experiments, the dynamics of FITC-dextran were evaluated from 30 to 150 min after the application and closure of the window. In continuous injection experiments, image acquisition began before the continuous injection of FITC-dextran. The transport of dextran molecules of different sizes was evaluated. In topical application experiments, circumferential accumulation around the penetrating arteries, veins, and capillaries was observed, even at the beginning of the observation period. No further increases were detected. In continuous injection experiments, a time-dependent increase in the fluorescence intensity was observed around the penetrating arteries and veins. Lower-molecular-weight dextran was transported more rapidly than higher-molecular-weight dextran, especially around the arteries. The largest dextran molecules were not transported significantly during the observation period. The size-dependent transport of dextran observed in the present study strongly suggests that diffusion is the main mechanism mediating substance transport in the perivascular space.
Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle
Authors: Delort Alexandre , Cottone Grazia , Malliavin Thérèse E. , Müller Martin Michael
Published: February 2024

The toxicity of botulinum multi-domain neurotoxins (BoNTs) arises from a sequence of molecular events, in which the translocation of the catalytic domain through the membrane of a neurotransmitter vesicle plays a key role. A recent structural study of the translocation domain of BoNTs suggests that the interaction with the membrane is driven by the transition of an α helical switch towards a β hairpin. Atomistic simulations in conjunction with the mesoscopic Twister model are used to investigate the consequences of this proposition for the toxin–membrane interaction. The conformational mobilities of the domain, as well as the effect of the membrane, implicitly examined by comparing water and water–ethanol solvents, lead to the conclusion that the transition of the switch modifies the internal dynamics and the effect of membrane hydrophobicity on the whole protein. The central two α helices, helix 1 and helix 2, forming two coiled-coil motifs, are analyzed using the Twister model, in which the initial deformation of the membrane by the protein is caused by the presence of local torques arising from asymmetric positions of hydrophobic residues. Different torque distributions are observed depending on the switch conformations and permit an origin for the mechanism opening the membrane to be proposed.
Plasma Lipidomic Profiling Using Mass Spectrometry for Multiple Sclerosis Diagnosis and Disease Activity Stratification (LipidMS)
Authors: Lattau Seyed Siyawasch Justus , Borsch Lisa-Marie , auf dem Brinke Kristina , Klose Christian , Vinhoven Liza , Nietert Manuel , Fitzner Dirk
Published: February 2024

This investigation explores the potential of plasma lipidomic signatures for aiding in the diagnosis of Multiple Sclerosis (MS) and evaluating the clinical course and disease activity of diseased patients. Plasma samples from 60 patients with MS (PwMS) were clinically stratified to either a relapsing-remitting (RRMS) or a chronic progressive MS course and 60 age-matched controls were analyzed using state-of-the-art direct infusion quantitative shotgun lipidomics. To account for potential confounders, data were filtered for age and BMI correlations. The statistical analysis employed supervised and unsupervised multivariate data analysis techniques, including a principal component analysis (PCA), a partial least squares discriminant analysis (oPLS-DA) and a random forest (RF). To determine whether the significant absolute differences in the lipid subspecies have a relevant effect on the overall composition of the respective lipid classes, we introduce a class composition visualization (CCV). We identified 670 lipids across 16 classes. PwMS showed a significant increase in diacylglycerols (DAG), with DAG 16:0;0_18:1;0 being proven to be the lipid with the highest predictive ability for MS as determined by RF. The alterations in the phosphatidylethanolamines (PE) were mainly linked to RRMS while the alterations in the ether-bound PEs (PE O-) were found in chronic progressive MS. The amount of CE species was reduced in the CPMS cohort whereas TAG species were reduced in the RRMS patients, both lipid classes being relevant in lipid storage. Combining the above mentioned data analyses, distinct lipidomic signatures were isolated and shown to be correlated with clinical phenotypes. Our study suggests that specific plasma lipid profiles are not merely associated with the diagnosis of MS but instead point toward distinct clinical features in the individual patient paving the way for personalized therapy and an enhanced understanding of MS pathology.
Special Issue of Pathogenesis of Pregnancy-Related Complications, 2023
Authors: Hromadnikova Ilona
Published: February 2024

This Special Issue mainly focuses on preeclampsia (PE), haemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, gestational diabetes mellitus (GDM), foetal growth restriction (FGR), small-for-gestational-age foetuses (SGA), miscarriage, stillbirth, first-episode psychosis (FEP) during pregnancy, and pregnancy-related acute kidney injury (PR-AKI) [...]
Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients
Authors: Canino Fabio , Tornincasa Antonio , Bettelli Stefania , Manfredini Samantha , Barbolini Monica , Moscetti Luca , Omarini Claudia , Toss Angela , Tamburrano Fabio , Antonelli Giuseppina , Baglio Federica , Belluzzi Lorenzo , Martinelli Giulio , Natalizio Salvatore , Ponzoni Ornella , Dominici Massimo , Piacentini Federico
Published: February 2024

Over the last two decades, the use of Next-Generation Sequencing (NGS) in medical oncology has increased the likelihood of identifying druggable mutations that may be potentially susceptible to targeted treatments. The European Society for Medical Oncology (ESMO) currently does not recommend the use of the NGS test to determine the therapeutic course of patients with metastatic breast cancer (mBC) in daily clinical practice. However, the aim of this work is to evaluate the potential contribution of the NGS test in selecting targeted therapies for patients with mBC. Data were retrospectively collected from 101 patients diagnosed with metastatic breast cancer and treated at the Modena Cancer Center between January 2015 and April 2022. A NGS test was performed on the tumor tissue of each patient at the Laboratory of Molecular Pathology of the University Hospital of Modena. This study analyzed the clinical–pathological characteristics and mutational profile of the population using NGS tests, with a focus on actionable mutations that could be targeted in advanced stages of clinical development. The indicator of this study was to quantify the actionable mutations that resulted in a change of cancer treatment. In total, 101 patients with metastatic breast cancer were analyzed, including 86 with luminal phenotype, 10 who were HER2-positive and 5 who were triple-negative. Median age was 52 years. NGS analysis was conducted on 47 samples of primary breast cancer, 52 on metastatic sites of disease and 2 on liquid biopsies. A total of 85 gene mutations were found. The most common mutations were identified in the PIK3CA (47%), FGFR (19%) and ERBB2 genes (12%), and to a lesser extent in other genes. Of the 61 patients with pathogenic mutations, 46 (75%) had at least one actionable mutation. Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. Median PFS for these patients was 3.8 months. The study results show that using the NGS test on cancer tissue of metastatic breast cancer could influence the therapeutic choices, considering the small sample size and limited follow-up. About 9% of the study population had their therapy modified based on the results of NGS. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.
Vaginal Lactobacilli Supernatants Protect from Herpes Simplex Virus Type 1 Infection in Cell Culture Models
Authors: Avitabile Elisa , Menotti Laura , Giordani Barbara , Croatti Vanessa , Parolin Carola , Vitali Beatrice
Published: February 2024

A healthy vaginal microbiota hosts Lactobacillus as the most predominant genus. Lactobacilli play a role in human health through the production of diverse antimicrobial substances that can act against human pathogens or modulate the immune system. Previous reports highlighted the ability of vaginal lactobacilli to counteract viruses causing STIs, e.g., HIV-1 and HSV-2. In this report, we analyze the activity of supernatants of vaginal lactobacilli against HSV-1 infection, which is becoming increasingly relevant as a STI. We show that the supernatants of two vaginal Lactobacillus species (i.e., L. crispatus and L. gasseri) were active at neutralizing HSV-1 infection in two different cell lines of human and simian origin. Specifically, we demonstrate that L. crispatus strains are the most effective in antiviral activity, as evidenced by the comparison with a vaginal pathogen taken as reference. The effect was specific and not attributable to the generic toxicity of the supernatants to the cells. Our results pave the way for the development of probiotics to limit the impact of HSV-1 infection on women’s health.
The Effect of Sleep Quality on Coronary Lesion Severity and Prognosis in the Young Acute Coronary Syndrome Population
Authors: Yang Jiaxin , Wang Kexin , Wang Wenjie , Niu Jialong , Liu Xiaoli , Shen Hua , Sun Yan , Ge Hailong , Han Hongya
Published: February 2024

This study aimed to explore the effect of long-term (≥1 year) sleep quality on coronary lesion complexity and cardiovascular prognosis in young acute coronary syndrome (ACS) patients. We consecutively recruited young patients aged from 18 to 44 years old with first-episode ACS and significant epicardial stenosis on coronary angiography from January 2016 to January 2017. Coronary lesion complexity was evaluated based on SYNTAX scores. Long-term sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) (PSQI ≤ 5 and PSQI > 5 groups). The primary endpoints were major adverse cardiovascular events (MACEs). A total of 466 young ACS patients (93.13% male; median age, 41 years) were included. Poor sleepers (PSQI > 5) had higher SYNTAX scores. After adjusting for confounders, PSQI scores (continuous variables, OR: 1.264; 95%CI: 1.166–1.371; p < 0.001) and PSQI grade (binary variable, OR: 3.864; 95%CI: 2.313–6.394; p = 0.001) were significantly associated with an increased risk of complex coronary lesions. During a median follow-up of 74 months, long-term poor sleep quality (PSQI > 5) was significantly associated with an increased risk of MACEs (HR: 4.266; 95%CI: 2.274–8.001; p < 0.001). Long-term poor sleep quality was a risk factor for complex coronary lesions and has adverse effects on cardiovascular prognosis in the young ACS population.
Early Feasibility Study of a Hybrid Tissue-Engineered Mitral Valve in an Ovine Model
Authors: Zareian Ramin , Zuke Samuel D. , Morisawa Daisuke , Geertsema Roger S. , Majid Mariwan , Wynne Clinton , Milliken Jeffrey C. , Kheradvar Arash
Published: February 2024

Tissue engineering aims to overcome the current limitations of heart valves by providing a viable alternative using living tissue. Nevertheless, the valves constructed from either decellularized xenogeneic or purely biologic scaffolds are unable to withstand the hemodynamic loads, particularly in the left ventricle. To address this, we have been developing a hybrid tissue-engineered heart valve (H-TEHV) concept consisting of a nondegradable elastomeric scaffold enclosed in a valve-like living tissue constructed from autologous cells. We developed a 21 mm mitral valve scaffold for implantation in an ovine model. Smooth muscle cells/fibroblasts and endothelial cells were extracted, isolated, and expanded from the animal’s jugular vein. Next, the scaffold underwent a sequential coating with the sorted cells mixed with collagen type I. The resulting H-TEHV was then implanted into the mitral position of the same sheep through open-heart surgery. Echocardiography scans following the procedure revealed an acceptable valve performance, with no signs of regurgitation. The valve orifice area, measured by planimetry, was 2.9 cm2, the ejection fraction reached 67%, and the mean transmitral pressure gradient was measured at 8.39 mmHg. The animal successfully recovered from anesthesia and was transferred to the vivarium. Upon autopsy, the examination confirmed the integrity of the H-TEHV, with no evidence of tissue dehiscence. The preliminary results from the animal implantation suggest the feasibility of the H-TEHV.
Advanced Ti–Nb–Ta Alloys for Bone Implants with Improved Functionality
Authors: Sass Jan-Oliver , Sellin Marie-Luise , Kauertz Elisa , Johannsen Jan , Weinmann Markus , Stenzel Melanie , Frank Marcus , Vogel Danny , Bader Rainer , Jonitz-Heincke Anika
Published: February 2024

The additive manufacturing of titanium–niobium–tantalum alloys with nominal chemical compositions Ti–xNb–6Ta (x = 20, 27, 35) by means of laser beam powder bed fusion is reported, and their potential as implant materials is elaborated by mechanical and biological characterization. The properties of dense specimens manufactured in different build orientations and of open porous Ti–20Nb–6Ta specimens are evaluated. Compression tests indicate that strength and elasticity are influenced by the chemical composition and build orientation. The minimum elasticity is always observed in the 90° orientation. It is lowest for Ti–20Nb–6Ta (43.2 ± 2.7 GPa) and can be further reduced to 8.1 ± 1.0 GPa for open porous specimens (p < 0.001). Furthermore, human osteoblasts are cultivated for 7 and 14 days on as-printed specimens and their biological response is compared to that of Ti–6Al–4V. Build orientation and cultivation time significantly affect the gene expression profile of osteogenic differentiation markers. Incomplete cell spreading is observed in specimens manufactured in 0° build orientation, whereas widely stretched cells are observed in 90° build orientation, i.e., parallel to the build direction. Compared to Ti–6Al–4V, Ti–Nb–Ta specimens promote improved osteogenesis and reduce the induction of inflammation. Accordingly, Ti–xNb–6Ta alloys have favorable mechanical and biological properties with great potential for application in orthopedic implants.
Advanced Platelet Lysate Aerogels: Biomaterials for Regenerative Applications
Authors: Tibourtine Fahd , Canceill Thibault , Marfoglia Andrea , Lavalle Philippe , Gibot Laure , Pilloux Ludovic , Aubry Clementine , Medemblik Claire , Goudouneche Dominique , Dupret-Bories Agnès , Cazalbou Sophie
Published: February 2024

Human platelet lysate (HPL), rich in growth factors, is increasingly recognized for its potential in tissue engineering and regenerative medicine. However, its use in liquid or gel form is constrained by limited stability and handling difficulties. This study aimed to develop dry and porous aerogels from HPL hydrogel using an environmentally friendly supercritical CO2-based shaping process, specifically tailored for tissue engineering applications. The aerogels produced retained their three-dimensional structure and demonstrated significant mechanical robustness and enhanced manageability. Impressively, they exhibited high water absorption capacity, absorbing 87% of their weight in water within 120 min. Furthermore, the growth factors released by these aerogels showed a sustained and favourable biological response in vitro. They maintained the cellular metabolic activity of fibroblasts (BALB-3T3) at levels akin to conventional culture conditions, even after prolonged storage, and facilitated the migration of human umbilical vein endothelial cells (HUVECs). Additionally, the aerogels themselves supported the adhesion and proliferation of murine fibroblasts (BALB-3T3). Beyond serving as excellent matrices for cell culture, these aerogels function as efficient systems for the delivery of growth factors. Their multifunctional capabilities position them as promising candidates for various tissue regeneration strategies. Importantly, the developed aerogels can be stored conveniently and are considered ready to use, enhancing their practicality and applicability in regenerative medicine.
Structural Features and Phylogenetic Implications of Crinoid Echinoderms Based on Thirteen Novel Mitochondrial Genomes
Authors: Xu Qinzeng , Lu Min , Sun Yuyao , Li Zhong , Li Yixuan , Dong Yue , Hu Xuying , Zhang Qian , Liu Bing , He Xuebao
Published: February 2024

Crinoids, as integral echinoderms, play a crucial ecological role in benthic communities, serving as significant indicators reflecting the health of marine ecosystems. However, the phylogenetic relationships within crinoids are unclear. More molecular data can help to facilitate biodiversity assessment and elucidate evolutionary relationships by the phylogenetic tree. In this study, 13 complete mitochondrial genomes of the Crinoidea class were sequenced, annotated, and compared with other same class species available on NCBI. The results reveal five different gene order patterns among these mitochondrial genomes, indicating that crinoids have undergone gene rearrangements during evolution. The complete mitochondrial genome length of crinoids ranges from 15,772 bp to 16,850 bp. High A + T content, ranging from 64.5% to 74.2%, was observed. Additionally, our analysis of protein-coding genes highlights a preference for A + T nucleotides, along with specific start and stop codon usage, offering insights into codon bias and its implications for protein synthesis and function. The phylogenetic topology shows that the stalkless crinoid and stalked crinoid are distinct, and the phylogenetic trees generated based on maximum likelihood and Bayesian inference are almost identical at the family and order topology levels. The phylogenetic relationships of each family were fully clarified in four orders. A total of eleven positive selection sites were detected within six genes: cytb, nad2, nad3, nad4, nad4L and nad5. This study reveals the phylogenetic relationships of crinoid species, the mitochondrial gene differences, and the selective pressure on the evolution of stalked crinoids. This study significantly enhanced the crinoid mitochondrial genome database and contributed to a better understanding of the phylogenetic relationships among crinoid echinoderms.
Distributed Lyapunov-Based Model Predictive Control for AUV Formation Systems with Multiple Constraints
Authors: Yan Zheping , Zhang Mingyao , Zhou Jiajia , Yue Lidong
Published: February 2024

This paper focuses on the formation tracking issue of autonomous underwater vehicles (AUVs) subject to multiple constraints in three-dimensional space. We developed a novel distributed Lyapunov-based model predictive controller (DLMPC) with a fast finite-time extended state observer (FFTESO). Initially, the external disturbances and internal uncertainties of each AUV were precisely compensated using the designed FFTESO. Subsequently, we proposed DLMPC-based position tracking and velocity tracking controllers, which solved an online optimization problem to determine optimal velocities and control forces. This hierarchical framework effectively managed system constraints, such as state constraints and actuator saturation. Additionally, the Lyapunov-based backstepping control law was applied to construct stability constraints in the distributed optimization problem, ensuring the recursive feasibility and closed-loop system stability of the proposed scheme. Sufficient conditions and attraction regions to ensure stability were explicitly provided. Finally, the simulation results demonstrated that the proposed method improved both the convergence speed and tracking accuracy by at least 30% compared to other methods.
The Impact of Crime against a Person on Domestic Investment in Dubai
Authors: Adela Hatem , Aldhaheri Wadeema
Published: February 2024

The rise in crime against a person in rapidly growing cities poses significant risks to societies and economies, affecting both microeconomic and macroeconomic aspects. This trend could potentially deter economic performance and domestic investment. Consequently, this study aims to analyze the impact of crime against a person on domestic investment in Dubai spanning 1989–2021. Dubai is considered an emerging economy and a highly competitive global city. It is also acknowledged as one of the world’s smart cities. This study employed the novel nonlinear autoregressive distributed lag (NARDL) approach to investigate the impact of both the escalation and contraction of crime against a person on domestic investment in Dubai. The findings exhibit that the fluctuation in crime against a person has an asymmetrical impact on domestic investment. In addition, estimations of the positive and negative long-run asymmetric coefficients indicate that crime against a person has a negative impact on domestic investment in Dubai.
How Consideration of Future Consequences, Prior Gain or Loss, Personal Risk Profile, and Justification Affect Risk–Payoff Preferences
Authors: Lee W. Eric
Published: February 2024

This study examines (1) how risk–payoff preference can be affected by differences in consideration of future consequences (CFC), prior gain/loss, and personal risk profile, and (2) whether one’s risk–payoff preference may vary with justification prompts. Using an experimental design with 366 undergraduate business students, participants are tasked to make risk–payoff choices in two scenarios, with the combined risk–payoff outcomes serving as the dependent variable. In addition, participants are assessed on their personal risk profiles and also complete the 14-item CFC scale to gauge the propensity to take into account future consequences of their behaviors. Findings show that one who scores low (high) in CFC will prefer lower (higher) risk and payoff. Further, for an individual who scores high in CFC and has a prior gain (loss), he/she will be more inclined to prefer lower (higher) risk and payoff, though this effect is moderated by one’s risk profile. Finally, justification prompts help to reduce one’s propensity toward high risk–payoff, irrespective of prior gain/loss and risk profile considerations. With regard to consumers’ financial choices, particularly in a volatile economic environment, the findings here indicate that prompting for strategic justifications before making decisions can help lower one’s overall propensity toward high risk–payoff choices.
Prevalence of Obesity and Associated Dietary Habits among Medical Students at King Khalid University, Southwestern Saudi Arabia
Authors: Mahfouz Ahmed A. , Alsaleem Safar Abadi , Alsaleem Mohammed Abadi , Ghazy Ramy Mohamed
Published: February 2024

Background and Objectives: Healthy eating is a crucial approach to improving overall health, encompassing a well-balanced diet of natural and fresh foods, plenty of fruits and vegetables, and foods rich in minerals and vitamins. This study aimed to assess the prevalence of obesity and associated dietary habits among medical students at King Khalid University, Aseer, Saudi Arabia. Materials and Methods: This observational cross-sectional study was conducted through face-to-face interviews. A structured predesigned questionnaire was used to collect data. Results: A total of 540 medical students were included; 43.3% of participants were aged 20–22 years, 24.8% were in the 3rd year, and 82.0% had an average income level. Of them, 21.9% were overweight and 14.6% were obese. There was a significant association between obesity and grade (p = 0.004). Significant differences were observed between males and females in adding sugar to beverages, the frequency of eating out, cooking meat, and drinking water (p < 0.05). The predictors of obesity were being male (OR = 3.5, 95% CI [1.6–7.8], p = 0.002), age (OR = 1.8, 95% CI [1.1–3.0, p = 0.019], being at grade 2 (OR = 38.8, 95% CI [4.0–375.8], p = 0.002), having grilled meat (OR = 0.42, 95% CI, [0.20–0.99], p = 0.048), using artificial sweeteners [OR = 0.24, 95% CI [0.08–0.73], p = 0.012], and drinking sparkling bottled water (OR 8.6, 95% CI [1.2 333–63.8], p = 0.034). Conclusions: The study revealed a high prevalence of obesity and overweight among medical students of both sexes. It recommends education on healthy eating habits, balanced nutrition, and regular physical activity, as well as gender-specific health initiatives, nutritional counseling, and the inclusion of physical activity.