bluuebunny/crossref_metadata_2025 huggingface dataset:
Child Welfare Investigations of Exposure to Intimate Partner Violence Referred by Medical Professionals in Ontario: A Uniquely Vulnerable Population?
Authors: Joh-Carnella Nicolette , Livingston Eliza , Stoddart Jill , Fallon Barbara
Published: September 2023

Victims of intimate partner violence (IPV) and their children may be at an increased risk for negative health outcomes and may present to healthcare settings. The objective of the current study is to examine the profile of medical-referred child welfare investigations of exposure to IPV in Ontario, Canada. Data from the Ontario Incidence Study of Reported Child Abuse and Neglect 2018 were used. We compared medical-referred investigations with all other investigations of exposure to IPV. Descriptive and bivariate analyses as well as a logistic regression predicting transfers to ongoing services were conducted. Six percent of investigations of exposure to IPV conducted in Ontario in 2018 were referred by a medical source. Compared to other investigations of exposure to IPV, these investigations were more likely to involve younger children (p = 0.005), caregivers with mental health issues (p < 0.001) and few social supports (p = 0.004), and households noted to be overcrowded (p = 0.001). After controlling for clinical case characteristics, investigations of exposure to IPV referred by healthcare sources were 3.452 times as likely to be kept open for ongoing child welfare services compared to those referred by other sources (95% CI [2.024, 5.886]; p < 0.001). Children and their families who are identified in healthcare settings for concerns of exposure to IPV tend to receive extended child welfare intervention compared to those identified elsewhere. There is a clear difference in service provision in healthcare-originating investigations of exposure to IPV versus investigations originating from other sources. Further research into the services provided to victims of IPV and their children is needed.
Grafting Compatibility and Environmental Conditions on Soilless Eggplant (Solanum melongena) Grown in the Mediterranean Greenhouse
Authors: Argento Sergio , Treccarichi Simone , Melilli Maria Grazia , Branca Ferdinando
Published: September 2023

Grafting techniques represent an efficient tool to enhance plant growth and development. The study aims to explore the effects of different grafting combinations on the growth of eggplants under diverse greenhouse conditions. Eggplant cultivar Black bell (Bb) was employed as scion, while the hybrid F1 Beaufort (Be) and Solanum torvum (To) were utilized as rootstock. The hypothesis behind this study pertains to grafting incompatibility with Beaufort F1. It postulates that this incompatibility can be mitigated by manipulating soil and greenhouse temperatures. The experimental factors encompassed plant combinations (Bb, Be/Bb and To/Bb), as well greenhouse and substrate temperature (both cold or heated). The Be/Bb combination showed higher values of plant vegetative traits, but it exhibited low grafting compatibility. Additionally, physiological analysis confirmed the presence of excessive growth and vegetative disorder within the Be/Bb combination. Examination of the xylem vessels revealed notable differences between the grafting combination involving Bb and the rootstock F1 hybrid Be/Bb, compared to the one with To/Bb and the non-grafted Bb. Specifically, the area, diameter and number of xylem vessels were approximatively 45% higher in Be/Bb than in To/Bb and the non-grafted Bb. Furthermore, a robust linear correlation was observed between plant height with morphometric and physiological traits, except fruits sets. This study lays the basis for a novel protocol for agriculture, addressing the excessive vegetative growth in rootstocks regulating air and substrate temperatures.
Elucidating and Expanding the Restorative Theory Framework to Comprehend Influential Factors Supporting Ageing-in-Place: A Scoping Review
Authors: Grave Anne Johanna Jacoba , Neven Louis , Mohammadi Masi
Published: September 2023

Exposure to stress and attention fatigue resulting from changes in capabilities and residing in environments that do not align with individual needs can adversely impact older adults’ mental health and complicate ageing-in-place. Research into the psychological restoration process can help assist in alleviating these issues. Existing research on restoration perspectives has predominantly centred on university students and lacks comprehensive insights into older adults. Consequently, this study seeks to acquire a deeper understanding of the restorative theory framework within the context of ageing populations. We identified and analysed thirty-nine papers on the restoration process of older adults employing the scoping review method. Our findings indicate that adjustments to the general restorative theory framework are imperative for ageing populations. By incorporating additional features—such as being with and familiarity—the framework can more effectively support the development of age-inclusive neighbourhoods that enhance the mental health of the older population and facilitate healthy ageing-in-place. While more in-depth research is required on the restoration process of older adults, this research marks the initial in adapting the general framework to ageing populations. Furthermore, insight is given into how the adapted framework can contribute to help address the challenges of global ageing and support ageing-in-place.
Myogenetic Oligodeoxynucleotide Induces Myocardial Differentiation of Murine Pluripotent Stem Cells
Authors: Ishioka Mina , Nihashi Yuma , Sunagawa Yoichi , Umezawa Koji , Shimosato Takeshi , Kagami Hiroshi , Morimoto Tatsuya , Takaya Tomohide
Published: September 2023

An 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, acts as an anti-nucleolin aptamer and induces myogenic differentiation of skeletal muscle myoblasts. This study investigated the effect of iSN04 on murine embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In the undifferentiated state, iSN04 inhibited the proliferation of ESCs and iPSCs but did not affect the expression of pluripotent markers. In the differentiating condition, iSN04 treatment of ESCs/iPSCs from day 5 onward dramatically induced differentiation into Nkx2-5+ beating cardiomyocytes with upregulation of Gata4, Isl1, and Nkx2-5, whereas iSN04 treatment from earlier stages completely inhibited cardiomyogenesis. RNA sequencing revealed that iSN04 treatment from day 5 onward contributes to the generation of cardiac progenitors by modulating the Wnt signaling pathway. Immunostaining showed that iSN04 suppressed the cytoplasmic translocation of nucleolin and restricted it to the nucleoli. These results demonstrate that nucleolin inhibition by iSN04 facilitates the terminal differentiation of cardiac mesoderm into cardiomyocytes but interferes with the differentiation of early mesoderm into the cardiac lineage. This is the first report on the generation of cardiomyocytes from pluripotent stem cells using a DNA aptamer. Since iSN04 did not induce hypertrophic responses in primary-cultured cardiomyocytes, iSN04 would be useful and safe for the regenerative therapy of heart failure using stem cell-derived cardiomyocytes.
Immunosuppressive Therapy of Antibody-Mediated aHUS and TTP
Authors: Kelen Kata , Horváth Orsolya , Kis Éva , Mikes Bálint , Sallay Péter , Prohászka Zoltán , Szabó Attila József , Reusz György S.
Published: September 2023

The recent classification of pediatric thrombotic microangiopathies (TMA) takes into consideration mechanisms of disease for guidance to targeted therapies. We present our experience with seven patients with antibody mediated atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). Five children had aHUS with antibodies against complement factor H (CFH-ab) and two with TTP with antibodies against metalloproteinase ADAMTS13. In the aHUS cases diagnosed and treated before the eculizumab era, CFH-ab was detected using the ELISA assay. Mutational analysis of selected complement genes was performed. TTP was diagnosed if, in addition to microangiopathic hemolytic anemia and thrombocytopenia, ischemic organ involvement and severe deficiency in ADAMTS13 activity were present. Treatment protocol consisted of plasma exchanges (PE) and steroid pulses, followed by the combination of cyclophosphamide and rituximab to achieve long-term immunosuppression. Four patients with CFH-ab and the TTP patients with ADAMTS13 antibodies came into sustained remission. After a median follow-up of 11.7 (range 7.7–12.9) years without maintenance therapy, no disease recurrence was observed; nevertheless, six patients, two had hypertension and two had proteinuria as a late consequence. One patient, with late diagnosis of CFH-ab and additional genetic risk factors who was treated only with PE and plasma substitution, reached end-stage renal disease and was later successfully transplanted using eculizumab prophylaxis. In the cases of antibody-mediated TMAs, PE and early immunosuppressive treatment may result in sustained remission with preserved kidney function. Further data are needed to establish optimal treatment of anti-FH antibody-associated HUS.
Comparative Analysis of Different Proteins and Metabolites in the Liver and Ovary of Local Breeds of Chicken and Commercial Chickens in the Later Laying Period
Authors: Tang Yuan , Yin Lingqian , Liu Li , Chen Qian , Lin Zhongzhen , Zhang Donghao , Wang Yan , Liu Yiping
Published: September 2023

The liver and ovary perform a vital role in egg production in hens. In the later laying period, the egg-laying capacity of female hens, particularly that of local breeds, declines significantly. Hence, it is essential to study the features and conditions of the ovary and liver during this period. In this research, we characterized the proteins and metabolites in the liver and ovary of 55-week-old Guangyuan gray chickens (Group G) and Hy-Line gray chickens (Group H) by using liquid chromatography chip/electrospray ionization quadruple time-of-flight/mass spectroscopy (LC-MS/MS). In total, 139 differentially expressed proteins (DEPs) and 186 differential metabolites (DMs) were identified in the liver, and 139 DEPs and 36 DMs were identified in the ovary. The upregulated DEPs and DMs in both the liver and ovary of Group G were primarily enriched in pathways involved in amino acid and carbohydrate metabolism. This suggests that energy metabolism was highly active in the Guangyuan gray chickens. In contrast, the upregulated DEPs and DMs in Group H were mainly enriched in pathways associated with lipid metabolism, which may explain the higher egg production and the higher fatty liver rate in Hy-Line gray hens in the later laying period. Additionally, it was found that the unique protein s-(hydroxymethyl) glutathione dehydrogenase (ADH4) in Group G was implicated in functions such as fatty acid degradation, glycolysis, and pyruvate metabolism, whereas the unique proteins, steroid sulfatase (STS), glucosylceramidase (LOC107050229), and phospholipase A2 Group XV (PLA2G15), in Group H were involved in the metabolism of steroid hormones and glycerol phosphate. In conclusion, variations in how carbohydrates, lipids, and amino acids are processed in the liver and ovary of local breeds of chicken and commercial hens towards the end of their laying period could explain the disparities in their egg production abilities.
Physiological and Morphological Implications of Using Composts with Different Compositions in the Production of Cucumber Seedlings
Authors: Zapałowska Anita , Matłok Natalia , Piechowiak Tomasz , Szostek Małgorzata , Puchalski Czesław , Balawejder Maciej
Published: September 2023

Compost has a broad application in terms of the improvement of the soil properties. This research work was conducted to present the molecular implications of using compost obtained from different substrates to improve soil parameters for cucumber seedlings cultivation. In the experiment, the following compost mixtures were used: sewage sludge (80%) + sawdust (20%); sewage sludge (40%) + sawdust (10%) + biodegradable garden and park waste (50%); biodegradable garden and park waste (90%) + sawdust (10%); sewage sludge (80%) + sawdust (20%) + Eisenia fetida; sewage sludge (40%) + sawdust (10%) + biodegradable garden and park waste (50%) + Eisenia fetida; biodegradable garden and park waste (90%) + sawdust (10%) + Eisenia fetida. The final substrate compositions consisted of compost mixtures and deacidified peat(O) (pH 6.97; Corg content—55%, N content—2.3%), serving as a structural additive, in different mass ratios (mass %). The produced plants underwent biometric and physiological measurements as well as enzymatic analyses of stress markers. Based on the conducted studies, it has been found that the substrate productivity depends not only on the content of nutrient components but also on their structure, which is moderated by the proportion of peat in the substrate. The most effective and promising substrate for cucumber seedling production was variant 2 (I), which consisted of 25% compost from sewage sludge (40%) + sawdust (10%) + biodegradable garden and park waste (50%) and 75% deacidified peat. Despite the richness of the other substrates, inferior parameters of the produced seedlings were observed. The analysis of the enzymatic activity of stress markers showed that these substrates caused stress in the plants produced. The study’s results showed that this stress was caused by the presence of Eisenia fetida, which damaged the developing root system of plants in the limited volume of substrate (production containers). The adverse influence of Eisenia fetida on the plants produced could possibly be eliminated by thermal treatment of the compost, although this could lead to significant changes in composition.
Exploring the Complex and Multifaceted Interplay between Melanoma Cells and the Tumor Microenvironment
Authors: Kuras Magdalena
Published: September 2023

Malignant melanoma is a very aggressive skin cancer, characterized by a heterogeneous nature and high metastatic potential. The incidence of melanoma is continuously increasing worldwide, and it is one of the most common cancers in young adults. In the past twenty years, our understanding of melanoma biology has increased profoundly, and disease management for patients with disseminated disease has improved due to the emergence of immunotherapy and targeted therapy. However, a significant fraction of patients relapse or do not respond adequately to treatment. This can partly be explained by the complex signaling between the tumor and its microenvironment, giving rise to melanoma phenotypes with different patterns of disease progression. This review focuses on the key aspects and complex relationship between pathogenesis, genetic abnormalities, tumor microenvironment, cellular plasticity, and metabolic reprogramming in melanoma. By acquiring a deeper understanding of the multifaceted features of melanomagenesis, we can reach a point of more individualized and patient-centered disease management and reduced costs of ineffective treatments.
LOXL2 in Cancer: A Two-Decade Perspective
Authors: Cano Amparo , Eraso Pilar , Mazón María J. , Portillo Francisco
Published: September 2023

Lysyl Oxidase Like 2 (LOXL2) belongs to the lysyl oxidase (LOX) family, which comprises five lysine tyrosylquinone (LTQ)-dependent copper amine oxidases in humans. In 2003, LOXL2 was first identified as a promoter of tumour progression and, over the course of two decades, numerous studies have firmly established its involvement in multiple cancers. Extensive research with large cohorts of human tumour samples has demonstrated that dysregulated LOXL2 expression is strongly associated with poor prognosis in patients. Moreover, investigations have revealed the association of LOXL2 with various targets affecting diverse aspects of tumour progression. Additionally, the discovery of a complex network of signalling factors acting at the transcriptional, post-transcriptional, and post-translational levels has provided insights into the mechanisms underlying the aberrant expression of LOXL2 in tumours. Furthermore, the development of genetically modified mouse models with silenced or overexpressed LOXL2 has enabled in-depth exploration of its in vivo role in various cancer models. Given the significant role of LOXL2 in numerous cancers, extensive efforts are underway to identify specific inhibitors that could potentially improve patient prognosis. In this review, we aim to provide a comprehensive overview of two decades of research on the role of LOXL2 in cancer.
Finding Balance in Adversity: Nitrate Signaling as the Key to Plant Growth, Resilience, and Stress Response
Authors: Jia Yancong , Qin Debin , Zheng Yulu , Wang Yang
Published: September 2023

To effectively adapt to changing environments, plants must maintain a delicate balance between growth and resistance or tolerance to various stresses. Nitrate, a significant inorganic nitrogen source in soils, not only acts as an essential nutrient but also functions as a critical signaling molecule that regulates multiple aspects of plant growth and development. In recent years, substantial advancements have been made in understanding nitrate sensing, calcium-dependent nitrate signal transmission, and nitrate-induced transcriptional cascades. Mounting evidence suggests that the primary response to nitrate is influenced by environmental conditions, while nitrate availability plays a pivotal role in stress tolerance responses. Therefore, this review aims to provide an overview of the transcriptional and post-transcriptional regulation of key components in the nitrate signaling pathway, namely, NRT1.1, NLP7, and CIPK23, under abiotic stresses. Additionally, we discuss the specificity of nitrate sensing and signaling as well as the involvement of epigenetic regulators. A comprehensive understanding of the integration between nitrate signaling transduction and abiotic stress responses is crucial for developing future crops with enhanced nitrogen-use efficiency and heightened resilience.
High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by L-PRLR and S-PRLR
Authors: Yang Ruochen , Duan Chunhui , Zhang Shuo , Guo Yunxia , Shan Xinyu , Chen Meijing , Yue Sicong , Zhang Yingjie , Liu Yueqin
Published: September 2023

High prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study aimed to investigate the mechanism of apoptosis induced by high PRL concentration in GCs. Trial 1: The optimal concentration of glutathion was determined according to the detected cell proliferation. The results showed that the optimal glutathione concentration was 5 μmol/mL. Trial 2: 500 ng/mL PRL was chosen as the high PRL concentration. The GCs were treated with 0 ng/mL PRL (C group), 500 ng/mL PRL (P group) or 500 ng/mL PRL, and 5 μmol/mL glutathione (P-GSH group). The results indicated that the mitochondrial respiratory chain complex (MRCC) I–V, ATP production, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and thioredoxin peroxidase (TPx) in the C group were higher than those in the P group (p < 0.05), while they were lower than those in the P-GSH group (p < 0.05). Compared to the C group, the P group exhibited elevated levels of reactive oxygen species (ROS) and apoptosis (p < 0.05) and increased expression of ATG7 and ATG5 (p < 0.05). However, MRCC I–V, ATP, SOD, A-TOC, TPx, ROS, and apoptosis were decreased after the addition of glutathione (p < 0.05). The knockdown of either L-PRLR or S-PRLR in P group GCs resulted in a significant reduction (p < 0.05) in MRCC I–V, ATP, T-AOC, SOD and TPx, while the overexpression of either receptor showed an opposite trend (p < 0.05). Our findings suggest that high PRL concentrations induce apoptotic cell death in ovine ovarian GCs by downregulating L-PRLR and S-PRLR, activating oxidative stress and autophagic pathways.
Toward the Improvement of Maleic Anhydride Functionalization in Polyhydroxybutyrate (PHB): Effect of Styrene Monomer and Sn(Oct)2 Catalyst
Authors: de Souza Matheus Ferreira , Luna Carlos Bruno Barreto , Siqueira Danilo Diniz , Bezerra Ewerton de Oliveira Teotônio , de Cerqueira Grazielle Rozendo , Araújo Edcleide Maria , Wellen Renate Maria Ramos
Published: September 2023

In this work, polyhydroxybutyrate (PHB) was maleic anhydride (MA)-grafted in the molten state, using dicumyl peroxide (DCP) as a reaction initiator. Tin(II) 2-ethylhexanoate (Sn(Oct)2) and styrene monomer (St.) were used to maximize the maleic anhydride grafting degree. When PHB was modified with MA/DCP and MA/DCP/Sn(Oct)2, viscosity was reduced, suggesting chain scission in relation to pure PHB. However, when the styrene monomer was added, the viscosity increased due to multiple grafts of MA and styrene into the PHB chain. In addition, the FTIR showed the formation of a new band at 1780 cm−1 and 704 cm−1, suggesting a multiphase copolymer PHB-g-(St-co-MA). The PHB (MA/DCP) system showed a grafting degree of 0.23%; however, the value increased to 0.39% with incorporating Sn(Oct)2. The highest grafting efficiency was for the PHB (MA/DCP/St.) system with a value of 0.91%, while the PHB (MA/DCP/St./Sn(Oct)2) hybrid mixture was reduced to 0.73%. The chemical modification process of PHB with maleic anhydride increased the thermal stability by about 20 °C compared with pure PHB. The incorporation of 0.5 phr of the Sn(Oct)2 catalyst increased the efficiency of the grafting degree in the PHB. However, the St./Sn(Oct)2 hybrid mixture caused a deleterious effect on the maleic anhydride grafting degree.
Valorization Strategies in CO2 Capture: A New Life for Exhausted Silica-Polyethylenimine
Authors: Coralli Irene , Giuri Demetra , Spada Lorenzo , Ortolani Jacopo , Mazzocchetti Laura , Tomasini Claudia , Stevens Lee A. , Snape Colin E. , Fabbri Daniele
Published: September 2023

The search for alternative ways to give a second life to materials paved the way for detailed investigation into three silica-polyethylenimine (Si-PEI) materials for the purpose of CO2 adsorption in carbon capture and storage. A solvent extraction procedure was investigated to recover degraded PEIs and silica, and concomitantly, pyrolysis was evaluated to obtain valuable chemicals such as alkylated pyrazines. An array of thermal (TGA, Py-GC-MS), mechanical (rheology), and spectroscopical (ATR-FTIR, 1H-13C-NMR) methods were applied to PEIs extracted with methanol to determine the relevant physico-chemical features of these polymers when subjected to degradation after use in CO2 capture. Proxies of degradation associated with the plausible formation of urea/carbamate moieties were revealed by Py-GC-MS, NMR, and ATR-FTIR. The yield of alkylpyrazines estimated by Py-GC-MS highlighted the potential of exhausted PEIs as possibly valuable materials in other applications.
Surface Functionalisation of Self-Assembled Quantum Dot Microlasers with a DNA Aptamer
Authors: Charlton Bethan K. , Downie Dillon H. , Noman Isaac , Alves Pedro Urbano , Eling Charlotte J. , Laurand Nicolas
Published: September 2023

The surface functionalisation of self-assembled colloidal quantum dot supraparticle lasers with a thrombin binding aptamer (TBA-15) has been demonstrated. The self-assembly of CdSSe/ZnS alloyed core/shell microsphere-shape CQD supraparticles emitting at 630 nm was carried out using an oil-in-water emulsion technique, yielding microspheres with an oleic acid surface and an average diameter of 7.3 ± 5.3 µm. Surface modification of the microspheres was achieved through a ligand exchange with mercaptopropionic acid and the subsequent attachment of TBA-15 using EDC/NHS coupling, confirmed by zeta potential and Fourier transform IR spectroscopy. Lasing functionality between 627 nm and 635 nm was retained post-functionalisation, with oleic acid- and TBA-coated microspheres exhibiting laser oscillation with thresholds as low as 4.10 ± 0.37 mJ·cm−2 and 7.23 ± 0.78 mJ·cm−2, respectively.
Enhanced Antibacterial Ability of Electrospun PCL Scaffolds Incorporating ZnO Nanowires
Authors: Tian Jingjing , Paterson Thomas E. , Zhang Jingjia , Li Yingxing , Ouyang Han , Asencio Ilida Ortega , Hatton Paul V. , Zhao Yu , Li Zhou
Published: September 2023

The infection of implanted biomaterial scaffolds presents a major challenge. Existing therapeutic solutions, such as antibiotic treatment and silver nanoparticle-containing scaffolds are becoming increasingly impractical because of the growth of antibiotic resistance and the toxicity of silver nanoparticles. We present here a novel concept to overcome these limitations, an electrospun polycaprolactone (PCL) scaffold functionalised with zinc oxide nanowires (ZnO NWs). This study assessed the antibacterial capabilities and biocompatibility of PCL/ZnO scaffolds. The fabricated scaffolds were characterised by SEM and EDX, which showed that the ZnO NWs were successfully incorporated and distributed in the electrospun PCL scaffolds. The antibacterial properties were investigated by co-culturing PCL/ZnO scaffolds with Staphylococcus aureus. Bacterial colonisation was reduced to 51.3% compared to a PCL-only scaffold. The biocompatibility of the PCL/ZnO scaffolds was assessed by culturing them with HaCaT cells. The PCL scaffolds exhibited no changes in cell metabolic activity with the addition of the ZnO nanowires. The antibacterial and biocompatibility properties make PCL/ZnO a good choice for implanted scaffolds, and this work lays a foundation for ZnO NWs-infused PCL scaffolds in the potential clinical application of tissue engineering.
Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and Clinical Data
Authors: Villa Federica , Crippa Alessandra , Pelizzoni Davide , Ardizzoia Alessandra , Scartabellati Giulia , Corbetta Cristina , Cipriani Eleonora , Lavitrano Marialuisa , Ardizzoia Antonio
Published: September 2023

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6iss) are widely used in first-line metastatic breast cancer. For patients with progression under CDK4/6is, there is currently no standard treatment recommended at the category 1 level in international guidelines. The purpose of this article is to review the cellular mechanisms underlying the resistance to CDK4/6is, as well as treatment strategies and the clinical data about the efficacy of subsequent treatments after CDK4/6is-based therapy. In the first part, this review mainly discusses cell-cycle-specific and cell-cycle-non-specific resistance to CDK4/6is, with a focus on early and late progression. In the second part, this review analyzes potential therapeutic approaches and the available clinical data on them: switching to other CDK4/6is, to another single hormonal therapy, to other target therapies (PI3K, mTOR and AKT) and to chemotherapy.
Graph Convolutional Network and Contrastive Learning Small Nucleolar RNA (snoRNA) Disease Associations (GCLSDA): Predicting snoRNA–Disease Associations via Graph Convolutional Network and Contrastive Learning
Authors: Zhang Liangliang , Chen Ming , Hu Xiaowen , Deng Lei
Published: September 2023

Small nucleolar RNAs (snoRNAs) constitute a prevalent class of noncoding RNAs localized within the nucleoli of eukaryotic cells. Their involvement in diverse diseases underscores the significance of forecasting associations between snoRNAs and diseases. However, conventional experimental techniques for such predictions suffer limitations in scalability, protracted timelines, and suboptimal success rates. Consequently, efficient computational methodologies are imperative to realize the accurate predictions of snoRNA–disease associations. Herein, we introduce GCLSDA—graph Convolutional Network and contrastive learning predict snoRNA disease associations. GCLSDA is an innovative framework that combines graph convolution networks and self-supervised learning for snoRNA–disease association prediction. Leveraging the repository of MNDR v4.0 and ncRPheno databases, we construct a robust snoRNA–disease association dataset, which serves as the foundation to create bipartite graphs. The computational prowess of the light graph convolutional network (LightGCN) is harnessed to acquire nuanced embedded representations of both snoRNAs and diseases. With careful consideration, GCLSDA intelligently incorporates contrast learning to address the challenging issues of sparsity and over-smoothing inside correlation matrices. This combination not only ensures the precision of predictions but also amplifies the model’s robustness. Moreover, we introduce the augmentation technique of random noise to refine the embedded snoRNA representations, consequently enhancing the precision of predictions. Within the domain of contrast learning, we unite the tasks of contrast and recommendation. This harmonization streamlines the cross-layer contrast process, simplifying the information propagation and concurrently curtailing computational complexity. In the area of snoRNA–disease associations, GCLSDA constantly shows its promising capacity for prediction through extensive research. This success not only contributes valuable insights into the functional roles of snoRNAs in disease etiology, but also plays an instrumental role in identifying potential drug targets and catalyzing innovative treatment modalities.
The Biological Action and Structural Characterization of Eryngitin 3 and 4, Ribotoxin-like Proteins from Pleurotus eryngii Fruiting Bodies
Authors: Ragucci Sara , Landi Nicola , Citores Lucía , Iglesias Rosario , Russo Rosita , Clemente Angela , Saviano Michele , Pedone Paolo Vincenzo , Chambery Angela , Ferreras José Miguel , Di Maro Antimo
Published: September 2023

Ribotoxin-like proteins (RL-Ps) are specific ribonucleases found in mushrooms that are able to cleave a single phosphodiester bond located in the sarcin–ricin loop (SRL) of the large rRNA. The cleaved SRL interacts differently with some ribosomal proteins (P-stalk). This action blocks protein synthesis because the damaged ribosomes are unable to interact with elongation factors. Here, the amino acid sequences of eryngitin 3 and 4, RL-Ps isolated from Pleurotus eryngii fruiting bodies, were determined to (i) obtain structural information on this specific ribonuclease family from edible mushrooms and (ii) explore the structural determinants which justify their different biological and antipathogenic activities. Indeed, eryngitin 3 exhibited higher toxicity with respect to eryngitin 4 against tumoral cell lines and model fungi. Structurally, eryngitin 3 and 4 consist of 132 amino acids, most of them identical and exhibiting a single free cysteinyl residue. The amino acidic differences between the two toxins are (i) an additional phenylalanyl residue at the N-terminus of eryngitin 3, not retrieved in eryngitin 4, and (ii) an additional arginyl residue at the C-terminus of eryngitin 4, not retrieved in eryngitin 3. The 3D models of eryngitins show slight differences at the N- and C-terminal regions. In particular, the positive electrostatic surface at the C-terminal of eryngitin 4 is due to the additional arginyl residue not retrieved in eryngitin 3. This additional positive charge could interfere with the binding to the SRL (substrate) or with some ribosomal proteins (P-stalk structure) during substrate recognition.
Serum Complement C4 Levels Are a Useful Biomarker for Predicting End-Stage Renal Disease in Microscopic Polyangiitis
Authors: Matsuda Shogo , Oe Katsumasa , Kotani Takuya , Okazaki Ayana , Kiboshi Takao , Suzuka Takayasu , Wada Yumiko , Shiba Hideyuki , Hata Kenichiro , Shoda Takeshi , Takeuchi Tohru
Published: September 2023

This study aimed to evaluate the risk factors for end-stage renal disease (ESRD) in microscopic polyangiitis (MPA). In total, 74 patients with MPA were enrolled, and we compared the baseline clinical characteristics and disease activity between MPA patients who have progressed to ESRD and those without ESRD to select predictive factors for ESRD. Out of 74 patients, 12 patients (16.2%) had ESRD during follow-up. Serum C4 levels were significantly higher in MPA patients who have progressed to ESRD than in those without ESRD (p = 0.009). Multivariate analyses revealed that high serum creatinine levels (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.25–15.5) and high serum C4 levels (OR 1.24, 95% CI 1.03–1.49) were risk factors for ESRD. Using receiver operating characteristic analysis, the cut-off value for initial serum C4 levels and serum creatinine levels were 29.6 mg/dL and 3.54 mg/dL, respectively. Patients with MPA with a greater number of risk factors (serum C4 levels > 29.6 mg/dL and serum creatinine levels > 3.54 mg/dL) had a higher ESRD progression rate. Serum C4 levels were significantly positively correlated with serum creatinine levels and kidney Birmingham vasculitis activity score (p = 0.02 and 0.04, respectively). These results suggest that serum C4 levels are useful tools for assessing renal disease activity and prognosis in MPA.
Characterization and Comparative Analysis of the Complete Plastomes of Five Epidendrum (Epidendreae, Orchidaceae) Species
Authors: Zhao Zhuang , Zeng Meng-Yao , Wu Yu-Wei , Li Jin-Wei , Zhou Zhuang , Liu Zhong-Jian , Li Ming-He
Published: September 2023

Epidendrum, one of the three largest genera of Orchidaceae, exhibits significant horticultural and ornamental value and serves as an important research model in conservation, ecology, and evolutionary biology. Given the ambiguous identification of germplasm and complex evolutionary relationships within the genus, the complete plastome of this genus (including five species) were firstly sequenced and assembled to explore their characterizations. The plastomes exhibited a typical quadripartite structure. The lengths of the plastomes ranged from 147,902 bp to 150,986 bp, with a GC content of 37.16% to 37.33%. Gene annotation revealed the presence of 78–82 protein-coding genes, 38 tRNAs, and 8 rRNAs. A total of 25–38 long repeats and 130–149 SSRs were detected. Analysis of relative synonymous codon usage (RSCU) indicated that leucine (Leu) was the most and cysteine (Cys) was the least. The consistent and robust phylogenetic relationships of Epidendrum and its closely related taxa were established using a total of 43 plastid genomes from the tribe Epidendreae. The genus Epidendrum was supported as a monophyletic group and as a sister to Cattleya. Meanwhile, four mutational hotspots (trnCGCA–petN, trnDGUC–trnYGUA, trnSGCU–trnGUCC, and rpl32–trnLUAG) were identified for further phylogenetic studies. Our analysis demonstrates the promising utility of plastomes in inferring the phylogenetic relationships of Epidendrum.
SAFoldNet: A Novel Tool for Discovering and Aligning Three-Dimensional Protein Structures Based on a Neural Network
Authors: Petrovskiy Denis V. , Nikolsky Kirill S. , Rudnev Vladimir R. , Kulikova Liudmila I. , Butkova Tatiana V. , Malsagova Kristina A. , Kopylov Arthur T. , Kaysheva Anna L.
Published: September 2023

The development and improvement of methods for comparing and searching for three-dimensional protein structures remain urgent tasks in modern structural biology. To solve this problem, we developed a new tool, SAFoldNet, which allows for searching, aligning, superimposing, and determining the exact coordinates of fragments of protein structures. The proposed search and alignment tool was built using neural networking. Specifically, we implemented the integrative synergy of neural network predictions and the well-known BLAST algorithm for searching and aligning sequences. The proposed method involves multistage processing, comprising a stage for converting the geometry of protein structures into sequences of a structural alphabet using a neural network, a search stage for forming a set of candidate structures, and a refinement stage for calculating the structural alignment and overlap and evaluating the similarity with the starting structure of the search. The effectiveness and practical applicability of the proposed tool were compared with those of several widely used services for searching and aligning protein structures. The results of the comparisons confirmed that the proposed method is effective and competitive relative to the available modern services. Furthermore, using the proposed approach, a service with a user-friendly web interface was developed, which allows for searching, aligning, and superimposing protein structures; determining the location of protein fragments; mapping onto a protein molecule chain; and providing structural similarity metrices (expected value and root mean square deviation).
Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen
Authors: McBride David J. , Fielding Claire , Newington Taksina , Vatsiou Alexandra , Fischl Harry , Bajracharya Maya , Thomson Vicki S. , Fraser Louise J. , Fujita Pauline A. , Becq Jennifer , Kingsbury Zoya , Ross Mark T. , Moat Stuart J. , Morgan Sian
Published: September 2023

The collection of dried blood spots (DBS) facilitates newborn screening for a variety of rare, but very serious conditions in healthcare systems around the world. Sub-punches of varying sizes (1.5–6 mm) can be taken from DBS specimens to use as inputs for a range of biochemical assays. Advances in DNA sequencing workflows allow whole-genome sequencing (WGS) libraries to be generated directly from inputs such as peripheral blood, saliva, and DBS. We compared WGS metrics obtained from libraries generated directly from DBS to those generated from DNA extracted from peripheral blood, the standard input for this type of assay. We explored the flexibility of DBS as an input for WGS by altering the punch number and size as inputs to the assay. We showed that WGS libraries can be successfully generated from a variety of DBS inputs, including a single 3 mm or 6 mm diameter punch, with equivalent data quality observed across a number of key metrics of importance in the detection of gene variants. We observed no difference in the performance of DBS and peripheral-blood-extracted DNA in the detection of likely pathogenic gene variants in samples taken from individuals with cystic fibrosis or phenylketonuria. WGS can be performed directly from DBS and is a powerful method for the rapid discovery of clinically relevant, disease-causing gene variants.
Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy
Authors: Duchenne Jürgen , Larsen Camilla K. , Cvijic Marta , Galli Elena , Aalen John M. , Klop Boudewijn , Mirea Oana , Puvrez Alexis , Bézy Stéphanie , Wouters Laurine , Minten Lennert , Sirnes Per A. , Khan Faraz H. , Voros Gabor , Willems Rik , Penicka Martin , Kongsgård Erik , Hopp Einar , Bogaert Jan , Smiseth Otto A. , Donal Erwan , Voigt Jens-Uwe
Published: September 2023

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74–0.88) and 0.86 (95%CI: 0.79–0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12–0.67) to 0.20 (95%CI: 0.08–0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.
Impact on Endovascular Thrombectomy for Acute Ischemic Stroke of Aortic Arch Calcification on Chest X-ray
Authors: Jeong Hyeon Yeong , Nam Taek Min , Lee Sang Hyuk , Jang Ji Hwan , Kim Young Zoon , Kim Kyu Hong , Ryu Kyeong Hwa , Kim Do-Hyung , Kwan Byung Soo , Bak Hyerang , Kim Seung Hwan
Published: September 2023

Background: Vascular conditions can affect the recanalization rates after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Chest radiography can assess the conditions of the aortic arch based on the presence or absence of aortic arch calcification (AoAC). The aim of this study was to investigate the relationship between AoAC on chest radiography and first-pass successful recanalization (modified thrombolysis in cerebral infarction 2b/3 after the first-pass). Methods: We compared the rate of first-pass successful recanalization between patients with and without AoAC. A total of 193 patients with anterior circulation occlusion who underwent EVT between January 2017 and December 2021 were included. Results: AoAC was observed in 80 (41.5%) patients. Patients with AoAC were older (74.5 ± 7.78 vs. 63.9 ± 12.4 years, p < 0.001), had more EVT attempts (3.04 ± 1.95 vs. 2.01 ± 1.34 times, p < 0.001), and a longer procedural time (71.7 ± 31.2 vs. 48.7 ± 23.1 min, p < 0.001) than those without AoAC. Moreover, Patients with AoAC showed a lower incidence of first-pass successful recanalization (18.8% vs. 47.8%, p < 0.001) and a higher incidence of postprocedural hemorrhage (45.0% vs. 27.7%, p = 0.015) than those without AoAC. On multivariate analysis, AoAC was independently associated with first-pass successful recanalization (odds ratio: 0.239 [0.121–0.475], p < 0.001). Conclusions: AoAC on chest radiography can be used as a preoperative predictor of successful first-pass recanalization in patients undergoing EVT for AIS.
Effectiveness of Regular Aerobic Exercise in Improving Vascular Stiffness in Elderly Korean Women
Authors: Koh Suhan , Kim Taekyu , Kang Duwang , Kim Doyeon
Published: September 2023

The purpose of this study was to determine the effects of aerobic exercise on carotid to femoral pulse wave velocity (cf-PWV), cell adhesion molecules (intracellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), endothelial selectin (E-selectin), and oxidized LDL in elderly women aged 70–85 years, and to identify the effect of and correlation with vascular stiffness. Forty participants were recruited and divided into three groups; vascular stiffness (VSG, n = 14), obesity (OG, n = 14), and normal (NG, n = 12). All groups were given a 16-week intervention of aerobic exercise, and the data collected before and after exercise were analyzed using SPSS Ver. 23.0. Two-way repeated-measures ANOVA was used to evaluate between-group and time-dependent interaction effects. One-way ANOVA was used to evaluate between-group variations. In addition, the significance was tested using a post hoc test (Scheffe). The within-group variations by time before and after exercise were examined using a paired t-test, and correlation analysis was performed using Pearson correlation coefficients. Simple regression analysis was performed for variables showing significant differences. The results indicate interaction effects for cf-PWV (p < 0.001), VCAM-1 (p < 0.01), E-selectin (p < 0.05), and oxidized LDL (p < 0.001). The rate of change of cf-PWV was positively correlated with that of VCAM-1 (r = 0.352, p < 0.05) and that of oxidized LDL (r = 0.325, p < 0.05) with statistical significance. To determine the effect of the rate of change of cf-PWV on the rate of change of VCAM-1, the variables were tested, and the coefficient of determination in the regression analysis was 0.124, indicating that 12.4% of the tested variables fit the standard regression line. The variables for the effect of the rate of change of cf-PWV on the rate of change of oxidized LDL were also tested, and the coefficient of determination in the regression analysis was 0.106, indicating that 10.6% of the tested variables fit the standard regression line. Thus, the 16-week regular and consistent aerobic exercise program had significant effects on the cf-PWV, ICAM-1, VCAM-1, E-selectin, and oxidized LDL in elderly Korean women with vascular stiffness, suggesting improvements in vascular stiffness, based on which the intervention is predicted to contribute to the prevention of vascular dysfunction by lowering the risk of cardiovascular disease due to atherosclerosis, as well as having a positive effect in the prevention of impairment of vascular endothelial cells.
Magnetic Resonance Imaging Evaluation of Multifidus Muscle in Patients with Low Back Pain after Microlumbar Discectomy Surgery
Authors: Kose Halil Cihan , Aydin Serdar Onur
Published: September 2023

Cross-sectional area (CSA) and signal intensity ratio (SIR) of the multifidus muscle (MFM) on magnetic resonance imaging (MRI) was used to evaluate the extent of injury and atrophy of the MFM in patients with negative treatment outcomes following microlumbar discectomy (MLD). Negative treatment outcome was determined by pain score improvement of <50% compared to baseline. Patients in groups 1, 2, and 3 were evaluated at <4 weeks, 4–24 weeks, and >24 weeks postoperatively, respectively. The associations between the follow-up, surgery time and the changes in the MFM were evaluated. A total of 79 patients were included, with 22, 27, and 30 subjects in groups 1, 2, and 3, respectively. The MFM SIR of the ipsilateral side had significantly decreased in groups 2 (p = 0.001) and 3 (p < 0.001). The ipsilateral MFM CSA significantly decreased postoperatively in groups 2 (p = 0.04) and 3 (p = 0.006). The postoperative MRI scans found significant MFM changes on the ipsilateral side in patients with negative treatment outcomes regarding pain intensity following MLD. As the interval to the postoperative MRI scan increased, the changes in CSA of the MFM and change in T2 SIR of the MFM showed a tendency to increase.