Search Results (22)

This article focuses primarily on the current possibilities of using data and information from BIM models to estimate costs using identified methods and pricing systems for apartment buildings with different construction technologies. The authors analyse buildings with a built-up space of 3600–5300 m³, representing hundreds of projects currently available on the market. The applied methods include Pricing of Buildings Using a Spreadsheet Program, IFC-Supported Pricing Software, Pricing of Buildings in Design Software, and Pricing of Buildings Using a Design/Construction Library to compile cost estimates in the Czech URS, German Baupreislexikon, and British Spon’s Architects’ and Builders’ Price Book pricing systems. The usability of the BIM model with respect to the selected pricing system, construction technology, and methods ranges from 50% to 85%, with labour intensity ranging from 64 to 159 h. The key aspects for a wider application of BIM models include the completion of standardization at the level of graphic and non-graphic requirements related to the intended use of the data and information. The average cost per cubic metre of built-up space is EUR 469 in the Czech Republic, EUR 617 in Germany, and EUR 671 in Great Britain. This study brings new and distinctive insights compared to previous research by providing specific values for labour intensity and extractability, defining the limits of BIM use for cost estimation, and proposing recommendations to increase the applicability of the obtained data in practice. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized primarily by motor impairments due to the loss of dopaminergic neurons. Despite extensive research, the precise causes of PD remain unknown, and reliable non-invasive biomarkers are still lacking. This study aimed to explore gene expression profiles in peripheral blood to identify potential biomarkers for PD using machine learning approaches. We analyzed microarray-based gene expression data from 105 individuals (50 PD patients, 33 with other neurodegenerative diseases, and 22 healthy controls) obtained from the GEO database (GSE6613). Preprocessing was performed using the “affy” package in R with Expresso normalization. Feature selection and classification were conducted using a decision tree approach (C4.5/J48 algorithm in WEKA), and model performance was evaluated with 10-fold cross-validation. Additional classifiers such as Support Vector Machine (SVM), the Naive Bayes classifier and Multilayer Perceptron Neural Network (MLP) were used for comparison. ROC curve analysis and Gene Ontology (GO) enrichment analysis were applied to the selected genes. A nine-gene decision tree model (TMEM104, TRIM33, GJB3, SPON2, SNAP25, TRAK2, SHPK, PIEZO1, RPL37) achieved 86.71% accuracy, 88% sensitivity, and 87% specificity. The model significantly outperformed other classifiers (SVM, Naive Bayes, MLP) in terms of overall predictive accuracy. ROC analysis showed moderate discrimination for some genes (e.g., TRAK2, TRIM33, PIEZO1), and GO enrichment revealed associations with synaptic processes, inflammation, mitochondrial transport, and stress response pathways. Our decision tree model based on blood gene expression profiles effectively discriminates between PD, other neurodegenerative conditions, and healthy controls, offering a non-invasive method for potential early diagnosis. Notably, TMEM104, TRIM33, and SNAP25 emerged as promising candidate biomarkers, warranting further investigation in larger and synthetic datasets to validate their clinical relevance. Full article

Background/Objectives: The optimal healing process following root canal treatment involves biological apical sealing through new cementum formation. Bone morphogenetic protein 7 (BMP-7) has recently gained attention as a potential regulator of cementoblast differentiation and periodontal regeneration. However, its effects on periodontal ligament fibroblasts (PDLFs) and the underlying mechanisms remain incompletely understood. This study aimed to investigate whether BMP-7 induces cementoblast-like differentiation of PDLFs both in vivo and in vitro via the BMP-SMAD signaling pathway. Methods: In a rat pulpectomy model, root canals were treated with or without BMP-7 and examined histologically and immunohistochemically for F-spondin (Spon1) expression. In vitro, human PDLFs were stimulated with BMP-7, and analyses of mineralization, cementoblast marker expression, alkaline phosphatase activity, and SMAD-1/5/9 phosphorylation were conducted. Results: Immunohistochemical analysis revealed that Spon1-positive regions increased around the apical area following BMP-7 treatment, suggesting the induction of cementoblast-like differentiation. In vitro, BMP-7 enhanced the expression of cementoblast-associated genes and mineral deposition while activating SMAD-1/5/9 signaling. Phosphorylation was suppressed by the BMP receptor inhibitor LDN-193189, indicating canonical BMP-SMAD pathway involvement. Conclusions: Although the specific concentration range of maximal activity remains to be determined, the findings collectively suggest that BMP-7 can promote cementoblast-like differentiation of PDLFs and may contribute to apical healing through cementum-related mechanisms. These results provide mechanistic and biological insights that support the potential of BMP-7 as a modulator for biologically favorable periapical tissue regeneration following root canal therapy. Full article

Background: Frailty is an aging-associated syndrome involving a loss of physiological reserve and function, with decreased ability to recover from physical and psychosocial stress. However, the etiology and pathogenesis of frailty remain largely unknown. Aim: This study aimed to investigate key genes involved in frailty pathogenesis, exercise effects, and their contributions. Methods: We performed a weighted gene co-expression network analysis using a microarray dataset. By using the positive selection (PS), human accelerated region (HAR), and aging gene sets, we identified key genes for frailty and exercise-related genes. Results: We identified magenta and pink modules that have the most significant enrichments for the evolutionally elaborated genes. A functional enrichment analysis (FEA) revealed that genes related to redox-process regulation and extracellular-matrix organization were enriched in magenta and pink modules, respectively. We observed that six of the evolutionarily imprinted genes in the modules (MEOX2, PLCB4, LPAR6, SH3KBP1, APP and SPON1) were highly connected and showed signs of hub properties, which might play crucial roles in frailty- and exercise-related mechanisms. Conclusions: Further investigation into the functions of the identified modules and their member genes could aid in identifying diagnostic biomarkers and therapeutic targets for frailty. Full article

Background: Low birth weight in newborns is of multifactorial origin (fetal, maternal, placental, and environmental factors), and in one-third of cases, the cause is of unknown origin, with high infant morbidity and mortality. The main treatment for regaining weight and height in children with low birth weight is the application of growth hormones. However, their role as a protective factor to prevent an increase in body composition and the development of metabolic diseases is still poorly understood. Methodology: A case–control study was conducted in a cohort of patients consulted at the CES Pediatric Endocrinology Clinic, Medellín, Colombia, between 2008 and 2018. We evaluated sociodemographic and clinical variables. Additionally, the identification of differential patterns of genomic methylation between cases (treated with growth hormone) and controls (without growth hormone treatment) was performed. The groups were compared using Fisher’s exact test for qualitative variables and Student’s t-test for the difference in means in independent samples. The correlation was evaluated with the Pearson coefficient. Results: Regarding clinical manifestations, body mass index (BMI) was higher in children who did not receive growth hormone treatment, higher doses of growth hormone treatment helped reduce body mass index (R: −0.21, and p = 0.067), and the use of growth hormone was related to a decrease in triglyceride blood concentrations (p = 0.06); these results tended towards significance. Regarding genome-wide methylation patterns, the following genes were found to be hypermethylated: MDGA1, HOXA5, LINC01168, ZFYVE19, ASAH1, MYH15, DNAJC17, PAMR1, MROCKI, CNDP2, CBY2, ZADH2, HOOK2, C9orf129, NXPH2, OSCP1, ZMIZ2, RUNX1, PTPRS, TEX26, EIF2A4K, MYO1F, C2orf69, and ZSCAN1. Meanwhile, the following genes were found hypomethylated: C10orf71-AS1, ZDHHC13, RPL17, EMC4, RPRD2, OBSCN-AS1, ZNF714, MUC4, SUGT1P4, TRIM38, C3, SPON1, NGF-AS1, CCSER2, P2RX2, LOC284379, GGTA1, NLRP5, OR51A4, HLA-H, and TTLL8. Conclusions: Using growth hormone as a treatment in SGA newborns helps regain weight and height. Additionally, it could be a protective factor against the increase in adolescent body composition. Full article

Punctuation restoration plays an essential role in the postprocessing procedure of automatic speech recognition, but model efficiency is a key requirement for this task. To that end, we present EfficientPunct, an ensemble method with a multimodal time-delay neural network that outperforms the current best model by 1.0 F1 point while using less than a tenth of its network parameters for inference. This work further streamlines a speech recognizer and a BERT implementation to efficiently output hidden layer acoustic embeddings and text embeddings in the context of punctuation restoration. Here, forced alignment and temporal convolutions are used to eliminate the need for attention-based fusion, greatly increasing computational efficiency and improving performance. EfficientPunct sets a new state of the art with an ensemble that weighs BERT’s purely language-based predictions slightly more than the multimodal network’s predictions. Although EfficientPunct shows great promise, from a different perspective, to date, another important challenge in the field has been the fact that punctuation restoration models have been evaluated almost solely on well-structured, scripted corpora. However, real-world ASR systems and postprocessing pipelines typically apply to spontaneous speech with significant irregularities, stutters, and deviations from perfect grammar. To address this important discrepancy, we also introduce SponSpeech, a punctuation restoration dataset derived from informal speech sources, which includes punctuation and casing information. In addition to publicly releasing the dataset, the authors have contributed by providing a filtering pipeline that can be used to generate more data. This filtering pipeline examines the quality of both the speech audio and the transcription text. A challenging test set is also carefully constructed, aimed at evaluating the models’ ability to leverage audio information to predict, otherwise grammatically ambiguous, punctuation. SponSpeech has been made available to the public, along with all code for dataset building and model runs. Full article

Coronary artery disease (CAD) is linked to atherosclerosis plaque formation. In pro-inflammatory conditions, human Natural Killer (NK) cell frequencies in blood or plaque decrease; however, NK cells are underexplored in CAD pathogenesis, inflammatory mechanisms, and CAD comorbidities, such as human cytomegalovirus (HCMV) infection and diabetes. Analysis of PBMC CITE-seq data from sixty-one CAD patients revealed higher blood NK cell SPON2 expression in CAD patients with higher stenosis severity. Conversely, NK cell SPON2 expression was lower in pro-inflammatory atherosclerosis plaque tissue with an enriched adaptive NK cell gene signature. In CAD patients with higher stenosis severity, peripheral blood NK cell SPON2 expression was lower in patients with high HCMV-induced adaptive NK cell frequencies and corresponded to lower PBMC TGFβ transcript expression with dependency on diabetes status. These results suggest that high NK cell SPON2 expression is linked to atherosclerosis pro-homeostatic status and may have diagnostic and prognostic implications in cardiovascular disease. Full article

Purpose: To identify molecular changes during PCa invasion of adipose space using Spatial Transcriptomic Profiling of PCa cells. Methods: This study was performed on paired intraprostatic and extraprostatic samples obtained from radical prostatectomy with pT3a pathological stages. Results: Differential gene expression revealed upregulation of heat shock protein genes: DNAJB1, HSPA8, HSP90AA1, HSPA1B, HSPA1A in PCa PanCK+ cells from the adipose periprostatic space. Extraprostatic extension was significantly associated with overexpression of genes involved in metastatic spread (EGR1, OR51E2, SPON2), of aggressiveness ERG negative signature of enhancers of androgen receptor (HOXB13, FOXA1), and of PSMA (FOLH1). They were associated with loss at 6q, 10q, 16q, and gain at 8q24 locus. Conclusions: PCa invasion of adipose EPE induces adaptative process related to heat shock proteins; PCa cells in EPE also present transcriptomics signatures for ERG independent aggressiveness, androgen receptor co-activation, and specific CNV changes. Full article

Identifying influential nodes, with pivotal roles in practical domains like epidemic management, social information dissemination optimization, and transportation network security enhancement, is a critical research focus in complex network analysis. Researchers have long strived for rapid and precise identification approaches for these influential nodes that are significantly shaping network structures and functions. The recently developed SPON (sum of proportion of neighbors) method integrates information from the three-hop neighborhood of each node, proving more efficient and accurate in identifying influential nodes than traditional methods. However, SPON overlooks the heterogeneity of neighbor information, derived from the asymmetry properties of natural networks, leading to its lower accuracy in identifying essential nodes. To sustain the efficiency of the SPON method pertaining to the local method, as opposed to global approaches, we propose an improved local approach, called the SSPN (sum of the structural proportion of neighbors), adapted from the SPON method. The SSPN method classifies neighbors based on the h-index values of nodes, emphasizing the diversity of asymmetric neighbor structure information by considering the local clustering coefficient and addressing the accuracy limitations of the SPON method. To test the performance of the SSPN, we conducted simulation experiments on six real networks using the Susceptible–Infected–Removed (SIR) model. Our method demonstrates superior monotonicity, ranking accuracy, and robustness compared to seven benchmarks. These findings are valuable for developing effective methods to discover and safeguard influential nodes within complex networked systems. Full article

Chronic wounds and the failure of conventional treatment are relatively common in veterinary medicine. Recently, there has been a growing interest in alternative therapeutic approaches and the utilization of biodegradable materials. Their potential application in wound therapy may offer a novel and more suitable option compared to conventional treatment methods. Biodegradable materials can be classified into two main categories: natural, synthetic, and a combination of both, which have the potential to have synergistically enhanced properties. In this study, four domestic dogs with clinical symptoms of chronic wounds were enrolled. These wounds underwent treatment utilizing a novel biodegradable composite material composed of gelatin sponge combined with two electrospun layers of polycaprolactone (PCL) along with polyvinylpyrrolidone (PVP) fibers containing povidone-iodine complex (PVP-I). The initial phase of the study was dedicated to evaluating the antibacterial properties of iodine against Staphylococcus aureus and Escherichia coli. On average, wound healing in domestic dogs took 22 days from the initial treatment, and iodine concentrations demonstrated a significant antibacterial effect against Escherichia coli and Staphylococcus aureus. Based on the favorable outcomes observed in wound management, we believe that the utilization of a blend of natural and synthetic biodegradable materials holds promise as an effective wound therapy option. Full article

The estrogen metabolite 2-methoxyestradiol (2ME) is a promissory anticancer drug mainly because of its pro-apoptotic properties in cancer cells. However, the therapeutic use of 2ME has been hampered due to its low solubility and bioavailability. Thus, it is necessary to find new ways of administration for 2ME. Zeolites are inorganic aluminosilicates with a porous structure and are considered good adsorbents and sieves in the pharmaceutical field. Here, mordenite-type zeolite nanoparticles were loaded with 2ME to assess its efficiency as a delivery system for prostate cancer treatment. The 2ME-loaded zeolite nanoparticles showed an irregular morphology with a mean hydrodynamic diameter of 250.9 ± 11.4 nm, polydispersity index of 0.36 ± 0.04, and a net negative surface charge of −34 ± 1.73 meV. Spectroscopy with UV-vis and Attenuated Total Reflectance Infrared Fourier-Transform was used to elucidate the interaction between the 2ME molecules and the zeolite framework showing the formation of a 2ME-zeolite conjugate in the nanocomposite. The studies of adsorption and liberation determined that zeolite nanoparticles incorporated 40% of 2ME while the liberation of 2ME reached 90% at pH 7.4 after 7 days. The 2ME-loaded zeolite nanoparticles also decreased the viability and increased the mRNA of the 2ME-target gene F-spondin, encoded by SPON1, in the human prostate cancer cell line LNCaP. Finally, the 2ME-loaded nanoparticles also decreased the viability of primary cultures from mouse prostate cancer. These results show the development of 2ME-loaded zeolite nanoparticles with physicochemical and biological properties compatible with anticancer activity on the human prostate and highlight that zeolite nanoparticles can be a good carrier system for 2ME. Full article

We previously reported on the experimental validation of several in silico-predicted glioma biomarkers (e.g., Plexin-B2 (PLXNB2), SLIT3, and Spondin-1 (SPON1)) that were found to be higher in human high-grade gliomas (HGGs). In this study, we validated their therapeutic potential by investigating antibody therapies against these three biomarkers in a preclinical mouse GL261 high-grade glioma model. Efficacies for antibody therapies against these biomarkers were assessed by survival and tumor volumes, biomarker expressions, cell invasion and proliferation, and bioinformatics gene/protein associations. Antibodies against PLXNB2, SLIT3, or SPON1 were effective in significantly reducing tumor volumes and increasing animal survival. With immunohistochemistry (IHC), these biomarkers were highly expressed in human HGGs, as well as in mice tumors. From IHC, CD44v6 was significantly decreased for all three antibody treatments, compared to UT GL261 tumors. Bioinformatics suggested that targeting either PLXNB2 or SPON1 may have a major effect on HGG cell migration and invasion (validated with CD44v6 IHC), whereas targeting SLIT3, in addition to affecting cell invasion, may also affect cell proliferation (not validated with Ki67 IHC). These results indicate that targeting these three biomarkers could add to the therapeutic arsenal against high-grade gliomas and that antibodies against them could be considered for clinical translation. Full article

In animal models, the administration of ciliary neurotrophic factor (CNTF) was demonstrated to reduce bone mass and to participate in bone remodeling. Cementoblasts, a cell type embedded in the cementum, are the main cells to produce and mineralize the extracellular matrix. The effect of CNTF on cementoblasts has not yet been addressed. Thus, the goal of this in vitro study was to investigate possible influences of exogenous CNTF on cementogenesis, as well as autophagy regulation and subsequent mechanisms in cementoblasts. Cementoblasts (OCCM-30) were stimulated with exogenous CNTF. Alizarin Red staining was performed to analyze the functional differentiation (mineralization) of OCCM-30 cells. The release of OPG was quantified by ELISA. The expression of cementogenesis markers (RUNX-2, OCN, BMP-7, BSP, and SPON-2) was evaluated by RT-qPCR. Western blotting (WB) was performed for the protein expression of STAT3, COX-2, SHP-2, cPLAα, cPLAβ; ERK1/2, P38, and JNK. The autophagic flux was assessed using WB and RT-qPCR analysis of LC3A/B, Beclin-1, and Atg-5, and the autophagosome was investigated by immunofluorescence staining (IF). The ERK1/2 (FR180204) or STAT3 (sc-202818) antagonist was added, and the cellular response was analyzed using flow cytometry. Exogenous CNTF significantly attenuated mineralized nodule formation, impaired OPG release, and downregulated the mRNA levels of RUNX-2, OCN, BMP-7, and BSP. Moreover, CNTF induced the phosphorylation of STAT3 and activated a transient activation of SHP-2, cPLAβ, ERK1/2, P38, and JNK protein. CNTF also induced autophagosome formation and promoted autophagy-associated gene and protein expressions. Additionally, the inhibition of ERK1/2 or STAT3 reversed a CNTF-induced mineralization impairment and had regulatory effects on CNTF-induced autophagosome formation. Our data revealed that CNTF acts as a potent inhibitor of cementogenesis, and it can trigger autophagy, in part by ERK1/2 and STAT3 commitment in the cementoblasts. Thus, it may play an important role in inducing or facilitating inflammatory root resorption during orthodontic tooth movement. Full article

Gene structure alterations, such as chromosomal rearrangements that develop fusion genes, often contribute to tumorigenesis. It has been shown that the fusion genes identified in public RNA-sequencing datasets are mainly derived from intrachromosomal rearrangements. In this study, we explored fusion transcripts in clinical ovarian cancer specimens based on our RNA-sequencing data. We successfully identified an in-frame fusion transcript SPON1-TRIM29 in chromosome 11 from a recurrent tumor specimen of high-grade serous carcinoma (HGSC), which was not detected in the corresponding primary carcinoma, and validated the expression of the identical fusion transcript in another tumor from a distinct HGSC patient. Ovarian cancer A2780 cells stably expressing SPON1-TRIM29 exhibited an increase in cell growth, whereas a decrease in apoptosis was observed, even in the presence of anticancer drugs. The siRNA-mediated silencing of SPON1-TRIM29 fusion transcript substantially impaired the enhanced growth of A2780 cells expressing the chimeric gene treated with anticancer drugs. Moreover, a subcutaneous xenograft model using athymic mice indicated that SPON1-TRIM29-expressing A2780 cells rapidly generated tumors in vivo compared to control cells, whose growth was significantly repressed by the fusion-specific siRNA administration. Overall, the SPON1-TRIM29 fusion gene could be involved in carcinogenesis and chemotherapy resistance in ovarian cancer, and offers potential use as a diagnostic and therapeutic target for the disease with the fusion transcript. Full article

Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for DCN, EPHA4, FN1, SPON2, and SPP1, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs hsa-miR-200c and hsa-miR-146a significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for hsa-miR-29c. The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future. Full article