bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatopancreas Proteomic Analysis Reveals Key Proteins and Pathways in Regulatory of Ovary Maturation of Macrobrachium nipponense
Authors: Jiang Sufei , Qiao Hui , Fu Hongtuo , Gu Zemao
Published: March 2023

A TMT-based (Tandem Mass Tag) liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was employed to explore differentially expressed proteins (DEPs) and KEGG pathways in hepatopancreas of 5 ovary stages. In total, 17,999 peptides were detected, among which 3395 proteins were identified. Further analysis revealed 26, 24, 37, and 308 DEPs in HE-I versus HE-II, HE-II versus HE-Ⅲ, HE-Ⅲ versus HE-Ⅳ, and HE-Ⅳ versus HE-Ⅴ, respectively (HE-I, HE-II, HE-III, HE-IV, and HE-V means hepatopancreas sampled from ovary stage I to V.). Gene ontology (GO) analysis indicated that DEPs were significantly enriched in “catalytic activity”, “metabolic process”, and “cell” of 4 comparison groups in turn. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that in hepatopancreas, as the ovaries developed to maturation, carbohydrate metabolism, lipid metabolism, amino acid metabolism, and lysosome played important roles in turn. The mRNA expression of 15 selected DEPs were consistent with proteome results by qPCR analysis. Further mRNA expression investigation results suggested 4 proteins (fatty acid-binding protein, NPC intracellular cholesterol transporter 1, Serine hydroxymethyltransferase, and Crustapin) were involved in ovary maturation. These results enhance the understanding of the regulatory role of hepatopancreas in M. nipponense ovary maturation and provide new insights for understanding the crustacean regulation mechanisms.
Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients
Authors: Martínez-Casanova Javier , Esteve-Pitarch Erika , Colom-Codina Helena , Gumucio-Sanguino Víctor Daniel , Cobo-Sacristán Sara , Shaw Evelyn , Maisterra-Santos Kristel , Sabater-Riera Joan , Pérez-Fernandez Xosé L. , Rigo-Bonnin Raül , Tubau-Quintano Fe , Carratalà Jordi , Padullés-Zamora Ariadna
Published: March 2023

Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CLCR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT>1×MIC, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CLCR, but higher doses are needed for MIC = 16 mg/L when CLCR > 100 mL/min. For 100% fT>4×MIC, the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring.
Conjugation as a Tool in Therapeutics: Role of Amino Acids/Peptides-Bioactive (Including Heterocycles) Hybrid Molecules in Treating Infectious Diseases
Authors: Gattu Rohith , Ramesh Sanjay S. , Nadigar Siddaram , D Channe Gowda , Ramesh Suhas
Published: March 2023

Peptide-based drugs are gaining significant momentum in the modern drug discovery, which is witnessed by the approval of new drugs by the FDA in recent years. On the other hand, small molecules-based drugs are an integral part of drug development since the past several decades. Peptide-containing drugs are placed between small molecules and the biologics. Both the peptides as well as the small molecules (mainly heterocycles) pose several drawbacks as therapeutics despite their success in curing many diseases. This gap may be bridged by utilising the so called ‘conjugation chemistry’, in which both the partners are linked to one another through a stable chemical bond, and the resulting conjugates are found to possess attracting benefits, thus eliminating the stigma associated with the individual partners. Over the past decades, the field of molecular hybridisation has emerged to afford us new and efficient molecular architectures that have shown high promise in medicinal chemistry. Taking advantage of this and also considering our experience in this field, we present herein a review concerning the molecules obtained by the conjugation of peptides (amino acids) to small molecules (heterocycles as well as bioactive compounds). More than 125 examples of the conjugates citing nearly 100 references published during the period 2000 to 2022 having therapeutic applications in curing infectious diseases have been covered.
Anti-Biofilm Efficacy of Commonly Used Wound Care Products in In Vitro Settings
Authors: Regulski Matthew , Myntti Matthew F. , James Garth A.
Published: March 2023

Considering the prevalence and pathogenicity of biofilms in wounds, this study was designed to evaluate the anti-biofilm capabilities of eight commercially available wound care products using established in vitro assays for biofilms. The products evaluated included dressings with multiple delivery formats for ionic silver including nanocrystalline, gelling fibers, polyurethane (PU) foam, and polymer matrix. Additionally, non-silver-based products including an extracellular polymeric substance (EPS)-dissolving antimicrobial wound gel (BDWG), a collagenase-based debriding ointment and a fish skin-based skin substitute were also evaluated. The products were evaluated on Staphylococcus aureus and Pseudomonas aeruginosa mixed-species biofilms grown using colony drip flow reactor (CDFR) and standard drip flow reactor (DFR) methodologies. Anti-biofilm efficacy was measured by viable plate counts and confocal scanning laser microscopy (CSLM). Four of the eight wound care products tested were efficacious in inhibiting growth of new biofilm when compared with untreated controls. These four products were further evaluated against mature biofilms. BDWG was the only product that achieved greater than 2-log growth reduction (5.88 and 6.58 for S. aureus and P. aeruginosa, respectively) of a mature biofilm. Evaluating both biofilm prevention and mature biofilm disruption capacity is important to a comprehensive understanding of the anti-biofilm efficacy of wound care products.
Antioxidant, Anti-Inflammatory and Anti-Diabetic Activities of Tectona grandis Methanolic Extracts, Fractions, and Isolated Compounds
Authors: Han Mei , Yang Fengxian , Zhang Kun , Ni Jiyan , Zhao Xia , Chen Xuelin , Zhang Zhennan , Wang Hanlei , Lu Jing , Zhang Yumei
Published: March 2023

Tectona grandis is a traditional Dai medicine plant belonging to the Lamiaceae family, which can be used to treat malaria, inflammation, diabetes, liver disease, bronchitis, tumors, cholelithiasis, jaundice, skin disease and as an anti-helminthic. To find more novel therapeutic agents contained in this medicinal plant, the antioxidant, anti-inflammatory and anti-diabetic activities of T. grandis methanolic extract, fractions and compounds were evaluated. In this study, 26 compounds were isolated from the leaves and branches of T. grandis. Their structures were identified based on extensive spectral experiments, including NMR, ESI-MS and comparison with published spectral data. Among them, compounds 1–2, 4–6, 9–14 and 16–22 were reported for the first time for this plant. The antioxidant activity screening results showed that compounds 5, 15 and 23 had potent antioxidant capacities, with SC50 values from 0.32 to 9.92 µmol/L, 0.92 to 1.10 mmol Trolox/L and 1.02 to 1.22 mmol Trolox/L for DPPH, ABTS and FRAP, respectively. In addition, their anti-inflammatory effects were investigated by releasing TNF-α, IL-1β and IL-6 through the use of mouse monocytic macrophages (RAW 264.7). Compounds 1, 13, 18 and 23 had the effects of reducing the expression of inflammatory factors. Compounds 13 and 18 were reported for the first time for their anti-inflammatory activities. Furthermore, the methanolic extract (ME), petroleum ether extract (PEE) and EtOAc extract (EAE) of T. grandis showed significant glucose uptake activities; compounds 21 and 23 significantly promoted glucose uptake of 3T3-L1 adipocytes at 40 µM. Meanwhile, compounds 4, 5 and 7 showed significant inhibitory activities against α-glucosidase, with IC50 values of 14.16 ± 0.34 µmol/L, 19.29 ± 0.26 µmol/L and 3.04 ± 0.08 µmol/L, respectively. Compounds 4 and 5 were reported for the first time for their α-glucosidase inhibitory activities. Our investigation explored the possible therapeutic material basis of T. grandis to prevent oxidative stress and related diseases, especially inflammation and diabetes.
Research on Intelligent Perception Algorithm for Sensitive Information
Authors: Huo Lin , Jiang Juncong
Published: March 2023

In the big data era, a tremendous volume of electronic documents is transmitted via the network, many of which include sensitive information about the country and businesses. There is a pressing need to be able to perform intelligent sensing of sensitive information on these documents in order to be able to discover and guarantee the security of sensitive information in this enormous volume of documents. Although the low effectiveness of manual detection is resolved by the current method of handling sensitive information, there are still downsides, such as poor processing effects and slow speed. This study creatively proposes the Text Sensitive Information Intelligent Perception algorithm (TSIIP), which detects sensitive words at the word level and sensitive statements at the statement level to obtain the final assessment score of the text. We experimentally compare this algorithm with other methods on an existing dataset of sensitive Chinese information. We use the metrics measuring the accuracy of the binary classification model, where the F1 score reaches 0.938 (+0.6%), and the F2 score reaches 0.946 (+1%), and the experimental results fully demonstrate the superiority of this algorithm.
Investigating Salinity Effects in Brackish Aquaponics Systems: Evidencing the Co-Cultivation of the Halophyte Crithmum maritimum with the Euryhaline Sparus aurata
Authors: Vlahos Nikolaos , Berillis Panagiotis , Levizou Efi , Patsea Efstathia , Panteli Nikolas , Demertzioglou Maria , Morfesis Konstantinos , Voudouri Georgia , Krigas Nikos , Kormas Kostantinos , Antonopoulou Efthimia , Mente Eleni
Published: March 2023

The possibility of simultaneous production of halophyte and euryhaline fish creates huge interest in both commercial aquaponics systems and in research. The aim of the present study was to investigate the effect of three different salinities (8, 14, and 20 ppt) on the growth performance and survival rate of sea bream (Sparus aurata) and rock samphire (Crithmum maritimum) in an experimental brackish aquaponic system. Furthermore, induction of heat shock proteins (Hsps) and phosphorylation of mitogen-activated protein kinases (MAPKs) were assessed through the sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis. A total number of 234 sea bream individuals were divided into nine autonomous aquaponic systems. The experiment lasted 45 days. In total, 54 individuals of rock samphire were used and were distributed into groups of six individuals per hydroponic tank using the raft method. Water quality showed stable fluctuation throughout the experiment, strongly supporting fish and plant growth performance and survival in both treatments. The results show that better growth performance for both sea bream and rock samphire (height increase) was evident in salinity 8 ppt compared to salinities 14 ppt and 20 ppt. Minimal or mild histopathological alterations were detected in gills, midgut, and liver for all three salinity groups. Exposure to different salinities modified Hsp60 and MAPKs expression in a tissue- and time-specific manner. During exposure to 8 ppt, constant Hsp60 levels and phosphorylation of MAPKs at 15 days may indicate a prominent protective role in the gills. The results show that sea bream and rock samphire can be used in brackish aquaponics systems with satisfactory growth performances, thus allowing for a range of commercial applications generating interest in their production.
Verification of Characteristics of Spline Filter Series Robust Filters for Surface Roughness and Proposal of Filter Selection Guidelines
Authors: Kondo Yuki , Yoshida Ichiro , Numada Munetoshi , Koshimizu Hiroyasu , Saito Ryo , Fujiyoshi Kaito
Published: March 2023

In surface roughness measurements, the presence of spikes in the primary profile can disable a normal filter from extracting the shape and waviness components. The robust spline filter (RSF) has been proposed to solve this problem. However, because ISO 16610-32, an RSF standard, has a significant deficiency, it was withdrawn in the Technical Specifications stage. The other proposed RSFs only show the method and a few examples with normal roughness and spike. Therefore, because the characteristics of each RSF have not been clarified, which RSF should be used for which primary profiles is not clear. This is one of the reasons for the delay in establishing ISO. In addition, the measurement sites need the establishment of robust spline filter selection guidelines. Therefore, in this paper, the characteristics of RSFs are clarified. Additionally, the points to be considered in using RSFs are summarized. Finally, the filter that should be selected for the specific application is identified. These results are expected to contribute to the widespread use of RSFs in the industrial world, avoid confusion at the measurement site, and help establish a new RSF standard.
A Method of Aerial Multi-Modal Image Registration for a Low-Visibility Approach Based on Virtual Reality Fusion
Authors: Wu Yuezhou , Liu Changjiang
Published: March 2023

Aiming at the approach and landing of an aircraft under low visibility, this paper studies the use of an infrared heat-transfer imaging camera and visible-light camera to obtain dynamic hyperspectral images of flight approach scenes from the perspective of enhancing pilot vision. Aiming at the problems of affine deformation, difficulty in extracting similar geometric features, thermal shadows, light shadows, and other issues in heterogenous infrared and visible-light image registration, a multi-modal image registration method based on RoI driving in a virtual scene, RoI feature extraction, and virtual-reality-fusion-based contour angle orientation is proposed, and this could reduce the area to be registered, reduces the amount of computation, and improves the real-time registration accuracy. Aiming at the differences in multi-modal image fusion in terms of resolution, contrast, color channel, color information strength, and other aspects, the contour angle orientation maintains the geometric deformation of multi-source images well, and the virtual reality fusion technology effectively deletes incorrectly matched point pairs. By integrating redundant information and complementary information from multi-modal images, the visual perception abilities of pilots during the approach process are enhanced as a whole.
On the Association between Dental Implants, Osteoporosis and Bone Modulating Therapy
Authors: Masri Daya , Masri-Iraqi Hiba , Nissan Joseph , Naishlos Sarit , Ben-Zvi Yehonthan , Rosenfeld Eli , Avishai Gal , Chaushu Liat
Published: March 2023

Background: Osteoporosis affects bone metabolism and may result in fragility fractures. Medications include bone modulating therapy (BMT), which come with the risk of osteonecrosis of the jaws (ONJ). The literature is contradictory about the impact of osteoporosis and/or BMT on dental implant success and the incidence of ONJ. Purpose: The aim of the present study was to assess the effect of osteoporosis and BMT on early implant failure (EIF) and ONJ incidence (primary outcome parameters) following dental implant placement. Materials and Methods: Retrospective, cohort study based on dental records. Implant-supported prostheses (ISP) were delivered by experienced oral and maxillofacial surgeons and prosthodontists. Inclusion criteria: diagnosis of osteoporosis, delivery of ISP, consecutive individuals, and available data. Confounding variables included—age, gender, smoking status, BMT, bone grafting, and implant length/diameter. Results: There were a total of 72 osteoporosis patients, 46 using and 26 not using BMT. There were a total of 279 inserted implants, 154 in those using and 124 in those not using BMT. Univariate analysis of factors that may affect EIF showed no statistically significant differences between non-osteoporotic, osteoporotic using BMT, and osteoporotic patients not using BMT regarding EIF and ONJ incidence following dental implant delivery. Multivariate model using logistic regression demonstrated one factor associated with increased risk for EIF—bone augmentation. No cases of ONJ were reported up to one year post ISP delivery in any group. Conclusions: Within the limitations of the present study, it can be concluded that installing dental implants in osteoporotic patients, treated or not with BMT, is a safe procedure with EIF comparable to non-osteoporotic patients. The short-term risk for ONJ following dental implant insertion in osteoporotic (even when using BMT) patients is negligible.
A Data Factor Study for Machine Learning on Heterogenous Edge Computing
Authors: Chang Dong-Meau , Hsu Tse-Chuan , Yang Chao-Tung , Yang Junjie
Published: March 2023

As plants and animals grow, there are many factors that influence the changes that will affect how plants grow and how botanical experts distinguish them. The use of the Internet of Things (IoT) for data collection is an important part of smart agriculture. Many related studies have shown that remote data management and cloud computing make it possible and practical to monitor the functionality of IoT devices. In automated agriculture, machine learning intelligence is more necessary to use to automatically determine whether the correlation between learning factors influences plant growth patterns. In this research experiment, the relevant data are automatically collected through a detection device, and data modeling and computation are performed in an edge computing environment. At the same time, the data model is transmitted via the communication protocol, and another node is available for verification of the modeling and calculation results. The experimental results show that the single-point data-trained model is able to accurately predict the growth trend of the plants. In the case of verification of the second measurement point at a different space, the data model must be trained with more than two layers in order to improve the training results and reduce errors.
Impact of Stabilization Method and Filtration Step on the Ester Profile of “Brandy de Jerez”
Authors: Muñoz-Redondo José Manuel , Puertas Belén , Valcárcel-Muñoz Manuel José , Rodríguez-Solana Raquel , Moreno-Rojas José Manuel
Published: March 2023

Brandy stabilization is an important step aimed at decanting the suspended organic and inorganic particles that may cause undesirable turbidity (cloudiness or haze) in brandies, affecting the physico-chemical stability, the organoleptic characteristics, and the consumer’s quality perception of the brandy. This phenomenon originates from insoluble salts, volatile compounds (higher alcohols, fatty acid esters, and others), and ethanol-soluble lignins. Among them, ethyl esters of long-chain fatty acids are considered the main cause of haze formation, due to a decrease in their solubility when brandies are stored at low temperatures. For this reason, producers are recommended to intentionally encourage the formation of haze and then to remove it before releasing the brandy to the market. The purpose of this work was to study the influence of two methods of stabilization, the traditional method at room temperature for 1 year, and cold stabilization for 7 days at −10 °C, on the ester profile of “Brandy de Jerez”. The results were compared with non-stabilized samples, to determine the main changes in the volatile composition. The use of multivariate statistical analyses made it possible to identify the esters (potential markers) most impacted by the stabilization process. It was observed that traditional stabilization yielded the most distinct ester profile, while brandies stabilized at cold temperature displayed a lower impact on their volatile composition. Furthermore, both stabilization processes produced a significant decrease in ethyl esters of long-chain fatty acids, which are the compounds responsible for haze formation.
Fascination with Fluctuation: Luria and Delbrück’s Legacy
Authors: Robeva Raina S. , Jungck John R.
Published: March 2023

While Luria and Delbrück’s seminal work has found its way to some college biology textbooks, it is now largely absent from those in mathematics. This is a significant omission, and we consider it a missed opportunity to present a celebrated conceptual model that provides an authentic and, in many ways, intuitive example of the quantifiable nature of stochasticity. We argue that it is an important topic that could enrich the educational literature in mathematics, from the introductory to advanced levels, opening many doors to undergraduate research. The paper has two main parts. First, we present in detail the mathematical theory behind the Luria–Delbrück model and make suggestions for further readings from the literature. We also give ideas for inclusion in various mathematics courses and for projects that can be used in regular courses, independent projects, or as starting points for student research. Second, we briefly review available hands-on activities as pedagogical ways to facilitate problem posing, problem-based learning, and investigative case-based learning and to expose students to experiments leading to Poisson distributions. These help students with even limited mathematics backgrounds understand the significance of Luria–Delbrück’s work for determining mutation rates and its impact on many fields, including cancer chemotherapy, antibiotic resistance, radiation, and environmental screening for mutagens and teratogens.
Development of a Metaphyseal Non-Union Model in the Osteoporotic Rat Femur
Authors: Deluca Amelie , Wagner Andrea , Faustini Bettina , Weissenbacher Nadja , Deininger Christian , Wichlas Florian , Tempfer Herbert , Mueller Ernst J. , Traweger Andreas
Published: March 2023

The aim of this current study was to establish a metaphyseal femoral non-union model in osteoporotic rats by comparing a power tool versus a manual tool for fracture creation. Twelve adult female Sprague Dawley rats were ovariectomized (OVX) and received a special diet for 6 weeks. Biweekly pQCT measurements confirmed a significant reduction in the cancellous and total bone mineral density in OVX rats compared to control (CTRL) animals. After 6 weeks, OVX rats underwent surgery creating a distal metaphyseal osteotomy, either using a piezoelectric- (n = 6) or a manual Gigli wire (n = 6) saw. Fractures were stabilized with a Y-shaped mini-locking plate. Within each group, three rats received Alginate directly into the fracture gap. OVX animals gained more weight over 8 weeks compared to CTRL animals. pQCT analysis showed a significant difference in the volumetric cancellous bone mineral density between OVX and CTRL rats. A histological examination of the osteoporotic phenotype was completed. Radiographic evaluation and Masson–Goldner trichrome staining with the piezoelectric saw failed to demonstrate bony bridging or a callus formation. New bone formation and complete healing were seen after 6 weeks in the Gigli group. For the creation of a metaphyseal atrophic non-union in the osteoporotic bone, a piezoelectric saw should be used.
On the Best Way to Cluster NCI-60 Molecules
Authors: Hernández-Hernández Saiveth , Ballester Pedro J.
Published: March 2023

Machine learning-based models have been widely used in the early drug-design pipeline. To validate these models, cross-validation strategies have been employed, including those using clustering of molecules in terms of their chemical structures. However, the poor clustering of compounds will compromise such validation, especially on test molecules dissimilar to those in the training set. This study aims at finding the best way to cluster the molecules screened by the National Cancer Institute (NCI)-60 project by comparing hierarchical, Taylor–Butina, and uniform manifold approximation and projection (UMAP) clustering methods. The best-performing algorithm can then be used to generate clusters for model validation strategies. This study also aims at measuring the impact of removing outlier molecules prior to the clustering step. Clustering results are evaluated using three well-known clustering quality metrics. In addition, we compute an average similarity matrix to assess the quality of each cluster. The results show variation in clustering quality from method to method. The clusters obtained by the hierarchical and Taylor–Butina methods are more computationally expensive to use in cross-validation strategies, and both cluster the molecules poorly. In contrast, the UMAP method provides the best quality, and therefore we recommend it to analyze this highly valuable dataset.
Molecular Investigation of DKK3 in Cerebral Ischemic/Reperfusion Injury
Authors: Caffo Maria , Fusco Roberta , Siracusa Rosalba , Caruso Gerardo , Barresi Valeria , Di Paola Rosanna , Cuzzocrea Salvatore , Germanò Antonino Francesco , Cardali Salvatore Massimo
Published: March 2023

Dickkopf-3 (Dkk3) is an atypical member of the Dkk family of Wnt inhibitors, which has been implicated in the pathophysiology of neurodegenerative disorders. Its role in the mechanisms of cellular degeneration and protection is still unknown. The aim of our work is to investigate the endogenous activation of the DKK3 pathway in a model of transient occlusion of the middle cerebral artery in rats. In particular, the animals were subjected to 1 h of ischemia followed by different reperfusion times (1 h, 6 h, 12 h and 24 h) to evaluate the downstream pathway and the time course of its activation. Western blot analysis showed increased Dkk3 expression in animals with the highest time of reperfusion. The increased levels of Dkk3 were accompanied by reduced Wnt3a, Frz1 and PIWI1a expression in the cytosol while FOXM1 and β-catenin decreased in the nucleus. These molecular changes led to an increase in the apoptotic pathway, as showed by the increased expression of Caspase 3 and Bax and the reduced levels of Bcl-2, and to a decrease in neurogenesis, as shown by the decreased expression of Tbr2, Ngn2 and Pax6. In the second part of the study, we decided to employ curcumin, an activator of the Wnt/β-catenin signaling, to investigate its effect on Dkk3. In particular, curcumin was administered 1 and 6 h after ischemia, and animals were sacrificed 24 h later when the expression of Dkk3 was higher. Our data displayed that curcumin administration decreased Dkk3 expression, and increased Wnt3a, Frz1 and PIWI1a levels. Well in line with these data, curcumin administration increased nuclear β-catenin and FOXM1 expression. The down-regulation of Dkk3 by curcumin led to reduced apoptosis and increased neurogenesis. Summarizing, our results showed that Dkk3 acts as an inhibitor of Wnt/β-catenin signaling during cerebral ischemia. Additionally, its inhibition and the contextual activation of the Wnt/β-catenin pathway are protective against ischemic stroke.
Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience
Authors: Coutanceau Bérangère , Dos Santos Esther , Swierkowski Blanchard Nelly , Sanchez Louboutin Anne , Boitrelle Florence , Margueritte François , Vialard François , Serazin Valérie , Fathallah Khadija
Published: March 2023

Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide.
A Novel Method in Identifying Pyroptosis and Apoptosis Based on the Double Resonator Piezoelectric Cytometry Technology
Authors: Li Wenwei , Li Jing , Wu Yanyang , Zhou Tiean
Published: March 2023

In this study, a double resonator piezoelectric cytometry (DRPC) technology based on quartz crystal microbalance (QCM) was first employed to identify HeLa cell pyroptosis and apoptosis by monitoring cells’ mechanical properties in a real-time and non-invasive manner. AT and BT cut quartz crystals with the same frequency and surface conditions were used concurrently to quantify the cells-exerted surface stress (ΔS). It is the first time that cells-exerted surface stress (ΔS) and cell viscoelasticity have been monitored simultaneously during pyroptosis and apoptosis. The results showed that HeLa pyroptotic cells exerted a tensile stress on quartz crystal along with an increase in the elastic modulus (G′), viscous modulus (G″), and a decrease of the loss tangent (G″/G′), whereas apoptotic cells exerted increasing compressive stress on quartz crystal along with a decrease in G′, G″ and an increase in G″/G′. Furthermore, engineered GSDMD−/−-DEVD- HeLa cells were used to investigate drug-induced disturbance and testify the mechanical responses during the processes of pyroptosis and non-pyroptosis. These findings demonstrated that the DRPC technology can serve as a precise cytomechanical sensor capable of identifying pyroptosis and apoptosis, providing a novel method in cell death detection and paving the road for pyroptosis and apoptosis related drug evaluation and screening.
A Qualitative Investigation of the Obstacles Inherent in the Implementation of Building Information Modeling (BIM)
Authors: Altassan Abdulrahman , Othman Mahmoud , Elbeltagi Emad , Abdelshakor Mohammed , Ehab A.
Published: March 2023

The Middle East construction industry is fragmented, which makes project data inaccessible and underutilized. Building information modeling (BIM) provides innovative solutions to the AEC industry. Due to a lack of awareness of BIM’s successful processes, protocols, and workflows, some Middle Eastern organizations have tried to create their own systems but have not always chosen BIM. Some users did not comprehend BIM’s benefits, and the construction business was not ready for BIM technology. Furthermore, BIM’s benefits were not well known. This study intends to investigate construction practitioners’ awareness of the BIM field, the BIM adoption situation, and procedures in Middle Eastern design companies, by identifying and assessing construction professionals’ perceptions of impediments to BIM implementation in Middle Eastern construction. This research conducted a semi-structured interview to collect data and information from design teams currently adopting BIM at the project design stage. Thirteen of thirty-nine accepted to participate, with four invalid samples. Data collection reached a saturation point after the fifth interview. The descriptive and empirical analysis showed few BIM studies, lack of knowledge, insufficient government policies, high implementation costs, inadequate contractual coordination, lack of specified standards, cost of data and information sharing, technological availability issues, stakeholder reluctance, business and cultural changes, data and intellectual property issues, and interoperability issues. The factor analysis identified three main BIM implementation difficulties in Middle Eastern construction. These factors are training, cost, and economic constraints.
Exploring Leaders’ Perceptions of the Business Case for Digitalisation in the Construction Industry
Authors: Zulu Sambo Lyson , Saad Ali M. , Gledson Barry
Published: March 2023

For decision-makers in construction organisations, it is imperative that persuasive business cases are formulated on matters of digital transformation. In fact, a link has been established between the low adoption of digitalisation in construction organisations and poor business case formation. Therefore, the purpose of this paper is to explore the cues that may facilitate the development of such a business case responsible for wider adoption. (1) Methodology: We utilised a purposive sampling method to gather qualitative data from 19 leaders of UK construction organisations. Analysis of the semi-structured interviews involves a thematic analysis through an inductive approach. (2) Findings: Overall, this exploration led to the emergence of nine themes, informing research on aspects that may contribute to substantiating a compelling business case behind the broader use of digitalisation in construction firms. The findings suggest that embracing such arguments would enable digital advocates to craft compelling arguments that may persuade decision-makers towards digitalisation. (3) Originality: This is the first paper in the construction domain to explore how building a robust business case that can justify adoption, offering digital advocates a set of cues that can be used to develop a successful relational capability to advance with their digital agendas. Thus, this study is a unique contribution to the literature, offering evidence that is otherwise understudied in the construction context.
Unsteady Heat Flux Measurement and Predictions Using Long Short-Term Memory Networks
Authors: Park Byung , Kim Charn-Jung
Published: March 2023

Energy consumption modeling has evolved along with building technology. Modeling techniques can be largely classified into white box, gray box, and black box. In this study, the thermal behavior characteristics of building components were identified through time-series data analysis using LSTM neural networks. Sensors were installed inside and outside the test room to measure physical quantities. As a result of calculating the overall heat transfer coefficient according to the international standard ISO 9869-1, the U value of the multi-window with antireflection coating was 1.84 W/(m2∙K). To understand the thermal behavior of multiple windows, we constructed a neural network using an LSTM architecture and used the measured data-set to predict and evaluate the heat flux through deep learning. From the measurement data, a wavelet transform was used to extract features and to find appropriate control time-step intervals. Performance was evaluated according to multistep measurement intervals using the error metric method. The multistep time interval for control monitoring is preferably no more than 240 s. In addition, multivariate analysis with several input variables was performed. In particular, the thermal behavior of building components can be analyzed through heat flux and temperature measurements in the transient state of physical properties of pre-installed building components, which were difficult to access with conventional steady-state measurement methods.
Biological Role and Clinical Implications of MYOD1L122R Mutation in Rhabdomyosarcoma
Authors: Di Carlo Daniela , Chisholm Julia , Kelsey Anna , Alaggio Rita , Bisogno Gianni , Minard-Colin Veronique , Jenney Meriel , Dávila Fajardo Raquel , Merks Johannes H. M. , Shipley Janet M. , Selfe Joanna L.
Published: March 2023

Major progress in recent decades has furthered our clinical and biological understanding of rhabdomyosarcoma (RMS) with improved stratification for treatment based on risk factors. Clinical risk factors alone were used to stratify patients for treatment in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 protocol. The current EpSSG overarching study for children and adults with frontline and relapsed rhabdomyosarcoma (FaR-RMS NCT04625907) includes FOXO1 fusion gene status in place of histology as a risk factor. Additional molecular features of significance have recently been recognized, including the MYOD1L122R gene mutation. Here, we review biological information showing that MYOD1L122R blocks cell differentiation and has a MYC-like activity that enhances tumorigenesis and is linked to an aggressive cellular phenotype. MYOD1L122R mutations can be found together with mutations in other genes, such as PIK3CA, as potentially cooperating events. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ten publications in the clinical literature involving 72 cases were reviewed. MYOD1L122R mutation in RMS can occur in both adults and children and is frequent in sclerosing/spindle cell histology, although it is also significantly reported in a subset of embryonal RMS. MYOD1L122R mutated tumors most frequently arise in the head and neck and extremities and are associated with poor outcome, raising the issue of how to use MYOD1L122R in risk stratification and how to treat these patients most effectively.
Correlation between Imaging Markers Derived from PET/MRI and Invasive Acquired Biomarkers in Newly Diagnosed Breast Cancer
Authors: Jannusch Kai , Bittner Ann-Kathrin , Bruckmann Nils Martin , Morawitz Janna , Stieglitz Cleo , Dietzel Frederic , Quick Harald H. , Baba Hideo A. , Herrmann Ken , Umutlu Lale , Antoch Gerald , Kirchner Julian , Kasimir-Bauer Sabine , Hoffmann Oliver
Published: March 2023

Purpose: Evaluate the diagnostic potential of [18F]FDG-PET/MRI data compared with invasive acquired biomarkers in newly diagnosed early breast cancer (BC). Methods: Altogether 169 women with newly diagnosed BC were included. All underwent a breast- and whole-body [18F]FDG-PET/MRI for initial staging. A tumor-adapted volume of interest was placed in the primaries and defined bone regions on each standard uptake value (SUV)/apparent diffusion coefficient (ADC) dataset. Immunohistochemical markers, molecular subtype, tumor grading, and disseminated tumor cells (DTCs) of each patient were assessed after ultrasound-guided biopsy of the primaries and bone marrow (BM) aspiration. Correlation analysis and group comparisons were assessed. Results: A significant inverse correlation of estrogen-receptor (ER) expression and progesterone-receptor (PR) expression towards SUVmax was found (ER: r = 0.27, p < 0.01; PR: r = 0.19, p < 0.05). HER2-receptor expression showed no significant correlation towards SUV and ADC values. A significant positive correlation between Ki67 and SUVmax and SUVmean (r = 0.42 p < 0.01; r = 0.19 p < 0.05) was shown. Tumor grading significantly correlated with SUVmax and SUVmean (ρ = 0.36 and ρ = 0.39, both p’s < 0.01). There were no group differences between SUV/ADC values of DTC-positive/-negative patients. Conclusions: [18F]FDG-PET/MRI may give a first impression of BC-receptor status and BC-tumor biology during initial staging by measuring glucose metabolism but cannot distinguish between DTC-positive/-negative patients and replace biopsy.
Progress toward Better Treatment of Therapy-Related AML
Authors: Kotsiafti Angeliki , Giannakas Konstantinos , Christoforou Panagiotis , Liapis Konstantinos
Published: March 2023

Therapy-related acute myeloid leukemia (t-AML) comprises 10–20% of all newly diagnosed cases of AML and is related to previous use of chemotherapy or ionizing radiotherapy for an unrelated malignant non-myeloid disorder or autoimmune disease. Classic examples include alkylating agents and topoisomerase II inhibitors, whereas newer targeted therapies such as poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitors have emerged as causative agents. Typically, t-AML is characterized by adverse karyotypic abnormalities and molecular lesions that confer a poor prognosis. Nevertheless, there are also cases of t-AML without poor-risk features. The management of these patients remains controversial. We describe the causes and pathophysiology of t-AML, putting emphasis on its mutational heterogeneity, and present recent advances in its treatment including CPX-351, hypomethylating agent plus venetoclax combination, and novel, molecularly targeted agents that promise to improve the cure rates. Evidence supporting personalized medicine for patients with t-AML is presented, as well as the authors’ clinical recommendations.
Prognostic Value of Simple Non-Invasive Tests for the Risk Stratification of Incident Hepatocellular Carcinoma in Cirrhotic Individuals with Non-Alcoholic Fatty Liver Disease
Authors: Armandi Angelo , Caviglia Gian Paolo , Abdulle Amina , Rosso Chiara , Gjini Kamela , Castelnuovo Gabriele , Guariglia Marta , Perez Diaz del Campo Nuria , D’Amato Daphne , Ribaldone Davide Giuseppe , Saracco Giorgio Maria , Bugianesi Elisabetta
Published: March 2023

Hepatocellular carcinoma (HCC) represents a relevant disease burden in cirrhotic patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the prognostic value of simple non-invasive tests (NITs) (AAR, APRI, BARD, FIB-4) for the stratification of HCC risk development in a cohort of 122 consecutive cirrhotic individuals with NAFLD. Over a median follow up of 5.9 (3.2–9.3) years, 13 (10.7%) developed HCC. Only FIB-4 was associated with HCC risk (HR = 1.27, 95% CI 1.03–1.58, p = 0.027). After evaluating different established FIB-4 cut-offs, the lowest cut-off of 1.45 allowed the ruling out of a greater number of patients with a minimal risk of HCC than the 1.3 cut-off (23 vs. 18 patients). Conversely, the cumulative incidence of HCC using the highest cut-off of 3.25 (rule in) was distinctly higher than the 2.67 cut-off (19.4% vs. 13.3%). After multivariate Cox regression analysis, these cut-offs were independently associated with HCC after adjusting for sex, BMI and T2DM (HR = 6.40, 95% CI 1.71–24.00, p = 0.006). In conclusion, FIB-4 values of <1.3 and >3.25 could allow for the optimal stratification of long-term HCC risk in cirrhotic individuals with NAFLD.
Differential Occupancy and Regulatory Interactions of KDM6A in Bladder Cell Lines
Authors: Özden-Yılmaz Gülden , Savas Busra , Bursalı Ahmet , Eray Aleyna , Arıbaş Alirıza , Senturk Serif , Karaca Ezgi , Karakülah Gökhan , Erkek-Ozhan Serap
Published: March 2023

Epigenetic deregulation is a critical theme which needs further investigation in bladder cancer research. One of the most highly mutated genes in bladder cancer is KDM6A, which functions as an H3K27 demethylase and is one of the MLL3/4 complexes. To decipher the role of KDM6A in normal versus tumor settings, we identified the genomic landscape of KDM6A in normal, immortalized, and cancerous bladder cells. Our results showed differential KDM6A occupancy in the genes involved in cell differentiation, chromatin organization, and Notch signaling depending on the cell type and the mutation status of KDM6A. Transcription factor motif analysis revealed HES1 to be enriched at KDM6A peaks identified in the T24 bladder cancer cell line; moreover, it has a truncating mutation in KDM6A and lacks a demethylase domain. Our co-immunoprecipitation experiments revealed TLE co-repressors and HES1 as potential truncated and wild-type KDM6A interactors. With the aid of structural modeling, we explored how truncated KDM6A could interact with TLE and HES1, as well as RUNX and HHEX transcription factors. These structures provide a solid means of studying the functions of KDM6A independently of its demethylase activity. Collectively, our work provides important contributions to the understanding of KDM6A malfunction in bladder cancer.
Contribution to the Understanding of Mural Painting Techniques of Jinpari Tomb No. 4 of the Complex of Koguryo Tombs, World Heritage
Authors: Lee Hwa Soo , Han Kyeong Soon
Published: March 2023

In this study, we have analyzed the chemical components and crystal structures of minerals found in the Jinpari Tomb No. 4 mural paintings, which has allowed us to identify component materials comprising each layer. During the analysis of the painting layer, the green material was identified as malachite. The use of malachite is supported by the high Cu content, the flower-shaped crystals in the microstructures of the painting layer, and the XRD identification results. The ground layer consists of layers of panel-shaped particles. The main component materials were Ca, Al, Si, K, Mg, and Fe, which are usually found in earthen materials. The earthen layer showed high peaks of silicon oxide and calcium carbonate, along with potassium aluminum silicate. The findings indicate quartz, limestone, and mica. The lime layer showed the diffraction patterns corresponding to calcium carbonate, which indicates the use of limestone. The earthen layer consists of aggregated layers of thin panel-shaped structures, with small particles attached around the structures. The lime layer showed aggregations of multi-angle panel-shaped structures and pillar-shaped structures of various types. The analysis has allowed us to shed light on the techniques used in the Jinpari Tomb No. 4 mural paintings.