bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Changes of Fermentation Metabolites and the Protective Effect of Fermented Edible Grass on Stress Injury Induced by Acetaminophen in HepG2 Cells
Authors: He Tao , Li Xianxiu , Wang Zhenzhen , Mao Jianwei , Mao Yangchen , Sha Ruyi
Published: February 2024

In this study, gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics was used to describe the changes of metabolites in edible grass with Lactobacillus plantarum (Lp) fermentation durations of 0 and 7 days, and subsequently to investigate the protective effect of fermented edible grass on acetaminophen-induced stress injury in HepG2 cells. Results showed that 53 differential metabolites were identified, including 31 significantly increased and 22 significantly decreased metabolites in fermented edible grass. Fermented edible grass protected HepG2 cells against acetaminophen-induced stress injury, which profited from the reduction in lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and the enhancement in superoxide dismutase (SOD) activity. Cell metabolomics analysis revealed that a total of 13 intracellular and 20 extracellular differential metabolites were detected. Fermented edible grass could regulate multiple cell metabolic pathways to exhibit protective effects on HepG2 cells. These findings provided theoretical guidance for the formation and regulation of bioactive metabolites in fermented edible grass and preliminarily confirmed the protective effects of fermented edible grass on drug-induced liver damage.
Predictors of Deterioration in Mental Well-Being and Quality of Life among Family Caregivers and Older People with Long-Term Care Needs during the COVID-19 Pandemic
Authors: Fabbietti Paolo , Santini Sara , Piccinini Flavia , Giammarchi Cinzia , Lamura Giovanni
Published: February 2024

Background: During the COVID-19 pandemic, reduced access to care services and fear of infection prompted families to increase home care for their older relatives with long-term care needs. This had negative effects on both members of the caring dyad, impacting their quality of life (QoL) and mental well-being. This study investigated the factors that influenced the mental well-being and QoL of 239 dyads, before and after the first pandemic wave in Italy. Methods: Data were collected through a survey on the use of health and social care services and interventions by older care recipients living in the community and their family caregivers. Factors associated with deterioration of mental well-being and QoL in older care recipients (mean age 86.1 years old) and their family caregivers after the pandemic were studied. Results: The importance attached by family caregivers to the skills and training of healthcare professionals was a protective factor against the deterioration in the well-being of older care recipients. Similarly, the importance associated by family caregivers to the help received from healthcare professionals was a protective factor for QoL. Financial hardship of older care recipients was a risk factor for deterioration in caregivers’ mental well-being, while support from other family members was a protective factor for QoL. Conclusions: The presence of attentive healthcare professionals, a supportive family environment, and economic support can reduce the burden on both the caregiver and the older care recipient. These aspects need to be considered in any future emergency situation and when planning care services for community-dwelling older people.
Keratin Expression in Podocytopathies, ANCA-Associated Vasculitis and IgA Nephropathy
Authors: Pavlakou Paraskevi , Gakiopoulou Harikleia , Djudjaj Sonja , Palamaris Kostas , Trivyza Maria Stella , Stylianou Kostas , Goumenos Dimitrios S. , Papachristou Evangelos , Papasotiriou Marios
Published: February 2024

Keratins are the main components of the cell cytoskeleton of epithelial cells. Epithelial cells under stressful stimuli react by modifying their keratin expression pattern. Glomerular diseases are pathological conditions that may lead to loss of kidney function if not timely diagnosed and treated properly. This study aims to examine glomerular and tubular keratin expression in podocytopathies, ANCA-associated vasculitis, and IgA nephropathy and how this expression correlates to clinical outcomes. We included 45 patients with podocytopathies (minimal change disease and focal segmental glomerulosclerosis), ANCA-associated vasculitis, and IgA nephropathy, with or without crescentic lesions, and healthy controls. All tissues were assessed by photon microscopy and immunohistochemistry. Biopsy sections were examined for keratins 7, 8, 18, and 19 expression in the glomerular and tubulointerstitial areas separately. Moreover, we examined how keratin expression was correlated with long-term kidney function outcomes. All four studied keratins had significantly increased glomerular expression in patients with ANCA vasculitis compared to controls and MCD patients. Tubular expression of keratins 7, 8, and 19 was related to kidney outcome in all groups. Patients with crescents had higher expression of all keratins in both glomeruli and tubulointerstitium. The presence of tubular atrophy, interstitial fibrosis, mesangial hyperplasia, and interstitial inflammation did not affect keratin expression. Keratins, an abundant component of renal epithelial cells, have the potential to be featured as a biomarker for kidney function prognosis in patients with glomerular diseases.
Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer
Authors: Tien Amy H. , Sadar Marianne D.
Published: February 2024

Breast cancer is a major cause of death worldwide. The complexity of endocrine regulation in breast cancer may allow the cancer cells to escape from a particular treatment and result in resistant and aggressive disease. These breast cancers usually have fewer treatment options. Targeted therapies for cancer patients may offer fewer adverse side effects because of specificity compared to conventional chemotherapy. Signaling pathways of nuclear receptors, such as the estrogen receptor (ER), have been intensively studied and used as therapeutic targets. Recently, the role of the androgen receptor (AR) in breast cancer is gaining greater attention as a therapeutic target and as a prognostic biomarker. The expression of constitutively active truncated AR splice variants in breast cancer is a possible mechanism contributing to treatment resistance. Therefore, targeting both the full-length AR and AR variants, either through the activation or suppression of AR function, depending on the status of the ER, progesterone receptor, or human epidermal growth factor receptor 2, may provide additional treatment options. Studies targeting AR in combination with other treatment strategies are ongoing in clinical trials. The determination of the status of nuclear receptors to classify and identify patient subgroups will facilitate optimized and targeted combination therapies.
Production of Bioactive Porcine Lactoferrin through a Novel Glucose-Inducible Expression System in Pichia pastoris: Unveiling Antimicrobial and Anticancer Functionalities
Authors: Yen Chih-Ching , Wu Pei-Ying , Ou-Yang Huan , Chen Hsiao-Ling , Chong Kowit-Yu , Chang Ro-Lin , Chen Chuan-Mu
Published: February 2024

Lactoferrin (LF) stands as one of the extensively investigated iron-binding glycoproteins within milk, exhibiting diverse biological functionalities. The global demand for LF has experienced consistent growth. Biotechnological strategies aimed at enhancing LF productivity through microbial expression systems offer substantial cost-effective advantages and exhibit fewer constraints compared to traditional animal bioreactor technologies. This study devised a novel recombinant plasmid, wherein the AOX1 promoter was replaced with a glucose-inducible G1 promoter (PG1) to govern the expression of recombinant porcine LF (rpLF) in Pichia pastoris GS115. High-copy-number PG1-rpLF yeast clones were meticulously selected, and subsequent induction with 0.05 g/L glucose demonstrated robust secretion of rpLF. Scaling up production transpired in a 5 L fermenter, yielding an estimated rpLF productivity of approximately 2.8 g/L by the conclusion of glycerol-fed fermentation. A three-step purification process involving tangential-flow ultrafiltration yielded approximately 6.55 g of rpLF crude (approximately 85% purity). Notably, exceptional purity of rpLF was achieved through sequential heparin and size-exclusion column purification. Comparatively, the present glucose-inducible system outperformed our previous methanol-induced system, which yielded a level of 87 mg/L of extracellular rpLF secretion. Furthermore, yeast-produced rpLF demonstrated affinity for ferric ions (Fe3+) and exhibited growth inhibition against various pathogenic microbes (E. coli, S. aureus, and C. albicans) and human cancer cells (A549, MDA-MB-231, and Hep3B), similar to commercial bovine LF (bLF). Intriguingly, the hydrolysate of rpLF (rpLFH) manifested heightened antimicrobial and anticancer effects compared to its intact form. In conclusion, this study presents an efficient glucose-inducible yeast expression system for large-scale production and purification of active rpLF protein with the potential for veterinary or medical applications.
Primary Electrical Heart Disease—Principles of Pathophysiology and Genetics
Authors: Badura Krzysztof , Buławska Dominika , Dąbek Bartłomiej , Witkowska Alicja , Lisińska Wiktoria , Radzioch Ewa , Skwira Sylwia , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: February 2024

Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.
Copper(II)-Assisted Degradation of Pheophytin a by Reactive Oxygen Species
Authors: Orzeł Łukasz , Drzewiecka-Matuszek Agnieszka , Rutkowska-Zbik Dorota , Krasowska Aneta , Fiedor Leszek , van Eldik Rudi , Stochel Grażyna
Published: February 2024

The central ion Mg2+ is responsible for the differences between chlorophyll a and its free base in their reactivity toward metal ions and thus their resistance to oxidation. We present here the results of spectroscopic (electronic absorption and emission, circular dichroism, and electron paramagnetic resonance), spectroelectrochemical, and computational (based on density functional theory) investigations into the mechanism of pheophytin, a degradation that occurs in the presence of Cu ions and O2. The processes leading to the formation of the linear form of tetrapyrrole are very complex and involve the weakening of the methine bridge due to an electron withdrawal by Cu(II) and the activation of O2, which provides protection to the free ends of the opening macrocycle. These mechanistic insights are related to the naturally occurring damage to the photosynthetic apparatus of plants growing on metal-contaminated soils.
Repeat Coronary Angiography in Patients Aged over 50 Years with Previously Normal/Non-Obstructive Coronary Angiogram—Insights from a Retrospective Study
Authors: Roguin Ariel , Kobo Ofer , Meisel Simha-Ron , Darawsha Ziad , Odeh Mahmood , Frimerman Aharon , Amsalem Naama , Abu Fanne Rami
Published: February 2024

(1) Introduction: A significant proportion of patients undergoing coronary angiography (CAG) have normal (NCA) or non-obstructive coronary artery disease (NOCAD). This study retrospectively tested the incidence of re-catheterization, and long-term outcomes of this population in patients aged over 50 years. (2) Methods: We identified all patients above 50 years of age with NOCAD who underwent their first CAG at our center between January 2008 and December 2019. Patients were evaluated for their baseline characteristics, risk factors profile, and indication for CAG. Patients undergoing repeat CAG after the index procedure were assessed for the above, including the primary preventive pharmacotherapy prescribed. (3) Results: A total of 1939 patients were reported to have NOCAD. Of these, 1756 (90%) patients (62% males, median age 66 (56–75) years) had no repeat angiography (group 1). Repeat angiography was performed in 10%: 136 (7%) proved futile (median time for repeat angiography 5 (3–8) years) (group 3), and 47 (3%) ended with angioplasty (median time for repeat angiography 4 (3–6) years) (group 2). Male gender, BMI above 30 (23% vs. 13%), hypertension (68% vs. 57%), diabetes (28% vs. 17%) and smoking (36% vs. 19%) were significantly higher in the interventional group. Regression analysis showed both paroxysmal atrial fibrillation and hyperlipidemia were significantly associated with repeat CAG. The indication for the first CAG was mainly symptoms related. In the interventional repeat angiography (n = 47) the incidence of troponin positive cases increased from 8.2% before intervention to 57.5%, 50% being ST elevation cases. The symptoms-related cases went from 36.7% to 18.4%. Intriguingly, 85% of the interventional group were not prescribed statin and/or aspirin on a regular basis, and/or did not adhere to treatment. (4) Conclusions: NOCAD is a frequent occurrence. The threshold for repeat angiography must be higher, better reserved to troponin positive cases. Moreover, patients must be handled according to their risk profile, not being mistakenly reassured by a snapshot benign coronary angiography.
Dopamine Synthesis in the Nigrostriatal Dopaminergic System in Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage
Authors: Blokhin Victor , Pavlova Ekaterina N. , Katunina Elena A. , Nodel Marina R. , Kataeva Galina V. , Moskalets Elina R. , Pronina Tatiana S. , Ugrumov Michael V.
Published: February 2024

Parkinson’s disease (PD) is diagnosed by the onset of motor symptoms and treated long after its onset. Therefore, the development of the early diagnosis of PD is a priority for neurology. Advanced methodologies for this include (1) searching for patients at risk of developing prodromal PD based on premotor symptoms; (2) searching for changes in the body fluids in these patients as diagnostic biomarkers; (3) verifying the diagnosis of prodromal PD and diagnostic-value biomarkers using positron emission tomography (PET); (4) anticipating the development of motor symptoms. According to our data, the majority of patients (n = 14) at risk of developing PD selected in our previous study show pronounced interhemispheric asymmetry in the incorporation of 18F-DOPA into dopamine synthesis in the striatum. This was assessed for the caudate nucleus and putamen separately using the specific binding coefficient, asymmetry index, and putamen/caudate nucleus ratio. Interhemispheric asymmetry in the incorporation of 18F-DOPA into the striatum provides strong evidence for its dopaminergic denervation and the diagnostic value of previously identified blood biomarkers. Of the 17 patients at risk of developing prodromal PD studied using PET, 3 patients developed motor symptoms within a year. Thus, our study shows the promise of using the described methodology for the development of early diagnosis of PD.
Improvement of Machine Learning-Based Modelling of Container Ship’s Main Particulars with Synthetic Data
Authors: Majnarić Darin , Baressi Šegota Sandi , Anđelić Nikola , Andrić Jerolim
Published: February 2024

One of the main problems in the application of machine learning techniques is the need for large amounts of data necessary to obtain a well-generalizing model. This is exacerbated for studies in which it is not possible to access large amounts of data—for example, in the case of ship main data modelling, where a limited amount of real-world data (ship main data) is available for dataset creation. In this paper, a synthetic data generation technique has been applied to generate a large amount of synthetic data points regarding container ships’ main particulars. Models are trained using a multilayer perceptron (MLP) regressor on both original and synthetic data mixed with original data points. Then, the authors validate the performance of the obtained models on the original data and conclude whether a synthetic-data-based approach can be used to develop models in instances where the amount of data on ship main particulars may be limited. The results demonstrate an improvement across almost all outputs, ranging between 0.01 and 0.21 when evaluated using the coefficient of determination (R2) and between 0.27% and 3.43% when models are evaluated with mean absolute percentage error (MAPE). This indicates that the application of synthetic data can indeed be used for the improvement of ML-based model performance. The presented study demonstrates that the application of ML-based syncretization techniques can provide significant improvements to the process of ML-based determination of a ship’s main particulars at the early design stage. This paper suggests that, in cases where only a small dataset is available, artificial neural networks (ANN) can still be effectively employed to derive early-stage design values for the main particulars through the use of synthetic data.
Effect of Rockfall Spatial Representation on the Accuracy and Reliability of Susceptibility Models (The Case of the Haouz Dorsale Calcaire, Morocco)
Authors: El Miloudi Youssef , El Kharim Younes , Bounab Ali , El Hamdouni Rachid
Published: February 2024

Rockfalls can cause loss of life and material damage. In Northern Morocco, rockfalls and rock avalanche-deposits are frequent, especially in the Dorsale Calcaire morpho-structural unit, which is mostly formed by Jurassic limestone and dolostone formations. In this study, we focus exclusively on its northern segment, conventionally known as “the Haouz subunit”. First, a rockfall inventory was conducted. Then, two datasets were prepared: one covering exclusively the source area and the other representing the entirety of the mass movements (source + propagation area). Two algorithms were then used to build rockfall susceptibility models (RSMs). The first one (Logistic Regression: LR) yielded the most unreliable results, where the RSM derived from the source area dataset significantly outperformed the one based on the entirety of the rockfall affected area, despite the lack of significant visual differences between both models. However, the RSMs produced using Artificial Neural Networks (ANNs) were more or less similar in terms of accuracy, despite the source area model being more conservative. This result is unexpected given the fact that previous studies proved the robustness of the LR algorithm and the sensitivity of ANN models. However, we believe that the non-linear correlation between the spatial distribution of the rockfall propagation area and that of the conditioning factors used to compute the models explains why modeling rockfalls in particular differs from other types of landslides.
Assessing Long-Term Thermal Environment Change with Landsat Time-Series Data in a Rapidly Urbanizing City in China
Authors: Huang Conghong , Tang Yan , Wu Yiyang , Tao Yu , Xu Muwu , Xu Nan , Li Mingze , Liu Xiaodan , Xi Henghui , Ou Weixin
Published: February 2024

The studies of urban heat islands or urban thermal environments have attracted extensive attention, although there is still a lack of research focused on the analysis of long-term urban thermal environment change with fine spatial resolution and actual exposure of urban residents. Taking the rapidly urbanizing city of Nanjing, China as an example, this study utilizes the Landsat-derived daytime time-series land surface temperature data to comprehensively assess the city’s long-term (30-year) urban thermal environment change. The results showed that: (1) The overall surface urban heat island intensity showed a noticeable trend of first increasing and then decreasing from 1990 to 2020. (2) It exhibited the detailed spatial distribution of urban heat/cold islands within the urban center boundary. The percentage of surface urban heat islands was 77.01% in 1990, and it increased to 85.79% in 2010 and then decreased to 80.53% in 2020. (3) More than 65% of the urban residents have lived in areas with a surface urban heat island intensity greater than 3.0 °C, which also showed a trend of first increasing and then decreasing from 1990 to 2020. The methods and findings of this study can provide a reference for other studies on urban thermal environment changes and urban sustainable development.
Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma
Authors: Woodhead Gregory , Lee Sean , Struycken Lucas , Goldberg Daniel , Hannallah Jack , Young Shamar
Published: February 2024

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.
Prediction of Hydration Heat for Diverse Cementitious Composites through a Machine Learning-Based Approach
Authors: Lu Liqun , Li Yingze , Wang Yuncheng , Wang Fengjuan , Lu Zeyu , Liu Zhiyong , Jiang Jinyang
Published: February 2024

Hydration plays a crucial role in cement composites, but the traditional methods for measuring hydration heat face several limitations. In this study, we propose a machine learning-based approach to predict hydration heat at specific time points for three types of cement composites: ordinary Portland cement pastes, fly ash cement pastes, and fly ash–metakaolin cement composites. By adjusting the model architecture and analyzing the datasets, we demonstrate that the optimized artificial neural network model not only performs well during the learning process but also accurately predicts hydration heat for various cement composites from an extra dataset. This approach offers a more efficient way to measure hydration heat for cement composites, reducing the need for labor- and time-intensive sample preparation and testing. Furthermore, it opens up possibilities for applying similar machine learning approaches to predict other properties of cement composites, contributing to efficient cement research and production.
Catheter Ablation of Atrial Tachycardia after Pulmonary Vein Isolation in a Patient with Common Ostium of Inferior Pulmonary Veins: Case Report
Authors: Babic Milos , Djurdjevic Branko , Vukajlovic Dejan , Jovicic Mihailo , Petrovic Masa , Kljajevic Jelena , Tomovic Milosav , Nikolic Aleksandra
Published: February 2024

Background and Objectives: Atrial fibrillation (AF), a prevalent cardiac arrhythmia, significantly impacts the quality of life of those affected. The preferred treatment for symptomatic AF, particularly when pharmacological methods fall short, is catheter ablation with pulmonary vein isolation (PVI). While common pulmonary vein (PV) anatomical variants, such as the right accessory pulmonary vein and the common ostium of left pulmonary veins (LCPV), have been studied extensively, their impact on the long-term outcome of PVI is known to be minimal. However, data on less common anomalies, like the common ostium of the left and right inferior pulmonary vein (CIPV), remain scarce in the medical literature. This report aims to shed light on the challenges and outcomes of catheter ablation in a patient with a rare CIPV anomaly. By presenting this case, we contribute to the limited knowledge about the management of such unique anatomical variations in AF treatment and discuss the importance of individualized treatment approaches. Case Presentation: We present a case involving a 56-year-old male diagnosed with AF in 2018. Initial PVI treatment was successful, but the patient experienced symptom recurrence after three years. A preprocedural CT scan before the second ablation revealed a CIPV anomaly. During the repeat procedure, a right superior pulmonary vein (RSPV) reisolation was performed due to identified gaps in the previous ablation line. Post-procedure, the patient maintained a sinus rhythm and reported no further symptoms. Conclusions: This case highlights the importance of recognizing rare PV anatomies like CIPV in the effective management of AF. Tailored ablation strategies, accounting for unique anatomical conditions, can lead to successful long-term outcomes, reinforcing the need for personalized approaches in AF treatment, especially in cases involving complex anatomical variations.
Neuroprotection of Truncated Peptide IIAVE from Isochrysis zhanjiangensis: Quantum Chemical, Molecular Docking, and Bioactivity Studies
Authors: Liu Qiuqi , Lin Liyuan , Li Huijuan , Qian Zhong-Ji
Published: February 2024

Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile–Ile–Ala–Val–Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight. The structure and antioxidant activity of IIAVE were tested in a previous study and proved to have good antioxidant potential. In this study, the chemical properties of IIAVE were calculated using quantum chemical methods, including frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural population analysis (NPA), and global reactivity properties. The interaction of IIAVE with Bcl-2 and DJ-1 was investigated using the molecular docking method. The results showed that IIAVE promoted the activation of the Keap1/Nrf2 pathway and up-regulated the expression of the superoxide dismutase 1 (SOD-1) protein by inhibiting the level of reactive oxygen species (ROS) in cells. In addition, IIAVE inhibits ROS production and prevents 6-OHDA-induced oxidative damage by restoring mitochondrial membrane potential. Furthermore, IIAVE inhibited cell apoptosis by increasing the Bcl-2/Bax ratio and inhibiting the activation of Caspase-9 and Caspase-3. Thus, IIAVE may become a potential drug for the treatment and prevention of PD.
Application of Weighted Gene Co-Expression Network Analysis to Metabolomic Data from an ApoA-I Knockout Mouse Model
Authors: Zhou Zhe , Liu Jiao , Liu Jia
Published: February 2024

As the ability to collect profiling data in metabolomics increases substantially with the advances in Liquid Chromatography–Mass Spectrometry (LC-MS) instruments, it is urgent to develop new and powerful data analysis approaches to match the big data collected and to extract as much meaningful information as possible from tens of thousands of molecular features. Here, we applied weighted gene co-expression network analysis (WGCNA), an algorithm popularly used in microarray or RNA sequencing, to plasma metabolomic data and demonstrated several advantages of WGCNA over conventional statistical approaches such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). By using WGCNA, a large number of molecular features were clustered into a few modules to reduce the dimension of a dataset, the impact of phenotypic traits such as diet type and genotype on the plasma metabolome was evaluated quantitatively, and hub metabolites were found based on the network graph. Our work revealed that WGCNA is a very powerful tool to decipher, interpret, and visualize metabolomic datasets.
Negative Association of Lignan and Phytosterol Intake with Stress Perception during the COVID-19 Pandemic—A Polish Study on Young Adults
Authors: Micek Agnieszka , Jagielski Paweł , Bolesławska Izabela , Witkowska Anna Maria , Waśkiewicz Anna , Wajda Zbigniew , Kamińska Anna , Cebula Aneta , Godos Justyna
Published: February 2024

Background: There has been an increasing global prevalence of depression and other psychiatric diseases in recent years. Perceived stress has been proven to be associated with psychiatric and somatic symptoms. Some animal and human studies have suggested that consuming foods abundant in lignans and phytosterols may be associated with lower levels of stress, depression, and anxiety. Still, the evidence is not yet strong enough to draw firm conclusions. Thus, we investigated the association between dietary intake of these phytochemicals and the level of stress experienced by adult individuals. Methods: Diet was assessed using self-reported 7-day dietary records. The intakes of lignans and phytosterols were estimated using databases with their content in various food products. The Perceived Stress Scale (PSS) was implemented to measure the level of perceived stress. A logistic regression analysis was used to test for associations. Results: The odds of elevated PSS were negatively associated with dietary intake of total phytosterols, stigmasterol, and β-sitosterol, with evidence of a decreasing trend across tertiles of phytochemicals. The analysis for doubling the intake reinforced the aforementioned relationships and found protective effects against PSS for total lignans, pinoresinol, and campesterol. Conclusions: Habitual inclusion of lignans and phytosterols in the diet may play a role in psychological health. To address the global outbreak of depression and other mental health issues triggered by stress, it is important to take a holistic approach. There is a need to develop effective strategies for prevention and treatment, among which certain dietary interventions such as consumption of products abundant in lignans and phytosterols may play a substantial role.
Therapeutic Implications of Ceritinib in Cholangiocarcinoma beyond ALK Expression and Mutation
Authors: Myint Kyaw Zwar , Balasubramanian Brinda , Venkatraman Simran , Phimsen Suchada , Sripramote Supisara , Jantra Jeranan , Choeiphuk Chaiwat , Mingphruedhi Somkit , Muangkaew Paramin , Rungsakulkij Narongsak , Tangtawee Pongsatorn , Suragul Wikran , Farquharson Watoo Vassanasiri , Wongprasert Kanokpan , Chutipongtanate Somchai , Sanvarinda Pimtip , Ponpuak Marisa , Poungvarin Naravat , Janvilisri Tavan , Suthiphongchai Tuangporn , Yacqub-Usman Kiren , Grabowska Anna M. , Bates David O. , Tohtong Rutaiwan
Published: February 2024

Cholangiocarcinoma (CCA) is a difficult-to-treat cancer, with limited therapeutic options and surgery being the only curative treatment. Standard chemotherapy involves gemcitabine-based therapies combined with cisplatin, oxaliplatin, capecitabine, or 5-FU with a dismal prognosis for most patients. Receptor tyrosine kinases (RTKs) are aberrantly expressed in CCAs encompassing potential therapeutic opportunity. Hence, 112 RTK inhibitors were screened in KKU-M213 cells, and ceritinib, an approved targeted therapy for ALK-fusion gene driven cancers, was the most potent candidate. Ceritinib’s cytotoxicity in CCA was assessed using MTT and clonogenic assays, along with immunofluorescence, western blot, and qRT-PCR techniques to analyze gene expression and signaling changes. Furthermore, the drug interaction relationship between ceritinib and cisplatin was determined using a ZIP synergy score. Additionally, spheroid and xenograft models were employed to investigate the efficacy of ceritinib in vivo. Our study revealed that ceritinib effectively killed CCA cells at clinically relevant plasma concentrations, irrespective of ALK expression or mutation status. Ceritinib modulated multiple signaling pathways leading to the inhibition of the PI3K/Akt/mTOR pathway and activated both apoptosis and autophagy. Additionally, ceritinib and cisplatin synergistically reduced CCA cell viability. Our data show ceritinib as an effective treatment of CCA, which could be potentially explored in the other cancer types without ALK mutations.
Optimizing the Extraction Process of Value-Added Products from Olive Cake Using Neuro-Fuzzy Models
Authors: Lozano Emilio J. , Blázquez Gabriel , Calero Mónica , Martín-Lara María Ángeles , Pérez-Huertas Salvador , Pérez Antonio
Published: February 2024

The use of olive cake, an abundant residue in the olive oil industry, has been studied by developing a biorefinery scheme. The aim was to develop a novel, efficient, and environmentally friendly strategy for the valorization of olive cake, contributing to sustainable agriculture. A special extraction procedure based on a combination of hydrothermal treatments with liquid/liquid extractions was designed to produce value-added products, along with solids that can be used for energy or adsorbent production. The optimal extraction conditions were determined by exploring the influence of the operating variables (temperature, extraction time, solvent type, solvent/extract ratio, extraction stages, and pH) on the extraction yield. The decision about the optimal conditions was made by adjusting the experimental results to a neuro-fuzzy model. Glucose and inositol showed similar response surfaces, allowing simultaneous concentration in a single process. Under optimal extraction conditions, the concentration of inositol increased by up to 70%, while glucose and fructose increased by 70 and 30 times, respectively, compared to the initial feed. The proposed methodology successfully extracted significant amounts of bioactive polyols (mainly inositol) (1126 mg/L), saccharides (15,960 mg/L glucose, 385 mg/L xylose, 5550 mg/L fructose, 165 mg/L lactose, and 248 mg/L sucrose), and polyphenols (4792 mg/L) under mild conditions, i.e., 30 °C and 30 min. Thus, olive cake extracts have a great unexploited potential for application in several industrial sectors, including, but not limited to, food and pharmaceuticals.
Preparation of Nickel-Based Bimetallic Catalyst and Its Activation of Persulfate for Degradation of Methyl Orange
Authors: Zhang Bo , Li Jiale , Xu Zhizhi , Xu Xiaohong , Wu Chundu
Published: February 2024

In this research, a new catalyst for activating persulfate was developed by loading iron and nickel ions onto powdered activated carbon (PAC) for treating methyl orange, and the preparation process was optimized and characterized. The efficacy of the treatment was evaluated using the Chemical Oxygen Demand (COD) removal rate, which reflects the impact of various process parameters, including catalyst dosage, sodium persulfate dosage, and reaction pH. Finally, the recovery and reuse performance of the catalyst were studied. The optimal conditions for preparing the activated sodium persulfate catalyst were determined to be as follows: a molar ratio of Fe3+ and Fe2+ to Ni of 4:1, a mass ratio of Fe3O4 to PAC of 1:4, a calcination temperature of 700 °C, and a calcination time of 4 h. This preparation led to an increase in surface porosity and the formation of a hollow structure within the catalyst. The active material on the surface was identified as nickel ferrite, comprising the elements C, O, Fe, and Ni. The magnetic property is beneficial to recycling. With the increase in catalyst and sodium persulfate dosage, the COD removal efficiency of the oxidation system increased first, and then, decreased. The catalyst showed good catalytic performance when the pH value was in the range of 3~11. Furthermore, Gas Chromatography–Mass Spectrometry (GC-MS) analysis indicated the complete oxidation of methyl orange dye molecules in the system. This result highlights the important role of the newly developed catalyst in activating persulfate.
Resilient Multi-Sensor UAV Navigation with a Hybrid Federated Fusion Architecture
Authors: Negru Sorin Andrei , Geragersian Patrick , Petrunin Ivan , Guo Weisi
Published: February 2024

Future UAV (unmanned aerial vehicle) operations in urban environments demand a PNT (position, navigation, and timing) solution that is both robust and resilient. While a GNSS (global navigation satellite system) can provide an accurate position under open-sky assumptions, the complexity of urban operations leads to NLOS (non-line-of-sight) and multipath effects, which in turn impact the accuracy of the PNT data. A key research question within the research community pertains to determining the appropriate hybrid fusion architecture that can ensure the resilience and continuity of UAV operations in urban environments, minimizing significant degradations of PNT data. In this context, we present a novel federated fusion architecture that integrates data from the GNSS, the IMU (inertial measurement unit), a monocular camera, and a barometer to cope with the GNSS multipath and positioning performance degradation. Within the federated fusion architecture, local filters are implemented using EKFs (extended Kalman filters), while a master filter is used in the form of a GRU (gated recurrent unit) block. Data collection is performed by setting up a virtual environment in AirSim for the visual odometry aid and barometer data, while Spirent GSS7000 hardware is used to collect the GNSS and IMU data. The hybrid fusion architecture is compared to a classic federated architecture (formed only by EKFs) and tested under different light and weather conditions to assess its resilience, including multipath and GNSS outages. The proposed solution demonstrates improved resilience and robustness in a range of degraded conditions while maintaining a good level of positioning performance with a 95th percentile error of 0.54 m for the square scenario and 1.72 m for the survey scenario.
Detection of Malicious Threats Exploiting Clock-Gating Hardware Using Machine Learning
Authors: Kose Nuri Alperen , Jinad Razaq , Rasheed Amar , Shashidhar Narasimha , Baza Mohamed , Alshahrani Hani
Published: February 2024

Embedded system technologies are increasingly being incorporated into manufacturing, smart grid, industrial control systems, and transportation systems. However, the vast majority of today’s embedded platforms lack the support of built-in security features which makes such systems highly vulnerable to a wide range of cyber-attacks. Specifically, they are vulnerable to malware injection code that targets the power distribution system of an ARM Cortex-M-based microcontroller chipset (ARM, Cambridge, UK). Through hardware exploitation of the clock-gating distribution system, an attacker is capable of disabling/activating various subsystems on the chip, compromising the reliability of the system during normal operation. This paper proposes the development of an Intrusion Detection System (IDS) capable of detecting clock-gating malware deployed on ARM Cortex-M-based embedded systems. To enhance the robustness and effectiveness of our approach, we fully implemented, tested, and compared six IDSs, each employing different methodologies. These include IDSs based on K-Nearest Classifier, Random Forest, Logistic Regression, Decision Tree, Naive Bayes, and Stochastic Gradient Descent. Each of these IDSs was designed to identify and categorize various variants of clock-gating malware deployed on the system. We have analyzed the performance of these IDSs in terms of detection accuracy against various types of clock-gating malware injection code. Power consumption data collected from the chipset during normal operation and malware code injection attacks were used for models’ training and validation. Our simulation results showed that the proposed IDSs, particularly those based on K-Nearest Classifier and Logistic Regression, were capable of achieving high detection rates, with some reaching a detection rate of 0.99. These results underscore the effectiveness of our IDSs in protecting ARM Cortex-M-based embedded systems against clock-gating malware.
Research on Multi-Hole Localization Tracking Based on a Combination of Machine Vision and Deep Learning
Authors: Hou Rong , Yin Jianping , Liu Yanchen , Lu Huijuan
Published: February 2024

In the process of industrial production, manual assembly of workpieces exists with low efficiency and high intensity, and some of the assembly process of the human body has a certain degree of danger. At the same time, traditional machine learning algorithms are difficult to adapt to the complexity of the current industrial field environment; the change in the environment will greatly affect the accuracy of the robot’s work. Therefore, this paper proposes a method based on the combination of machine vision and the YOLOv5 deep learning model to obtain the disk porous localization information, after coordinate mapping by the ROS communication control robotic arm work, in order to improve the anti-interference ability of the environment and work efficiency but also reduce the danger to the human body. The system utilizes a camera to collect real-time images of targets in complex environments and, then, trains and processes them for recognition such that coordinate localization information can be obtained. This information is converted into coordinates under the robot coordinate system through hand–eye calibration, and the robot is then controlled to complete multi-hole localization and tracking by means of communication between the upper and lower computers. The results show that there is a high accuracy in the training and testing of the target object, and the control accuracy of the robotic arm is also relatively high. The method has strong anti-interference to the complex environment of industry and exhibits a certain feasibility and effectiveness. It lays a foundation for achieving the automated installation of docking disk workpieces in industrial production and also provides a more favorable choice for the production and installation of the process of screw positioning needs.
Fear of Missing Out: Constrained Trial of Blockchain in Supply Chain
Authors: Kromes Roland , Li Tianyu , Bouillon Maxime , Güler Talha , van der Hulst Victor , Erkin Zekeriya
Published: February 2024

Blockchain’s potential to revolutionize supply chain and logistics with transparency and equitable stakeholder engagement is significant. However, challenges like scalability, privacy, and interoperability persist. This study explores the scarcity of real-world blockchain implementations in supply chain and logistics since we have not witnessed many real-world deployments of blockchain-based solutions in the field. Puzzled by this, we integrate technology, user experience, and operational efficiency to illuminate the complex landscape of blockchain integration. We present blockchain-based solutions in three use cases, comparing them with alternative designs and analyzing them in terms of technical, economic, and operational aspects. Insights from a tailored questionnaire of 50 questions addressed to practitioners and experts offer crucial perspectives on blockchain adoption. One of the key findings from our work shows that half of the companies interviewed agree that they will miss the potential for competitive advantage if they do not invest in blockchain technology, and 61% of the companies surveyed claimed that their customers ask for more transparency in supply chain-related transactions. However, only one-third of the companies were aware of the main features of blockchain technology, which shows a lack of knowledge among the companies that may lead to a weaker blockchain adaption in supply chain use cases. Our readers should note that our study is specifically contextualized in a Netherlands-funded national project. We hope that researchers as well as stakeholders in supply chain and logistics can benefit from the insights of our work.
The Impact of an Outdoor Motor–Cognitive Exercise Programme on the Health Outcomes of Older Adults in Community Settings: A Pilot and Feasibility Study
Authors: Zwingmann Katharina , Schlesinger Torsten , Müller Katrin
Published: February 2024

Physical and cognitive exercises can prevent or at least mitigate the symptoms of certain diseases and help older adults perform a range of daily functions. Yet, most seniors do not meet the World Health Organisation’s recommended guidelines for physical activity. The objective of this study is to promote and maintain the physical and cognitive capacity of older adults by implementing a feasible and effective low-threshold, age-appropriate, motor–cognitive training outdoors. In the German city of Chemnitz, citizens aged 60 years and older participated in a quasi-randomised intervention trial. Exercises to train coordination, strength, endurance, and cognition were integrated into a 12-week outdoor motor–cognitive exercise programme. Both the physical (e.g., 6MWT) and cognitive skills (e.g., TMT B) of the intervention group (n = 41) and control group (no intervention, n = 58) were measured before (T1) and after (T2) completion of the exercise programme. Some of the participants’ physical and all their cognitive measures improved. Neurocognitive performance (DSST) showed a significant time × group interaction effect (F(1,95) = 6.943, p = 0.010, ηp2 = 0.068). Sex and age were found to be influencing factors. We consider our exercise programme to be successfully implemented, well received by the participants, and feasible and useful to promote the continued exercise of daily functions as part of healthy aging in community-dwelling older adults.