bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Kidney Injury Induces Oxidative Stress and Hepatic Lipid Accumulation through AMPK Signaling Pathway
Authors: Au-Yeung Kathy K. W. , Shang Yue , Wijerathne Charith U. B. , Madduma Hewage Susara , Siow Yaw L. , O Karmin
Published: April 2023

Acute kidney injury (AKI) often impairs the function of other organs leading to distant organ injury. The liver is the major organ that regulates metabolism and lipid homeostasis in the body. It has been reported that AKI causes liver injury with increased oxidative stress, inflammatory response and steatosis. In the present study, we investigated the mechanisms by which ischemia-reperfusion-induced AKI caused hepatic lipid accumulation. Kidney ischemia (45 min)-reperfusion (24 h) led to a significant increase in plasma creatinine and transaminase in Sprague Dawley rats, indicating kidney and liver injury. Histological and biochemical analyses revealed hepatic lipid accumulation with a significant elevation of triglyceride and cholesterol levels in the liver. This was accompanied by a decreased AMP-activated protein kinase (AMPK) phosphorylation, indicating the reduced activation of AMPK, which is an energy sensor that regulates lipid metabolism. The expression of AMPK-regulated genes that were responsible for fatty acid oxidation (CPTIα, ACOX) was significantly decreased, while the expression of lipogenesis genes (SREPB-1c, ACC1) was significantly elevated. The oxidative stress biomarker malondialdehyde was elevated in the plasma and liver. Incubation of HepG2 cells with an oxidative stress inducer hydrogen peroxide inhibited AMPK phosphorylation and caused cellular lipid accumulation. This was accompanied by decreased expression of genes responsible for fatty acid oxidation and increased expression of genes responsible for lipogenesis. These results suggest that AKI elicits hepatic lipid accumulation through decreased fatty acid metabolism and increased lipogenesis. Oxidative stress may contribute, in part, to the downregulation of the AMPK signaling pathway leading to hepatic lipid accumulation and injury.
Impact of Elicitation on Plant Antioxidants Production in Taxus Cell Cultures
Authors: Perez-Matas Edgar , Garcia-Perez Pascual , Bonfill Mercedes , Lucini Luigi , Hidalgo-Martinez Diego , Palazon Javier
Published: April 2023

Elicited cell cultures of Taxus spp. are successfully used as sustainable biotechnological production systems of the anticancer drug paclitaxel, but the effect of the induced metabolomic changes on the synthesis of other bioactive compounds by elicitation has been scarcely studied. In this work, a powerful combinatorial approach based on elicitation and untargeted metabolomics was applied to unravel and characterize the effects of the elicitors 1 µM of coronatine (COR) or 150 µM of salicylic acid (SA) on phenolic biosynthesis in Taxus baccata cell suspensions. Differential effects on cell growth and the phenylpropanoid biosynthetic pathway were observed. Untargeted metabolomics analysis revealed a total of 83 phenolic compounds, mainly flavonoids, phenolic acids, lignans, and stilbenes. The application of multivariate statistics identified the metabolite markers attributed to elicitation over time: up to 34 compounds at 8 days, 41 for 16 days, and 36 after 24 days of culture. The most notable metabolic changes in phenolic metabolism occurred after 8 days of COR and 16 days of SA elicitation. Besides demonstrating the significant and differential impact of elicitation treatments on the metabolic fingerprint of T. baccata cell suspensions, the results indicate that Taxus ssp. biofactories may potentially supply not only taxanes but also valuable phenolic antioxidants, in an efficient optimization of resources.
An Integrated Method for the Vibroacoustic Evaluation of a Carbon Fiber Bouzouki
Authors: Brezas Spyros , Katsipis Markos , Orphanos Yannis , Kaselouris Evaggelos , Kechrakos Kostas , Kefaloyannis Nikos , Papadaki Helen , Sarantis-Karamesinis Antonis , Petrakis Stylianos , Theodorakis Ioannis , Iliadis Efstratios , Karagkounidis Tilemachos , Koumantos Ioannis , Tatarakis Michael , Bakarezos Makis , Papadogiannis Nektarios A. , Dimitriou Vasilis
Published: April 2023

An integrated method, which combines Electronic Speckle Pattern Interferometry, impulse response measurements, finite element method simulations, and psychoacoustic tests, is proposed to evaluate the vibroacoustic behavior of a carbon fiber bouzouki. Three of the carbon fiber instruments are manufactured, and one is qualified via interferometric experimental measurements with reference to a traditional wooden bouzouki, which was evaluated for its sound and playability by the proposed method. Psychoacoustic tests were used to evaluate the sound and playability of the newly qualified carbon fiber bouzouki, which was further modeled by the finite element method and simulated. The simulation results agreed well with the experimental measurements. Furthermore, finite element simulation results of the qualified carbon fiber bouzouki were demonstrated with reference to the traditional wooden bouzouki experimental results, providing new findings crucial for the optimization of the manufacturing and the vibroacoustic behavior of the carbon fiber instrument. The proposed integrated method can be applied to a variety of carbon fiber stringed musical instruments.
Computer Aided Classifier of Colorectal Cancer on Histopatological Whole Slide Images Analyzing Deep Learning Architecture Parameters
Authors: Martínez-Fernandez Elena , Rojas-Valenzuela Ignacio , Valenzuela Olga , Rojas Ignacio
Published: April 2023

The diagnosis of different pathologies and stages of cancer using whole histopathology slide images (WSI) is the gold standard for determining the degree of tissue metastasis. The use of deep learning systems in the field of medical images, especially histopathology images, is becoming increasingly important. The training and optimization of deep neural network models involve fine-tuning parameters and hyperparameters such as learning rate, batch size (BS), and boost to improve the performance of the model in task-specific applications. Tuning hyperparameters is a major challenge in designing deep neural network models, having a large impact on the performance. This paper analyzes how the parameters and hyperparameters of a deep learning architecture affect the classification of colorectal cancer (CRC) histopathology images using the well-known VGG19 model. This paper also discusses the pre-processing of these images, such as the use of color normalization and stretching transformations on the data set. Among these hyperparameters, the most important neural network hyperparameter is the learning rate (LR). In this paper, different strategies for the optimization of LR are analyzed (both static and dynamic) and a new experiment based on the variation of LR is proposed (the relevance of dynamic strategies over fixed LR is highlighted), after each layer of the neural network together with decreasing variations according to the epochs. The results obtained are very remarkable, obtaining in the simulation an accurate system that achieves 96.4% accuracy on test images (for nine different tissue classes) using the triangular-cyclic learning rate.
Experimental Investigation on Reversible Swelling Mechanisms of Lithium-Ion Batteries under a Varying Preload Force
Authors: Michelini Emanuele , Höschele Patrick , Heindl Simon Franz , Erker Simon , Ellersdorfer Christian
Published: April 2023

The safety of lithium-ion batteries has to be guaranteed over the complete lifetime considering geometry changes caused by reversible and irreversible swellings and degradation mechanisms. An understanding of the pressure distribution and gradients is necessary to optimize battery modules and avoid local degradation bearing the risk of safety-relevant battery changes. In this study, the pressure distribution of two fresh lithium-ion pouch cells was measured with an initial preload force of 300 or 4000 N. Four identical cells were electrochemically aged with a 300 or 4000 N preload force. The irreversible thickness change was measured during aging. After aging, the reversible swelling behavior was investigated to draw conclusions on how the pressure distribution affected the aging behavior. A novel test setup was developed to measure the local cell thickness without contact and with high precision. The results suggested that the applied preload force affected the pressure distribution and pressure gradients on the cell surface. The pressure gradients were found to affect the locality of the irreversible swelling. Positions suffering from large pressure variations and gradients increased strongly in thickness and were affected in terms of their reversible swelling behavior. In particular, the edges of the investigated cells showed a strong thickness increase caused by pressure peaks.
Deep Reinforcement Learning-Based Method for Joint Optimization of Mobile Energy Storage Systems and Power Grid with High Renewable Energy Sources
Authors: Ding Yongkang , Chen Xinjiang , Wang Jianxiao
Published: April 2023

The joint optimization of power systems, mobile energy storage systems (MESSs), and renewable energy involves complex constraints and numerous decision variables, and it is difficult to achieve optimization quickly through the use of commercial solvers, such as Gurobi and Cplex. To address this challenge, we present an effective joint optimization approach for MESSs and power grids that consider various renewable energy sources, including wind power (WP), photovoltaic (PV) power, and hydropower. The integration of MESSs could alleviate congestion, minimize renewable energy waste, fulfill unexpected energy demands, and lower the operational costs for power networks. To model the entire system, a mixed-integer programming (MIP) model was proposed that considered both the MESSs and the power grid, with the goal of minimizing costs. Furthermore, this research proposed a highly efficient deep reinforcement learning (DRL)-based method to optimize route selection and charging/discharging operations. The efficacy of the proposed method was demonstrated through many numerical simulations.
Long Non-Coding RNAs in Hypoxia and Oxidative Stress: Novel Insights Investigating a Piglet Model of Perinatal Asphyxia
Authors: Grebstad Tune Benedicte , Melheim Maria , Åsegg-Atneosen Monica , Dotinga Baukje , Saugstad Ola Didrik , Solberg Rønnaug , Baumbusch Lars Oliver
Published: April 2023

Birth asphyxia is the leading cause of death and disability in young children worldwide. Long non-coding RNAs (lncRNAs) may provide novel targets and intervention strategies due to their regulatory potential, as demonstrated in various diseases and conditions. We investigated cardinal lncRNAs involved in oxidative stress, hypoxia, apoptosis, and DNA damage using a piglet model of perinatal asphyxia. A total of 42 newborn piglets were randomized into 4 study arms: (1) hypoxia–normoxic reoxygenation, (2) hypoxia–3 min of hyperoxic reoxygenation, (3) hypoxia–30 min of hyperoxic reoxygenation, and (4) sham-operated controls. The expression of lncRNAs BDNF-AS, H19, MALAT1, ANRIL, TUG1, and PANDA, together with the related target genes VEGFA, BDNF, TP53, HIF1α, and TNFα, was assessed in the cortex, the hippocampus, the white matter, and the cerebellum using qPCR and Droplet Digital PCR. Exposure to hypoxia–reoxygenation significantly altered the transcription levels of BDNF-AS, H19, MALAT1, and ANRIL. BDNF-AS levels were significantly enhanced after both hypoxia and subsequent hyperoxic reoxygenation, 8% and 100% O2, respectively. Our observations suggest an emerging role for lncRNAs as part of the molecular response to hypoxia-induced damages during perinatal asphyxia. A better understanding of the regulatory properties of BDNF-AS and other lncRNAs may reveal novel targets and intervention strategies in the future.
Study on the Geographic Variation and Trophic Variation of Todarodes pacificus in Different Areas Based on Stable Isotope Information from the Gladius
Authors: Lu Huajie , Wang Rui , Chen Jing , Ou Yuzhe , Zhao Maolin , Zhang Biqiang
Published: April 2023

The Japanese flying squid (Todarodes pacificus) is an important cephalopod in the northwest Pacific Ocean. In this study, the proostracum of the gladius of T. pacificus samples collected by Chinese squid fishing vessels in the East China Sea and the Sea of Japan in August and December 2018 were continuously cut, and stable isotope values of the cut fragments were used to analyze the migration path and feeding ecology of T. pacificus. The results showed that when the proostracum grew to 120 mm from the distal end, T. pacificus began to migrate. In the East China Sea, T. pacificus migrated to low latitudes and nearshore areas, and the trophic level of their food showed no large changes during migration. In the Sea of Japan, T. pacificus migrated to high latitudes and offshore areas, and the trophic level of their food showed a decreasing trend during migration. There was no significant difference in migration or feeding ecology between females and males, but the competitive capacity of the females may be stronger than that of the males. The results provided a scientific basis for the scientific management and development of T. pacificus resources.
Trajectories of Allopregnanolone and Allopregnanolone to Progesterone Ratio across the Six Subphases of Menstrual Cycle
Authors: Hamidovic Ajna , Davis John , Soumare Fatimata , Datta Avisek , Naveed Aamina
Published: April 2023

Background: Allopregnanolone is one of the most studied neuroactive steroids; yet, despite its relevance to neuropsychiatric research, it is not known how it, as well as its ratio to progesterone, varies across all six subphases of the menstrual cycle. Two enzymes—5α-dihydroprogesterone and 5α-reductase—convert progesterone to allopregnanolone, and, based on immunohistochemical studies in rodents, the activity of 5α-reductase is considered the rate-limiting step in the formation of allopregnanolone. It is not clear, however, whether the same phenomenon is observed across to the menstrual cycle, and, if so, at what point this takes place. Methods: Thirty-seven women completed the study during which they attended eight clinic visits across one menstrual cycle. We analyzed their allopregnanolone and progesterone serum concentrations using ultraperformance liquid chromatography–tandem mass spectrometry, and we implemented a validated method to realign the data from the original eight clinic study visits, following which we imputed the missing data. Hence, we characterized allopregnanolone concentrations, and the ratio of allopregnanolone:progesterone at six menstrual cycle subphases: (1) early follicular, (2) mid-follicular, (3) periovulatory, (4) early luteal, (5) mid-luteal, and (6) late luteal. Results: There were significant differences in allopregnanolone levels between (1) early follicular and early luteal, (2) early follicular and mid-luteal, (3) mid-follicular and mid-luteal, (4) periovulatory and mid-luteal, and (5) mid-luteal and late luteal. We detected a sharp drop in allopregnanolone:progesterone ratio in the early luteal subphase. Within the luteal subphase, the ratio was the lowest in the mid-luteal subphase. Conclusions: Allopregnanolone concentrations are the most distinct, relative to the other subphases, in the mid-luteal subphase. The shape of the allopregnanolone trajectory across the cycle is similar to that of progesterone; however, the proportion of the two neuroactive steroid hormones is drastically different due to enzymatic saturation, which takes place at the start of the early luteal subphase, but continuing through, and peaking, in the mid-luteal subphase. Hence, the estimated activity of 5α-reductase decreases, but does not cease, at any point across the menstrual cycle.
Glucocorticoid Receptor and Ovarian Cancer: From Biology to Therapeutic Intervention
Authors: Buonaiuto Roberto , Neola Giuseppe , Cecere Sabrina Chiara , Caltavituro Aldo , Cefaliello Amedeo , Pietroluongo Erica , De Placido Pietro , Giuliano Mario , Arpino Grazia , De Angelis Carmine
Published: April 2023

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies worldwide. Fortunately, recent advances in OC biology and the discovery of novel therapeutic targets have led to the development of novel therapeutic agents that may improve the outcome of OC patients. The glucocorticoid receptor (GR) is a ligand-dependent transcriptional factor known for its role in body stress reactions, energy homeostasis and immune regulation. Notably, evidence suggests that GR may play a relevant role in tumor progression and may affect treatment response. In cell culture models, administration of low levels of glucocorticoids (GCs) suppresses OC growth and metastasis. Conversely, high GR expression has been associated with poor prognostic features and long-term outcomes in patients with OC. Moreover, both preclinical and clinical data have shown that GR activation impairs the effectiveness of chemotherapy by inducing the apoptotic pathways and cell differentiation. In this narrative review, we summarize data related to the function and role of GR in OC. To this aim, we reorganized the controversial and fragmented data regarding GR activity in OC and herein describe its potential use as a prognostic and predictive biomarker. Moreover, we explored the interplay between GR and BRCA expression and reviewed the latest therapeutic strategies such as non-selective GR antagonists and selective GR modulators to enhance chemotherapy sensitivity, and to finally provide new treatment options in OC patients.
Facial Preparation of Cyclometalated Iridium (III) Nanowires as Highly Efficient Electrochemiluminescence Luminophores for Biosensing
Authors: Huang Yueyue , Doeven Egan H. , Chen Lifen , Yao Yuanyuan , Wang Yueliang , Lin Bingyong , Zeng Yanbo , Li Lei , Qian Zhaosheng , Guo Longhua
Published: April 2023

In this study, highly efficient ECL luminophores composed of iridium complex-based nanowires (Ir–NCDs) were synthesized via covalently linking bis(2-phenylpyridine)-(4-carboxypropyl-2,2′-bipyridyl) iridium(III) hexafluorophosphate with nitrogen-doped carbon quantum dots (NCDs). The ECL intensity of the nanowires showed a five-fold increase in ECL intensity compared with the iridium complex monomer under the same experimental conditions. A label-free ECL biosensing platform based on Ir–NCDs was established for Salmonella enteritidis (SE) detection. The ECL signal was quenched linearly in the range of 102–108 CFU/mL for SE with a detection limit of 102 CFU/mL. Moreover, the relative standard deviations (RSD) of the stability within and between batches were 0.98% and 3.9%, respectively. In addition, the proposed sensor showed high sensitivity, selectivity and stability towards SE in sheep feces samples with satisfactory results. In summary, the excellent ECL efficiency of Ir–NCDs demonstrates the prospects for Ir(III) complexes in bioanalytical applications.
Cognitive Processes and Resting-State Functional Neuroimaging Findings in High Schizotypal Individuals and Schizotypal Personality Disorder Patients: A Systematic Review
Authors: Zouraraki Chrysoula , Karamaouna Penny , Giakoumaki Stella G.
Published: April 2023

Ample research findings indicate that there is altered brain functioning in the schizophrenia spectrum. Nevertheless, functional neuroimaging findings remain ambiguous for healthy individuals expressing high schizotypal traits and patients with schizotypal personality disorder (SPD). The purpose of this systematic review was to identify patterns of task-related and resting-state neural abnormalities across these conditions. MEDLINE-PubMed and PsycINFO were systematically searched and forty-eight studies were selected. Forty studies assessed healthy individuals with high schizotypal traits and eight studies examined SPD patients with functional neuroimaging techniques (fNIRS; fMRI; Resting-state fMRI). Functional alterations in striatal, frontal and temporal regions were found in healthy individuals with high schizotypal traits. Schizotypal personality disorder was associated with default mode network abnormalities but further research is required in order to better conceive its neural correlates. There was also evidence for functional compensatory mechanisms associated with both conditions. To conclude, the findings suggest that brain dysfunctions are evident in individuals who lie along the subclinical part of the spectrum, further supporting the continuum model for schizophrenia susceptibility. Additional research is required in order to delineate the counterbalancing processes implicated in the schizophrenia spectrum, as this approach will provide promising insights for both conversion and protection from conversion into schizophrenia.
Research on Corrosion Rate Model of Reinforcement in Concrete under Chloride Ion Environments
Authors: Shi Ruoli , Pan Zhicheng , Lun Peiyuan , Zhan Yali , Nie Ziheng , Liu Yuzi , Mo Zongyun , He Zhijian
Published: April 2023

In a chloride environment, taking reinforced concrete structures as the research object, the corrosion rate of reinforcement determines its corrosion expansion because multiple coupling parameters will affect the corrosion rate of reinforcement, which is extremely difficult to effectively predict. In this paper, 144 sets of experimental data were collected and sorted out by reading the relevant literature, and six empirical models for predicting the corrosion rate of steel bars were compared and analyzed based on these experimental data. Based on the investigations, a new empirical model is proposed for predicting the corrosion rate of reinforcement, and the relevant influencing factors are considered in the new model. By comparing the 144 sets of experimental data and 90 experimental data for this paper, the new prediction model can well predict the corrosion rate of reinforcement. Furthermore, the time variability of the new prediction model is verified. The probability distribution characteristics of seven prediction models are obtained through model error analysis, which provides a theoretical basis for the next step of concrete cover cracking and reliability analysis.
Deep Learning Model Based on Contrast-Enhanced Computed Tomography Imaging to Predict Postoperative Early Recurrence after the Curative Resection of a Solitary Hepatocellular Carcinoma
Authors: Kinoshita Masahiko , Ueda Daiju , Matsumoto Toshimasa , Shinkawa Hiroji , Yamamoto Akira , Shiba Masatsugu , Okada Takuma , Tani Naoki , Tanaka Shogo , Kimura Kenjiro , Ohira Go , Nishio Kohei , Tauchi Jun , Kubo Shoji , Ishizawa Takeaki
Published: April 2023

We aimed to develop the deep learning (DL) predictive model for postoperative early recurrence (within 2 years) of hepatocellular carcinoma (HCC) based on contrast-enhanced computed tomography (CECT) imaging. This study included 543 patients who underwent initial hepatectomy for HCC and were randomly classified into training, validation, and test datasets at a ratio of 8:1:1. Several clinical variables and arterial CECT images were used to create predictive models for early recurrence. Artificial intelligence models were implemented using convolutional neural networks and multilayer perceptron as a classifier. Furthermore, the Youden index was used to discriminate between high- and low-risk groups. The importance values of each explanatory variable for early recurrence were calculated using permutation importance. The DL predictive model for postoperative early recurrence was developed with the area under the curve values of 0.71 (test datasets) and 0.73 (validation datasets). Postoperative early recurrence incidences in the high- and low-risk groups were 73% and 30%, respectively (p = 0.0057). Permutation importance demonstrated that among the explanatory variables, the variable with the highest importance value was CECT imaging analysis. We developed a DL model to predict postoperative early HCC recurrence. DL-based analysis is effective for determining the treatment strategies in patients with HCC.
Prognostic Role of the Intrahepatic Lymphatic System in Liver Cancer
Authors: Sakamoto Katsunori , Ogawa Kohei , Tamura Kei , Honjo Masahiko , Funamizu Naotake , Takada Yasutsugu
Published: April 2023

Although several prognosticators, such as lymph node metastasis (LNM), were reported for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the prognostic impact of intrahepatic lymphatic vessel invasion (LVI) in liver cancer has rarely been reported. We sought to clarify the prognostic impact of intrahepatic lymphatic system involvement in liver cancer. We systematically reviewed retrospective studies that described LVI and clinical outcomes of liver cancer and also included studies that investigated tumor-associated lymphangiogenesis. We conducted a meta-analysis using RevMan software (version 5.4.1; Cochrane Collaboration, Oxford, UK). The prognostic impact of intrahepatic LVI in HCC was not reported previously. However, tumor-associated lymphangiogenesis reportedly correlates with prognosis after HCC resection. The prognostic impact of intrahepatic LVI was reported severally for ICC and a meta-analysis showed that overall survival was poorer in patients with positive LVI than with negative LVI after resection of ICC. Lymphangiogenesis was also reported to predict unfavorable prognosis in ICC. Regarding colorectal liver metastases, LVI was identified as a poor prognosticator in a meta-analysis. A few reports showed correlations between LVI/lymphangiogenesis and LNM in liver cancer. LVI and lymphangiogenesis showed worse prognostic impacts for liver cancer than their absence, but further study is needed.
MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept
Authors: Gigante Elia , Cazier Hélène , Albuquerque Miguel , Laouirem Samira , Beaufrère Aurélie , Paradis Valérie
Published: April 2023

Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition.
Henry Gas Solubility Optimization Algorithm based Feature Extraction in Dermoscopic Images Analysis of Skin Cancer
Authors: Obayya Marwa , Alhebri Adeeb , Maashi Mashael , S. Salama Ahmed , Mustafa Hilal Anwer , Alsaid Mohamed Ibrahim , Osman Azza Elneil , Alneil Amani A.
Published: April 2023

Artificial Intelligence (AI) techniques have changed the general perceptions about medical diagnostics, especially after the introduction and development of Convolutional Neural Networks (CNN) and advanced Deep Learning (DL) and Machine Learning (ML) approaches. In general, dermatologists visually inspect the images and assess the morphological variables such as borders, colors, and shapes to diagnose the disease. In this background, AI techniques make use of algorithms and computer systems to mimic the cognitive functions of the human brain and assist clinicians and researchers. In recent years, AI has been applied extensively in the domain of dermatology, especially for the detection and classification of skin cancer and other general skin diseases. In this research article, the authors propose an Optimal Multi-Attention Fusion Convolutional Neural Network-based Skin Cancer Diagnosis (MAFCNN-SCD) technique for the detection of skin cancer in dermoscopic images. The primary aim of the proposed MAFCNN-SCD technique is to classify skin cancer on dermoscopic images. In the presented MAFCNN-SCD technique, the data pre-processing is performed at the initial stage. Next, the MAFNet method is applied as a feature extractor with Henry Gas Solubility Optimization (HGSO) algorithm as a hyperparameter optimizer. Finally, the Deep Belief Network (DBN) method is exploited for the detection and classification of skin cancer. A sequence of simulations was conducted to establish the superior performance of the proposed MAFCNN-SCD approach. The comprehensive comparative analysis outcomes confirmed the supreme performance of the proposed MAFCNN-SCD technique over other methodologies.
DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors
Authors: Shishparenok Anastasiya N. , Furman Vitalina V. , Zhdanov Dmitry D.
Published: April 2023

DNA nanotechnology has significantly advanced and might be used in biomedical applications, drug delivery, and cancer treatment during the past few decades. DNA nanomaterials are widely used in biomedical research involving biosensing, bioimaging, and drug delivery since they are remarkably addressable and biocompatible. Gradually, modified nucleic acids have begun to be employed to construct multifunctional DNA nanostructures with a variety of architectural designs. Aptamers are single-stranded nucleic acids (both DNAs and RNAs) capable of self-pairing to acquire secondary structure and of specifically binding with the target. Diagnosis and tumor therapy are prospective fields in which aptamers can be applied. Many DNA nanomaterials with three-dimensional structures have been studied as drug delivery systems for different anticancer medications or gene therapy agents. Different chemical alterations can be employed to construct a wide range of modified DNA nanostructures. Chemically altered DNA-based nanomaterials are useful for drug delivery because of their improved stability and inclusion of functional groups. In this work, the most common oligonucleotide nanomaterials were reviewed as modern drug delivery systems in tumor cells.
Outcomes of the Tall-Cell Variant of Papillary Thyroid Carcinoma in Patients with Different Ages: A 17-Year Mono-Institutional Experience
Authors: Proietti Agnese , Signorini Francesca , Giannini Riccardo , Poma Anello Marcello , Macerola Elisabetta , Torregrossa Liborio , Materazzi Gabriele , Basolo Alessio , Santini Ferruccio , Elisei Rossella , Viola David , Basolo Fulvio , Ugolini Clara
Published: April 2023

The tall-cell variant of papillary thyroid carcinoma (TCPTC) is the most common aggressive variant of papillary thyroid carcinoma (PTC) and typically occurs in older patients. In this study, we analyzed retrospectively the largest mono-institutional series of PTCs with tall-cell features (989 patients) over a 17-year period, re-evaluating tumors based on age at presentation and outcomes in different age groups. We divided patients into three age groups following different criteria (the criterion from the American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) guidelines, criterion for the statistical division into tertiles and adolescent/post-adolescent criterion) to analyze the clinicopathological characteristics in different age groups, especially in terms of recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). We obtained three main results: 1. the population is distributed among the different age groups, and therefore, this type of cancer is not exclusively found among those of an older age; 2. in the RFS analysis, we can see a higher probability of local recurrence in the younger and older groups and, unexpectedly, a lower probability of local recurrence in the “median age” group; and 3. in the DRFS analysis, we can observe a higher probability of distant recurrence in older patients. From a molecular perspective, no significant differences in the mutational status of BRAF were detected according to different age groups, while mutations in the TERT promoter were exclusively present in older patients of all age groups, highlighting the potential prognostic implications of TERT promoter mutations in PTCs. In conclusion, the results of this series confirm that TC morphology alone in PTCs does not have the same negative prognostic significance in the younger population as in the older population. The reason for these different outcomes remains unclear and needs further studies.
Critical Appraisal of Leibovich 2018 and GRANT Models for Prediction of Cancer-Specific Survival in Non-Metastatic Chromophobe Renal Cell Carcinoma
Authors: Piccinelli Mattia Luca , Morra Simone , Tappero Stefano , Cano Garcia Cristina , Barletta Francesco , Incesu Reha-Baris , Scheipner Lukas , Baudo Andrea , Tian Zhe , Luzzago Stefano , Mistretta Francesco Alessandro , Ferro Matteo , Saad Fred , Shariat Shahrokh F. , Carmignani Luca , Ahyai Sascha , Tilki Derya , Briganti Alberto , Chun Felix K. H. , Terrone Carlo , Longo Nicola , de Cobelli Ottavio , Musi Gennaro , Karakiewicz Pierre I.
Published: April 2023

Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC.
The Role of Exosomes in Epithelial–to-Mesenchymal Transition and Cell Functional Properties in Head and Neck Cancer
Authors: Mastronikolis Nicholas S. , Kyrodimos Efthymios , Spyropoulou Despoina , Delides Alexander , Giotakis Evangelos , Piperigkou Zoi , Karamanos Nikos K.
Published: April 2023

Exosomes are nanosized vesicles that are produced in normal and cancer cells, promoting intracellular communication. In head and neck cancer (HNC), exosomes are involved in many undesirable events of cancer development and progression, including angiogenesis, tumor microenvironment (TME) remodeling, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, extracellular matrix (ECM) degradation, and drug resistance. Exosomes are involved in altering the signaling pathways in recipient cells by the cargoes they carry. Proteins, lipids, and nucleic acids such as DNA fragments and RNAs (i.e., mRNAs, miRNAs, and long non-coding RNAs) are carried in the exosomes to promote cell communication. EMT is a critical cellular process in which epithelial cells are forced to become mesenchymal cells by the actions of SNAIL/SLUG, TWIST, and ZEB family transcription factors carried in exosomes that facilitate metastasis. In this critical review, we focused on exosome biogenesis, their cargoes, and their involvement in EMT induction and metastasis during HNC. Insights into exosome isolation and characterization, as well as their key role in ECM remodeling and degradation, are also presented and critically discussed. More importantly, this article addresses the role of exosomes in HNC and drug resistance induced in drug-sensitive cancer cells. In addition, exosomes have a great potential to be used as diagnostic and therapeutic tools. A better understanding on exosome biogenesis, composition, and functions in HNC will aid in developing novel therapeutic strategies to treat HNC, overcome therapy resistance, and avoid metastasis, which is a significant cause of cancer death.
Impact of Pre- and Post-Processing Steps for Supervised Classification of Colorectal Cancer in Hyperspectral Images
Authors: Tkachenko Mariia , Chalopin Claire , Jansen-Winkeln Boris , Neumuth Thomas , Gockel Ines , Maktabi Marianne
Published: April 2023

Background: Recent studies have shown that hyperspectral imaging (HSI) combined with neural networks can detect colorectal cancer. Usually, different pre-processing techniques (e.g., wavelength selection and scaling, smoothing, denoising) are analyzed in detail to achieve a well-trained network. The impact of post-processing was studied less. Methods: We tested the following methods: (1) Two pre-processing techniques (Standardization and Normalization), with (2) Two 3D-CNN models: Inception-based and RemoteSensing (RS)-based, with (3) Two post-processing algorithms based on median filter: one applies a median filter to a raw predictions map, the other applies the filter to the predictions map after adopting a discrimination threshold. These approaches were evaluated on a dataset that contains ex vivo hyperspectral (HS) colorectal cancer records of 56 patients. Results: (1) Inception-based models perform better than RS-based, with the best results being 92% sensitivity and 94% specificity; (2) Inception-based models perform better with Normalization, RS-based with Standardization; (3) Our outcomes show that the post-processing step improves sensitivity and specificity by 6.6% in total. It was also found that both post-processing algorithms have the same effect, and this behavior was explained. Conclusion: HSI combined with tissue classification algorithms is a promising diagnostic approach whose performance can be additionally improved by the application of the right combination of pre- and post-processing.
α-Synuclein Preformed Fibrils Bind to β-Neurexins and Impair β-Neurexin-Mediated Presynaptic Organization
Authors: Feller Benjamin , Fallon Aurélie , Luo Wen , Nguyen Phuong Trang , Shlaifer Irina , Lee Alfred Kihoon , Chofflet Nicolas , Yi Nayoung , Khaled Husam , Karkout Samer , Bourgault Steve , Durcan Thomas M. , Takahashi Hideto
Published: April 2023

Synucleinopathies form a group of neurodegenerative diseases defined by the misfolding and aggregation of α-synuclein (α-syn). Abnormal accumulation and spreading of α-syn aggregates lead to synapse dysfunction and neuronal cell death. Yet, little is known about the synaptic mechanisms underlying the α-syn pathology. Here we identified β-isoforms of neurexins (β-NRXs) as presynaptic organizing proteins that interact with α-syn preformed fibrils (α-syn PFFs), toxic α-syn aggregates, but not α-syn monomers. Our cell surface protein binding assays and surface plasmon resonance assays reveal that α-syn PFFs bind directly to β-NRXs through their N-terminal histidine-rich domain (HRD) at the nanomolar range (KD: ~500 nM monomer equivalent). Furthermore, our artificial synapse formation assays show that α-syn PFFs diminish excitatory and inhibitory presynaptic organization induced by a specific isoform of neuroligin 1 that binds only β-NRXs, but not α-isoforms of neurexins. Thus, our data suggest that α-syn PFFs interact with β-NRXs to inhibit β-NRX-mediated presynaptic organization, providing novel molecular insight into how α-syn PFFs induce synaptic pathology in synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies.
High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy
Authors: DeWulf Bram , Minsart Laurens , Verdonk Franck , Kruys Véronique , Piagnerelli Michael , Maze Mervyn , Saxena Sarah
Published: April 2023

Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood–brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.
RBD-Modified Polyaniline-Based Label-Free Immunosensor for Sensitive Impedimetric Detection of Anti-SARS-CoV-2 Antibodies
Authors: Romih Tea , Tasić Nikola , Bibič Lea , Beltram Ajda , Fazarinc Ika , Benčina Mojca , Jerala Roman , Hočevar Samo B.
Published: April 2023

The emergence of the SARS-CoV-2 virus and the associated pandemic has affected the entire human population. Human susceptibility to the virus has highlighted a tremendous need for affordable diagnostic systems to manage the pandemic and monitor the effectiveness of vaccination. We have developed a simple and label-free electrochemical immunosensor for the detection of human anti-SARS-CoV-2 IgG antibodies, which consists of a supporting screen-printed carbon electrode (SPCE) modified with an electrodeposited polyaniline film and glutaraldehyde, allowing effective immobilization of the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) as a biorecognition element. The impedimetric immunosensor showed a linear response over a wide concentration range of 0.01–10 μg mL−1, that is, 67 pM–6.7 nM, with a low detection limit of 25.9 pM. A dual working electrode configuration with a built-in negative control unit was demonstrated for practical field applications. The immunosensor was successfully used in a real serum sample from an infected patient and showed good reproducibility and fair agreement with ELISA. An optional amplification step with secondary goat anti-human IgG antibodies was demonstrated, resulting in an extended linear range and a detection limit as low as 0.93 pM.
Corrosion Behaviors of N80 and 1Cr Tubing Steels in CO2 Containing Downhole Environment—A Case Study of Underground Gas Storage in LiaoHe Oil Field
Authors: Liu Jianfeng , Li Minghui , He Mengqi , Ma Zelin , Li Kepei , Wang Ling , Li Guotao , Zhou Liguo , Zhang Shaohui , Yan Wei
Published: April 2023

In order to evaluate the effect of chromium content in carbon steel on the corrosion resistance of carbon steel materials, the corrosion behavior of 1Cr and N80 steels was investigated in this study by immersion weight loss method under three different CO2 partial pressure and temperature conditions in formation water for 72, 168 and 336 h. Detailed material surface morphological characterization was performed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and confocal laser scanning microscopy (CLSM). The results show that the pitting corrosion of N80 carbon steel is serious at medium temperature and low CO2 partial pressure (50 °C, 0.30 MPa), and the corrosion rate is significantly higher than that of 1Cr steel. However, at high-temperature and high CO2 partial pressure (100 °C/0.63 MPa and 114 °C/0.73 MPa), 1Cr steel is more inclined to the mesa corrosion dominated by local corrosion characteristics, and the corrosion rate is seriously higher than that of N80 steel with uniform corrosion. From the experimental results, we can know the corrosion resistance of carbon steel and 1Cr steel is not only affected by the corrosion environment, but also depends on the formation process of the product film, as well as its compactness and integrity characteristics. At low-temperature and low CO2 partial pressure, 1 wt.% chromium content can provide a certain degree of corrosion resistance, while high temperature and high partial pressure can broaden the application window of carbon steel N80 and weaken the corrosion inhibition effect of chromium.
First-Principles Studies on the Physical Properties of the Half Heusler RbNbCd and RbNbZn Compounds: A Promising Material for Thermoelectric Applications
Authors: Behera Debidatta , Azzouz-Rached Ahmed , Bouhenna Abdessalem , Salah Mostafa M. , Shaker Ahmed , Mukherjee Sanat Kumar
Published: April 2023

This work focuses on study of the structural, electronic, thermodynamic and thermoelectric properties of RbNbCd and RbNbZn Half Heusler (HH), utilizing a full-potential linearized augmented plane wave (FP-LAPW) approach and the Boltzmann transport equation using a constant relaxation time approximation within the context of density functional theory (DFT) as embedded in the WIEN2k code. The structural analysis employed the generalized gradient approximation (GGA) and considered the Birch Murnaghan equation of state (EOS), which results in the stable phase for RbNbCd and RbNbZn. The positive phonon spectra indicate the dynamical stability of the studied RbNbCd and RbNbZn. The compounds under investigation that have no bandgap are metallic, as evidenced by their electronic properties. Their mechanical and thermal stability as well as their anisotropic and ductile character are confirmed by the various elastic and thermodynamic parameters. The lattice thermal conductivity has been calculated. This thorough analysis demonstrates the applicability of the studied RbNbCd and RbNbZn for thermoelectric applications.