bluuebunny/crossref_metadata_2025 huggingface dataset:
A Progressive Deep Neural Network Training Method for Image Classification with Noisy Labels
Authors: Yan Xuguo , Xia Xuhui , Wang Lei , Zhang Zelin
Published: December 2022

Deep neural networks (DNNs) require large amounts of labeled data for model training. However, label noise is a common problem in datasets due to the difficulty of classification and high cost of labeling processes. Introducing the concepts of curriculum learning and progressive learning, this paper presents a novel solution that is able to handle massive noisy labels and improve model generalization ability. It proposes a new network model training strategy that considers mislabeled samples directly in the network training process. The new learning curriculum is designed to measures the complexity of the data with their distribution density in a feature space. The sample data in each category are then divided into easy-to-classify (clean samples), relatively easy-to-classify, and hard-to-classify (noisy samples) subsets according to the smallest intra-class local density with each cluster. On this basis, DNNs are trained progressively in three stages, from easy to hard, i.e., from clean to noisy samples. The experimental results demonstrate that the accuracy of image classification can be improved through data augmentation, and the classification accuracy of the proposed method is clearly higher than that of standard Inception_v2 for the NEU dataset after data augmentation, when the proportion of noisy labels in the training set does not exceed 60%. With 50% noisy labels in the training set, the classification accuracy of the proposed method outperformed recent state-of-the-art label noise learning methods, CleanNet and MentorNet. The proposed method also performed well in practical applications, where the number of noisy labels was uncertain and unevenly distributed. In this case, the proposed method not only can alleviate the adverse effects of noisy labels, but it can also improve the generalization ability of standard deep networks and their overall capability.
Radioactivity Content and Dosimetric Assessment in Bovine Meat from the Calabria Region, Southern Italy
Authors: Caridi Francesco , Venuti Valentina , Paladini Giuseppe , D’Agostino Maurizio , Belvedere Alberto , Marguccio Santina , Majolino Domenico
Published: December 2022

In this article, the assessment of the radioactivity content in bovine meat from the Calabria region, Southern Italy, was performed. For this purpose, High Purity Germanium (HPGe) gamma spectrometry measurements were carried out in order to investigate any possible radioactive contamination by natural (40K) and anthropogenic (137Cs) radionuclides. Experimental mean values were found to be in the range from (78.9 ± 10.5) Bq kg−1 to (88.2 ± 12.5) Bq kg−1 for 40K and lower than the minimum detectable activity (MDA) in all cases for 137Cs, respectively. Moreover, any possible radiological health risk was also estimated, by calculating the total annual effective dose due to the ingestion of bovine meat by adult members of the population and by comparing it with the total natural radioactivity value (external + internal) for humans. Obtained values are in the range from 10.3 µSv y−1 to 11.5 µSv y−1, several orders of magnitude lower than the value of the total exposure to natural radioactivity for human beings, i.e., 2.4 mSv y−1. It is worth noting that the used approach could be used, in principle, for the evaluation of the radiological risk due to the presence of radionuclides in a large variety of food samples of particular interest, and thus it can constitute a guideline for investigations focused on the monitoring of food quality.
Hybrid Multimodal Medical Image Fusion Method Based on LatLRR and ED-D2GAN
Authors: Zhou Tao , Li Qi , Lu Huiling , Zhang Xiangxiang , Cheng Qianru
Published: December 2022

In order to better preserve the anatomical structure information of Computed Tomography (CT) source images and highlight the metabolic information of lesion regions in Positron Emission Tomography (PET) source images, a hybrid multimodal medical image fusion method (LatLRR-GAN) based on Latent low-rank representation (LatLRR) and the dual discriminators Generative Adversarial Network (ED-D2GAN) is proposed. Firstly, considering the denoising capability of LatLRR, source images were decomposed by LatLRR. Secondly, the ED-D2GAN model was put forward as the low-rank region fusion method, which can fully extract the information contained by the low-rank region images. Among them, encoder and decoder networks were used in the generator; convolutional neural networks were also used in dual discriminators. Thirdly, a threshold adaptive weighting algorithm based on the region energy ratio is proposed as the salient region fusion rule, which can improve the overall sharpness of the fused image. The experimental results show that compared with the best methods of the other six methods, this paper is effective in multiple objective evaluation metrics, including the average gradient, edge intensity, information entropy, spatial frequency and standard deviation. The results of the two experiments are improved by 35.03%, 42.42%, 4.66%, 8.59% and 11.49% on average.
Assessment of the Sympathetic Detonation of Blasting Caps
Authors: Trană Eugen , Lupoae Marin , Iftimie Bogdan , Casapu Alexandru Cătălin
Published: December 2022

The neutralization of improvised explosive devices (IEDs) involves the use of disrupting agents propelled explosively. Due to the special nature of such materials, a proper investigation of the parts most susceptible to sympathetic detonation is in order. The initiation of IEDs is caused by detonation products, shock waves, and propelled disruptive agents. In this paper, initiation of IED composition (acceptor charge) due to the neutralization system’s (donor charge’s) explosive charge detonation is evaluated based on the influence of the first two of the three above-mentioned factors. One of the most susceptible components of IEDs to sympathetic initiation is the blasting cap. Based on an experimental and numerical mix approach, blasting cap tendency to sympathetic detonation in open field had been investigated. The suitability of critical energy fluence and Chapman–Jouguet threshold criteria to the sympathetic detonation tendency of blasting caps was investigated. Experimental and numerical/analytical results describing the phenomenon are in agreement.
A Spaceborne Mounting Method for Fixing a Cubic Fabry–Pérot Cavity in Ultra-Stable Lasers
Authors: Zhao Pengyang , Deng Jiuchang , Xing Chengwen , Meng Fanchao , Meng Lingqiang , Xie Yong , Chen Long , Liu Tao , Bian Wei , Yin Xiongfei , Qi Hongxing , Jia Jianjun , Zhang Shougang , Wang Jianyu
Published: December 2022

A spaceborne mounting method for fixing a 100 × 100 × 100 mm cubic Fabry–Pérot (FP) cavity is presented. The method constrains the FP cavity in eight directions with a titanium bracket, PEEK gaskets, and vacuum glue. Three criteria were proposed for judging whether the FP cavity is offset or not during aerospace vibration tests. Results indicate that the proposed method is a reliable, robust, and stable way to fix a cubic FP cavity in ultra-stable lasers (USLs). This approach paves the way for the use of USLs in space.
Generalization of ALMM Based Learning Method for Planning and Scheduling
Authors: Gomolka Zbigniew , Dudek-Dyduch Ewa , Zeslawska Ewa
Published: December 2022

This paper refers to a machine learning method for solving NP-hard discrete optimization problems, especially planning and scheduling. The method utilizes a special multistage decision process modeling paradigm referred to as the Algebraic Logical Metamodel based learning methods of Multistage Decision Processes (ALMM). Hence, the name of the presented method is the ALMM Based Learning method. This learning method utilizes a specifically built local multicriterion optimization problem that is solved by means of scalarization. This paper describes both the development of such local optimization problems and the concept of the learning process with the fractional derivative mechanism itself. It includes proofs of theorems showing that the ALMM Based Learning method can be defined for a much broader problem class than initially assumed. This significantly extends the range of the prime learning method applications. New generalizations for the prime ALMM Based Learning method, as well as some essential comments on a comparison of Reinforcement Learning with the ALMM Based Learning, are also presented.
Jet Grouping of Linear-Shaped Charges and Penetration Performance
Authors: Lim Seokbin , Baldovi Philipp , Rood Christopher
Published: December 2022

There have been many studies on the penetration performance of conical-shaped charges (CSCs) in various applications. These studies have led to a great deal of improvement, and even breakthroughs, in the design of CSCs. These studies have also positively affected the design of linear-shaped charges (LSCs), but due to the comparatively low penetration performance of LSCs there has been little theory-based scientific study of their penetration performance. In this paper, empirically observed field testing data are presented, including the details of the penetration performance and configuration of the LSC jet against UHMW-PE (ultra-high molecular weight polyethylene) targets using a series of flash X-ray exposures. These findings are compared to the previously published theoretical analysis in order to understand the nature of the formation, penetration, and classification/grouping of LSC jets. After a series of empirical and theoretical investigations, it was concluded that the LSC jet can be grouped depending on the jet particulation and distribution pattern, and each jet group exhibits different penetration performance. The relationship between liner collapse angle and jet segment density suggests potential room for performance improvement.
Aflatoxin B1 Binding by Lactic Acid Bacteria in Protein-Rich Plant Material Fermentation
Authors: Rämö Sari , Kahala Minna , Joutsjoki Vesa
Published: December 2022

At the same time as the strong ambition to improve sustainability and the healthiness of food systems through a transition towards a more plant-based diet, climate change is increasing the risk of plant diseases. Consequently, mycotoxigenic fungi have become a food safety issue of major importance. A variety of strategies to suppress fungal growth in the pre- and postharvest stages of plant production have been established, and the potential of various biological methods has been assessed to ensure food safety. Of the various food microbes, lactic acid bacteria are known for their capacity to suppress the growth of toxigenic fungi and adsorb free mycotoxins. The current study showed that lactic acid fermentation could mitigate aflatoxin risk in plant-based foods through a reduction in free aflatoxin B1. In line with previous studies, in which Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) was shown to reduce the level of free aflatoxin B1 in vitro, L. plantarum was shown to achieve up to a 90% reduction in free aflatoxin B1 in food fermentation. The results showed that traditional lactic acid fermentation, using L. plantarum as the starter strain, could be applied to mitigate aflatoxin B1 contamination risk in proteinaceous plant-based foodstuffs. In a wider context, fermentation using selected strains of lactic acid bacteria as starters could also enhance the availability of nutritious and safer food in terms of mycotoxin risk in low-income countries.
Penetration Depth of Initiated and Non-Initiated Diode Lasers in Bovine Gingiva
Authors: Romanos Georgios E. , Estrin Nathan E. , Lesniewski Agata , McClain Steve , Hou Wei
Published: December 2022

Background: This study aimed to evaluate the penetration depth of 445 and 970 nm diode lasers using both initiated and non-initiated fibers on bovine gingiva in an ex vivo model. Methods: In this in vitro experiment, 445 nm and 970 nm diode lasers were compared in pulsed (35 Hz, duty cycle: 50%) and continuous mode with both initiated and non-initiated tips. All experimental groups had laser output settings of 2 Watts with a 320 μm thick glass fiber utilized for delivery. Two posterior teeth were randomly selected from four bovine mandibles for each group. The teeth were irradiated for 30 s buccal and 30 s lingual before the gingiva was harvested for histological evaluation. Samples were fixed in 10% formalin and stained via elastin Van Gieson. Sections were examined microscopically to evaluate collagen denaturation due to thermal effects, which were measured and compared using a mixed-effect model with Tukey adjustment. Results: The 445 nm wavelength groups displayed significantly higher penetration depths when compared to the 970 nm wavelength groups. The initiated tip groups tended to display a lower penetration depth than non-initiated groups; however, these values were similar (p > 0.05) for the 445 nm pulsed lasers (initiated vs. non-initiated). Conclusions: We can conclude that the 445 nm laser wavelength displayed greater thermal denaturation in bovine gingiva ex vivo when compared to the 970 nm wavelength. Additionally, the pulsed settings displayed less thermal penetration depth when compared to the continuous emission modes of the same power output. However, additional studies are necessary to better compare initiated and non-initiated tips using the novel blue laser light.
Nanoformulation of Peptides for Pharmaceutical Applications: In Vitro and In Vivo Perspectives
Authors: Thimmiah Bhargavi Ram , Chien Belinda Tang Chien , Fui Kiew Siaw , Yon Lau Sie , Nallathambi Gobi , Jeevanandam Jaison , Danquah Michael K.
Published: December 2022

Peptides are short sequences of proteins consisting of two or more amino acids that are linked by peptide bonds. Peptide-based designs and drug deliveries can offer several advantages, such as antioxidant, antimicrobial, antihypertensive activities, along with immunomodulatory and antithrombotic properties, with hormone or drug-like potential. Peptide-based therapeutic formulations are used as drug candidates for the treatment of various diseases. However, there are several concerns associated with the efficacy of peptides in pharmaceutical design and delivery, including rapid degradation, limited solubility, and poor permeability. The nanoformulation of peptides has been identified as a promising approach for improving the stability of peptides and providing metabolic stability and bioavailability. This article provides an overview of the advances in the development of peptides for drug design and formulation applications. It discusses various peptide nanoformulation approaches as well as recent developments in the in vitro and in vivo analyses of nanoformulated peptides for pharmaceutical applications.
A Convex Hull-Based Machine Learning Algorithm for Multipartite Entanglement Classification
Authors: Wang Pingxun
Published: December 2022

Quantum entanglement becomes more complicated and capricious when more than two parties are involved. There have been methods for classifying some inequivalent multipartite entanglements, such as GHZ states and W states. In this paper, based on the fact that the set of all W states is convex, we approximate the convex hull by some critical points from the inside and propose a method of classification via the tangent hyperplane. To accelerate the calculation, we bring ensemble learning of machine learning into the algorithm, thus improving the accuracy of the classification.
Peritoneal Oxygenation as a Novel Technique for Extrapulmonary Ventilation; A Review and Discussion of the Literature
Authors: Colbourne James R. M. , Altoukhi Khaled H. , Morris David L.
Published: December 2022

The COVID-19 crisis has highlighted the difficulties that might occur when attempting to oxygenate patients who have suffered a severe pulmonary insult, including in the development of acute respiratory distress syndrome (ARDS). Traditional mechanical ventilation (MV) is effective; however, in severe cases of hypoxia, the use of rescue therapy, such as extracorporeal membrane oxygenation (ECMO), may be required but is also associated with significant complexity and complications. In this review, we describe peritoneal oxygenation; a method of oxygenation that exploits the peritoneum’s gas exchange properties in a fashion that is similar to peritoneal dialysis and has shown considerable promise in animal models. We have conducted a review of the available literature and techniques, including intraperitoneal perfluorocarbons, intraperitoneal jet ventilation, a continuous low-pressure oxygen system (PEROX) and the use of phospholipid-coated oxygen microbubbles (OMBs) through peritoneal microbubble oxygenation (PMO). We conclude that peritoneal oxygenation is a promising technique that warrants further investigation and might be used in clinical settings in the future.
Musing with Petric Bodies, Hanging on to Dear Life
Authors: Preston Julieanna
Published: December 2022

Musing with Petric Bodies, Hanging on to Dear Life is an essay that critically reflects on the live performance work “Becoming Boulder”, which occurred on 31 January 2015 as part of the Science Communication Art New Zealand Intercreate Symposium at New Plymouth, New Zealand. I performed a contact improvisation with a large andesite boulder, in a king tide, on a stormy day, at a culturally significant place for an extended period of time. Written using the present tense and as a dialogical text, the essay employs ekphrasis and practices geo-poetry to colour the scene and critically contextualise the potentials and limits of empathetic engagement with another form of organic assemblage. Complexities that come with being a foreigner or immigrant, well-versed in contemporary New Materialist discourse, and dwelling in a land rich with indigenous knowledge are voiced amongst gestures to get close to, identify with, and perform as an ancient, far from dead weight, body. While musing and critically contextualising on the potentials and limits of empathetic engagements, the essay seeks to exemplify the value of material situated learning that occurs in the space of making or doing of durational, experimental, site-responsive performance works.
Toward Probing Surface Magnetism with Highly Charged Ions
Authors: Dergham Perla , Aumayr Friedrich , Lamour Emily , Macé Stéphane , Prigent Christophe , Steydli Sébastien , Vernhet Dominique , Werl Matthias , Wilhelm Richard Arthur , Trassinelli Martino
Published: December 2022

X-rays produced during collisions between Highly Charged Ions (HCI) and sample surfaces can potentially be used to investigate the surface’s magnetic properties, taking advantage of the (partial) conservation of the spin of the electrons captured by the ion during the collision. We conducted studies to characterize the X-ray detection system and to determine, with a sub-degree accuracy, the incident angle between the incoming ions and the sample surfaces. A series of proof-of-principle experiments are presented involving an Ar17+ ion beam interacting with a nonmagnetic Si sample. The obtained X-ray spectra show a significant dependency in terms of X-ray yield and energy on the ion incidence angle. These findings will be used to guide future ion–magnetic surface studies.
The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury
Authors: Juckett Luke , Saffari Tiam Mana , Ormseth Benjamin , Senger Jenna-Lynn , Moore Amy M.
Published: December 2022

Peripheral nerve injuries (PNI) are common and often result in lifelong disability. The peripheral nervous system has an inherent ability to regenerate following injury, yet complete functional recovery is rare. Despite advances in the diagnosis and repair of PNIs, many patients suffer from chronic pain, and sensory and motor dysfunction. One promising surgical adjunct is the application of intraoperative electrical stimulation (ES) to peripheral nerves. ES acts through second messenger cyclic AMP to augment the intrinsic molecular pathways of regeneration. Decades of animal studies have demonstrated that 20 Hz ES delivered post-surgically accelerates axonal outgrowth and end organ reinnervation. This work has been translated clinically in a series of randomized clinical trials, which suggest that ES can be used as an efficacious therapy to improve patient outcomes following PNIs. The aim of this review is to discuss the cellular physiology and the limitations of regeneration after peripheral nerve injuries. The proposed mechanisms of ES protocols and how they facilitate nerve regeneration depending on timing of administration are outlined. Finally, future directions of research that may provide new perspectives on the optimal delivery of ES following PNI are discussed.
The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation
Authors: Gu Hyemin , An Hyun-Jin , Gwon Mi-Gyeong , Bae Seongjae , Zouboulis Christos C. , Park Kwan-Kyu
Published: December 2022

Acne vulgaris has a pathogenesis that involves increased sebum production and perifollicular inflammation. Sterol regulatory element-binding protein-1 (SREBP-1) and peroxisome proliferator activated receptor-γ (PPAR-γ) are transcription factors that regulate numerous genes involved in lipid biosynthesis. To improve a new therapeutic approach, we designed the SREBP/PPAR decoy oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequences for the SREBP and PPAR transcription factors. We aim to investigate the beneficial functions and the molecular mechanisms of the synthetic SREBP/PPAR decoy ODN in lipogenic models. C. acnes was intradermally injected with a 1.0 × 107 colony forming unit/20 μL. The synthetic SREBP/PPAR decoy ODN or scrambled decoy ODN (10 μg) was transferred via the mouse tail vein injection. SZ95 cells were transfected with 2 μg of synthetic ODNs. After transfection, the SZ95 cells were cultured in serum-free medium containing 20 ng/μL of insulin-like growth factor-1 (IGF)-1 for 24 h. To investigate the expression of gene and signaling pathways, we performed Western blotting. The distribution of the chimeric decoy ODN was confirmed by EMSA. Lipid levels were assessed by Nile red and Oil Red O staining. The cytokine levels were measured by ELISA kit. This study showed that C. acnes-injected mice and IGF-1-stimulated SZ95 cells exhibited increased expression of SREBP-1 and PPAR-γ compared to the normal controls. In contrast, the administration of the SREBP/PPAR chimeric decoy ODN significantly suppressed the upregulation of lipogenic genes. Furthermore, the SREBP/PPAR decoy ODN decreased the plasma cytokines and cytokine levels of total protein. These results suggested that the SREBP/PPAR decoy ODN exerts its anti-lipogenic effects by regulating lipid metabolism and by inhibiting lipogenesis through the inactivation of the SREBP and PPAR pathways. Therefore, the synthetic SREBP/PPAR ODN demonstrates substantial therapeutic feasibility for the treatment of acne vulgaris.
Spinal Astrocyte-Neuron Lactate Shuttle Contributes to the Pituitary Adenylate Cyclase-Activating Polypeptide/PAC1 Receptor-Induced Nociceptive Behaviors in Mice
Authors: Kambe Yuki , Youkai Masafumi , Hashiguchi Kohei , Sameshima Yoshimune , Takasaki Ichiro , Miyata Atsuro , Kurihara Takashi
Published: December 2022

We have previously shown that spinal pituitary adenylate cyclase-activating polypeptide (PACAP)/PACAP type 1 (PAC1) receptor signaling triggered long-lasting nociceptive behaviors through astroglial activation in mice. Since astrocyte-neuron lactate shuttle (ANLS) could be essential for long-term synaptic facilitation, we aimed to elucidate a possible involvement of spinal ANLS in the development of the PACAP/PAC1 receptor-induced nociceptive behaviors. A single intrathecal administration of PACAP induced short-term spontaneous aversive behaviors, followed by long-lasting mechanical allodynia in mice. These nociceptive behaviors were inhibited by 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of glycogenolysis, and this inhibition was reversed by simultaneous L-lactate application. In the cultured spinal astrocytes, the PACAP-evoked glycogenolysis and L-lactate secretion were inhibited by DAB. In addition, a protein kinase C (PKC) inhibitor attenuated the PACAP-induced nociceptive behaviors as well as the PACAP-evoked glycogenolysis and L-lactate secretion. Finally, an inhibitor for the monocarboxylate transporters blocked the L-lactate secretion from the spinal astrocytes and inhibited the PACAP- and spinal nerve ligation-induced nociceptive behaviors. These results suggested that spinal PAC1 receptor-PKC-ANLS signaling contributed to the PACAP-induced nociceptive behaviors. This signaling system could be involved in the peripheral nerve injury-induced pain-like behaviors.
Single-Cell RNA Sequencing Reveals Heterogeneity in the Tumor Microenvironment between Young-Onset and Old-Onset Colorectal Cancer
Authors: Li Gui-Ming , Xiao Guo-Zhong , Qin Peng-Fei , Wan Xing-Yang , Fu Yuan-Ji , Zheng Yi-Hui , Luo Min-Yi , Ren Dong-Lin , Liu Shi-Ping , Chen Hua-Xian , Lin Hong-Cheng
Published: December 2022

Background: The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. Compared with old-onset colorectal cancer (oCRC), yCRC has different clinical and molecular characteristics. However, the difference in the tumor microenvironment (TME) between yCRC and oCRC remains unclear. Methods: Fourteen untreated CRC tumor samples were subjected to single-cell RNA sequencing analysis. Results: B cells and naïve T cells are enriched in yCRC, while effector T cells and plasma cells are enriched in oCRC. Effector T cells of yCRC show decreased interferon-gamma response and proliferative activity; meanwhile, Treg cells in yCRC show stronger oxidative phosphorylation and TGF-β signaling than that in oCRC. The down-regulated immune response of T cells in yCRC may be regulated by immune and malignant cells, as we observed a downregulation of antigen presentation and immune activations in B cells, dendritic cells, and macrophages. Finally, we identified malignant cells in yCRC and oCRC with high heterogeneity and revealed their interactions with immune cells in the TME. Conclusions: Our data reveal significant differences of TME between yCRC and oCRC, of which the TME of yCRC is more immunosuppressive than oCRC. Malignant cells play an essential role in the formation of the suppressive tumor immune microenvironment.
Development of a Gastrointestinal-Myoelectrical-Activity-Based Nomogram Model for Predicting the Risk of Mild Cognitive Impairment
Authors: Li Baichuan , Ji Shuming , Peng Anjiao , Yang Na , Zhao Xia , Feng Peimin , Zhang Yunwu , Chen Lei
Published: December 2022

Mild cognitive impairment (MCI) is the prodromal stage and an important risk factor of Alzheimer’s disease (AD). Interventions at the MCI stage are significant in reducing the occurrence of AD. However, there are still many obstacles to the screening of MCI, resulting in a large number of patients going undetected. Given the strong correlation between gastrointestinal function and neuropsychiatric disorders, the aim of this study is to develop a risk prediction model for MCI based on gastrointestinal myoelectrical activity. The Mini-Mental State Examination and electrogastroenterography were applied to 886 participants in western China. All participants were randomly assigned to the training and validation sets in a ratio of 7:3. In the training set, risk variables were screened using LASSO regression and logistic regression, and risk prediction models were built based on nomogram and decision curve analysis, then validation was performed. Eight predictors were selected in the training set, including four electrogastroenterography parameters (rhythm disturbance, dominant frequency and dominant power ratio of gastric channel after meal, and time difference of intestinal channel after meal). The area under the ROC curve for the prediction model was 0.74 in the training set and 0.75 in the validation set, both of which exhibited great prediction ability. Furthermore, decision curve analysis displayed that the net benefit was more desirable when the risk thresholds ranged from 15% to 35%, indicating that the nomogram was clinically usable. The model based on gastrointestinal myoelectrical activity has great significance in predicting the risk of MCI and is expected to be an alternative to scales assessment.
Microplastic Effects on Thrombin–Fibrinogen Clotting Dynamics Measured via Turbidity and Thromboelastography
Authors: Tran Daniela Q. , Stelflug Nathan , Hall Abigail , Nallan Chakravarthula Tanmaye , Alves Nathan J.
Published: December 2022

Micro/nanoplastics, whether manufactured or resulting from environmental degradation, can enter the body through ingestion, inhalation, or dermal pathways. Previous research has found that nanoplastics with diameters of ≤100 nm can translocate into the circulatory system in a dose-dependent manner and potentially impact thrombosis and hemostasis. To investigate the direct effects of microplastics on fibrin clot formation, a simplified ex vivo human thrombin/fibrinogen clot model was utilized. The 100 nm polystyrene particles (non-functionalized [nPS] and aminated [aPS]) were preincubated (0–200 µg/mL) with either thrombin or fibrinogen, and fibrin clot formation was characterized via turbidity and thromboelastography (TEG). When the particles were preincubated with fibrinogen, little effect was observed for aPS or nPS on turbidity or TEG up through 100 µg/mL. TEG results demonstrated a significant impact on clot formation rate and strength, in the case of nPS preincubated with thrombin exhibiting a significant dose-dependent inhibitory effect. In conclusion, the presence of microplastics can have inhibitory effects on fibrin clot formation that are dependent upon both particle surface charge and concentration. Negatively charged nPS exhibited the most significant impacts to clot strength, turbidity, and rate of fibrin formation when first incubated with thrombin, with its impact being greatly diminished when preincubated with fibrinogen in this simplified fibrin clot model.
Identification, Screening, and Comprehensive Evaluation of Novel DPP-IV Inhibitory Peptides from the Tilapia Skin Gelatin Hydrolysate Produced Using Ginger Protease
Authors: Liu Wei , Wang Xinyu , Yang Wenning , Li Xueyan , Qi Dongying , Chen Hongjiao , Liu Huining , Yu Shuang , Pan Yanli , Liu Yang , Wang Guopeng
Published: December 2022

Purpose: Inhibition of dipeptidyl peptidase-IV (DPP-IV) is an effective therapy for treating type II diabetes (T2D) that has been widely applied in clinical practice. We aimed to evaluate the DPP-IV inhibitory properties of ginger protease hydrolysate (GPH) and propose a comprehensive approach to screen and evaluate DPP-IV inhibitors. Methods: We evaluated the in vitro inhibitory properties of fish skin gelatin hydrolysates produced by five proteases, namely, neutral protease, alkaline protease, bromelain, papain, and ginger protease, toward DPP-IV. We screened the most potent DPP-IV inhibitory peptide (DIP) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with in silico analysis. Next, surface plasmon resonance (SPR) technology was innovatively introduced to explore the interactions between DPP-IV and DIP, as well as the IC50. Furthermore, we performed oral administration of DIP in rats to study its in vivo absorption. Results: GPH displayed the highest degree of hydrolysis (20.37%) and DPP-IV inhibitory activity (65.18%). A total of 292 peptides from the GPH were identified using LC-MS/MS combined with de novo sequencing. Gly-Pro-Hyp-Gly-Pro-Pro-Gly-Pro-Gly-Pro (GPXGPPGPGP) was identified as the most potent DPP-IV inhibitory peptide after in silico screening (Peptide Ranker and molecular docking). Then, the in vitro study revealed that GPXGPPGPGP had a high inhibitory effect on DPP-IV (IC50: 1012.3 ± 23.3 μM) and exhibited fast kinetics with rapid binding and dissociation with DPP-IV. In vivo analysis indicated that GPXGPPGPGP was not absorbed intact but partially, in the form of dipeptides and tripeptides. Conclusion: Overall, the results suggested that GPH would be a natural functional food for treating T2D and provided new ideas for searching and evaluating potential antidiabetic compounds. The obtained GPXGPPGPGP can be structurally optimized for in-depth evaluation in animal and cellular experiments.
Transthyretin Cardiac Amyloidosis: A Cardio-Orthopedic Disease
Authors: Perfetto Federico , Zampieri Mattia , Bandini Giulia , Fedi Roberto , Tarquini Roberto , Santi Raffaella , Novelli Luca , Allinovi Marco , Argirò Alessia , Cappelli Francesco
Published: December 2022

Orthopaedic manifestations of wild-type transthyretin amyloidosis are frequent and characteristic, including idiopathic bilateral carpal tunnel syndrome, idiopathic lumbar canal stenosis, atraumatic rupture of the brachial biceps tendon, and, more rarely, finger disease and rotator cuff. These manifestations often coexisting in the same patient, frequently male and aged, steadily precede cardiac involvement inducing a rapidly progressive heart failure with preserved ejection fraction. Although transthyretin cardiac amyloidosis remains a cardiac relevant disease, these extracardiac localisation may increase diagnostic suspicion and allow for early diagnosis assuming the role of useful diagnostic red flags, especially in light of new therapeutic opportunities that can slow or stop the progression of the disease. For the cardiologist, the recognition of these extracardiac red flags is of considerable importance to reinforce an otherwise less emerging diagnostic suspicion. For orthopedists and rheumatologists, the presence in an old patient with or without clinical manifestations of cardiovascular disease, of an unexpected and inexplicable constellation of musculoskeletal symptoms, can represent a fundamental moment for an early diagnosis and treatment is improving a patient’s outcome.
Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience
Authors: Levra Stefano , Guida Giuseppe , Sprio Andrea Elio , Crosa Flavio , Ghio Paolo Carlo , Bertolini Francesca , Carriero Vitina , Albera Carlo , Ricciardolo Fabio Luigi Massimo
Published: December 2022

Pirfenidone and nintedanib are the only two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF). Both proved to be safe and well-tolerated in clinical trials, but real-world data and direct comparisons are scarce. This real-life study explored the safety profile of pirfenidone and nintedanib with a prolonged follow-up. We retrospectively collected clinical status, adverse events (AEs), and treatment changes from IPF patients who had started an antifibrotic treatment at our centre from December 2011 to December 2020, including 192 patients treated with pirfenidone and 89 with nintedanib. The majority of patients in both groups experienced one or more AEs during the follow-up. A higher proportion of AEs in the nintedanib group were effectively treated with behavioural modifications or additional medications compared with the pirfenidone group (52.5% vs. 40.6%, p = 0.04). Overall, a difference in the impact of AEs due to nintedanib versus pirfenidone resulted in a lower permanent discontinuation of therapy (8.3% vs. 18.3%, p = 0.02), with the latter being associated with a higher risk of drug discontinuation at 48 months after initiation (OR = 2.52, p = 0.03). Our study confirms the safety profile of antifibrotic drugs in IPF but highlights that AEs due to nintedanib are usually easier to manage and lead to fewer cases of permanent discontinuation of therapy.
Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein
Authors: Mamchur Aleksandra A. , Stanishneva-Konovalova Tatiana B. , Mokrushina Yuliana A. , Abrikosova Viktoria A. , Guo Yu , Zhang Hongkai , Terekhov Stanislav S. , Smirnov Ivan V. , Yaroshevich Igor A.
Published: December 2022

Variants of SARS-CoV-2 keep emerging and causing new waves of COVID-19 around the world. Effective new approaches in drug development are based on the binding of agents, such as neutralizing monoclonal antibodies to a receptor-binding domain (RBD) of SARS-CoV-2 spike protein. However, mutations in RBD may lower the affinity of previously developed antibodies. Therefore, rapid analysis of new variants and selection of a binding partner with high affinity is of great therapeutic importance. Here, we explore a computational approach based on molecular dynamics simulations and conformational clusterization techniques for the wild-type and omicron variants of RBD. Biochemical experiments support the hypothesis of the presence of several conformational states within the RBD assembly. The development of such an approach will facilitate the selection of neutralization drugs with higher affinity based on the primary structure of the target antigen.
Eph/Ephrin Promotes the Adhesion of Liver Tissue-Resident Macrophages to a Mimicked Surface of Liver Sinusoidal Endothelial Cells
Authors: Kohara Sho , Ogawa Kazushige
Published: December 2022

Kupffer cells are maintained via self-renewal in specific microenvironmental niches, primarily the liver sinusoidal endothelial cells (LSECs). In this study, we propagated tissue-resident macrophages (Mø) from mouse liver using mixed culture with hepatic fibroblastic cells. Propagated liver Mø express Id3, Lxra and Spic transcription factors, which are required for Kupffer cell characterization. Thus, Kupffer cell properties are likely to be maintained in liver Mø propagated using mixed culture with fibroblastic cells. We revealed (i) gene expression of certain Eph receptors and ephrin ligands including EphA2, ephrin-A1, EphB4, and ephrin-B1 in propagated liver Mø and primary LSECs, (ii) immunohistochemical localization of these Eph/ephrin member molecules indicating common expression in Kupffer cells and LSECs, and (iii) surface expression of several integrin α and β subunits, including α4β1, αLβ2, αMβ2, and αXβ2 integrin in propagated liver Mø and that of the corresponding ligands ICAM-1 and VCAM-1 in primary LSECs. Moreover, EphA/ephrin-A and EphB/ephrin-B interactions promoted liver Mø adhesion to the ICAM-1-adsorbed surface, which mimicked that of LSECs and may be implicated in the residence of Kupffer cells in the liver sinusoid. Further studies on regulating the residence and regeneration of Kupffer cells in related hepatic disorders are required to validate our findings.
Worsening Rhinosinusitis as a Prognostic Factor for Patients with Nasopharyngeal Carcinoma: A Retrospective Study
Authors: Lin Wei-Chieh , Kuo Yu-Hung , Hsu Chuan-Jen , Wu Hung-Pin , Hsu Yuan-Jhen
Published: December 2022

Rhinosinusitis is common in patients with nasopharyngeal carcinoma (NPC). Our study aimed to explore the role of rhinosinusitis severity in NPC prognosis. Medical records and radiologic examinations of 90 patients with NPC at a single medical center from 2009–2016 were retrospectively analyzed. The Lund–Mackay (L–M) score was obtained for each patient before and after 6 months of treatment. Rhinosinusitis diagnosis was based on L–M scores of ≥4. L–M score differences were calculated as pre-treatment rhinosinusitis (PRRS) minus post-treatment rhinosinusitis (PSRS). L–M score difference was sub-grouped into “L–M scores > 0”, “L–M scores = 0”, and “L–M scores < 0”. Clinical staging of our patients based on the American Joint Committee on Cancer 7th edition were: stage I in nine, stage II in seventeen, stage III in twenty-two, and stage IV in forty-two patients; twenty-seven (30%) patients had died. PRRS incidence was 34.4%, and PSRS was 36.7%. Median of L–M scores difference was 0 (−2.2). L–M score difference was an independent prognostic factor for the overall survival of patients with NPC (p < 0.05). Therefore, worsening rhinosinusitis was a prognostic factor for patients with NPC. Clinicians should consider NPC as a warning sign of poor prognosis during routine follow-ups.
TIGIT Expression on Intratumoral Lymphocytes Correlates with Improved Prognosis in Oral Squamous Cell Carcinoma
Authors: Eichberger Jonas , Spoerl Silvia , Spanier Gerrit , Erber Ramona , Taxis Juergen , Schuderer Johannes , Ludwig Nils , Fiedler Mathias , Nieberle Felix , Ettl Tobias , Geppert Carol I. , Reichert Torsten E. , Spoerl Steffen
Published: December 2022

(1) Background: T-cell immunoglobulin and ITIM domain (TIGIT) is a potential immunotherapeutic target in a variety of malignant entities, and antibody-based treatments are currently under investigation in clinical trials. While promising results were observed in patients with lung cancer, the role of TIGIT in oral squamous cell carcinoma (OSCC) as a biomarker as well as a therapeutic target remains elusive. Therefore, we evaluated the role of TIGIT as a prognostic factor in OSCC. (2) Methods: Here, we describe the results of a retrospective tissue microarray (TMA) OSCC cohort. Using immunohistochemistry, TIGIT expression was correlated with overall and recurrence-free survival (OAS and RFS, respectively). Additionally, in silico analysis was performed based on the TCGA Head and Neck Squamous Cell Carcinoma (HNSCC) cohort in order to correlate patients’ survival with TIGIT and CD274 (encoding for PD-L1) gene expression levels. (3) Results: Database analysis revealed a beneficial outcome in OAS for tumor patients with high intraepithelial CD3-TIGIT-expression (n = 327). Hereby, OAS was 53.9 months vs. 30.1 months for patients with lower TIGIT gene expression levels (p = 0.033). In our retrospective OSCC-TMA cohort, elevated TIGIT levels on CD3+ cells correlated significantly with improved OAS (p = 0.025) as well as distant RFS (p = 0.026). (4) Conclusions: This study introduces TIGIT as a novel prognostic factor in OSCC, indicating the improved outcome of OSCC patients relative to their increased TIGIT expression. TIGIT might provide therapeutic implications for future immunotherapy in advanced-stage OSCC patients.
SLC6A3, HTR2C and HTR6 Gene Polymorphisms and the Risk of Haloperidol-Induced Parkinsonism
Authors: Nedic Erjavec Gordana , Grubor Mirko , Zivkovic Maja , Bozina Nada , Sagud Marina , Nikolac Perkovic Matea , Mihaljevic-Peles Alma , Pivac Nela , Svob Strac Dubravka
Published: December 2022

Antipsychotic-induced parkinsonism (AIP) is the most common type of extrapyramidal side effect (EPS), caused by the blockage of dopamine receptors. Since dopamine availability might influence the AIP risk, the dopamine transporter (DAT) and serotonin receptors (5-HTRs), which modulate the dopamine release, may be also involved in the AIP development. As some of the individual differences in the susceptibility to AIP might be due to the genetic background, this study aimed to examine the associations of SLC6A3, HTR2C and HTR6 gene polymorphisms with AIP in haloperidol-treated schizophrenia patients. The Extrapyramidal Symptom Rating Scale (ESRS) was used to evaluate AIP as a separate entity. Genotyping was performed using a PCR, following the extraction of blood DNA. The results revealed significant associations between HTR6 rs1805054 polymorphism and haloperidol-induced tremor and rigidity. Additionally, the findings indicated a combined effect of HTR6 T and SLC6A3 9R alleles on AIP, with their combination associated with significantly lower scores of ESRS subscale II for parkinsonism, ESRS-based tremor or hyperkinesia and ESRS subscales VI and VIII. These genetic predictors of AIP could be helpful in better understanding its pathophysiology, recognizing the individuals at risk of developing AIP and offering personalized therapeutic strategies for the patients suffering from this EPS.
In-Situ Surface Modification of ITO Substrate via Bio-Inspired Mussel Chemistry for Organic Memory Devices
Authors: Gong Minglei , Li Wei , Fan Fei , Chen Yu , Zhang Bin
Published: December 2022

The development of organic memory devices, regarding factors such as structure construction, principle exploration, and material design, has become a powerful supplement to traditional silicon-based information storage. The in-situ growth of materials on substrate surfaces can achieve closer bonding between materials and electrodes. Bio-inspired by mussel chemistry, polydopamine (PDA) was self-assembled on a flexible substrate as a connecting layer, and 2-bromoiso-butyryl bromide (BiBB) was utilized as an initiator for the polymerization of an iridium complex via surface-initiated atom-transfer radical polymerization (SI-ATRP). A device with the structure of Al/PDA-PPy3Ir/ITO was constructed after the deposition of aluminum. The device exhibited a nonvolatile rewritable memory characteristic with a turn-on voltage of −1.0 V and an ON/OFF current ratio of 6.3 × 103. In addition, the memory performance of the Al/PDA-PPy3Ir/ITO device remained stable at bending states due to the intrinsic flexibility of the active layer, which can be expanded into the establishment of flexible memory devices. Spectroscopy and electrochemical characterization suggested that the resistive memory properties of the device stemmed from charge transfer between PDA and iridium polymer in the active layer (PDA-PPy3Ir) under an applied voltage.
A Fiber-Optic Sensor-Embedded and Machine Learning Assisted Smart Helmet for Multi-Variable Blunt Force Impact Sensing in Real Time
Authors: Zhuang Yiyang , Han Taihao , Yang Qingbo , O’Malley Ryan , Kumar Aditya , Gerald Rex E. , Huang Jie
Published: December 2022

Early on-site diagnosis of mild traumatic brain injury (mTBI) will provide the best guidance for clinical practice. However, existing methods and sensors cannot provide sufficiently detailed physical information related to the blunt force impact. In the present work, a smart helmet with a single embedded fiber Bragg grating (FBG) sensor is developed, which can monitor complex blunt force impact events in real time under both wired and wireless modes. The transient oscillatory signal “fingerprint” can specifically reflect the impact-caused physical deformation of the local helmet structure. By combination with machine learning algorithms, the unknown transient impact can be recognized quickly and accurately in terms of impact magnitude, direction, and latitude. Optimization of the training dataset was also validated, and the boosted ML models, such as the S-SVM+ and S-IBK+, are able to predict accurately with complex databases. Thus, the ML-FBG smart helmet system developed by this work may become a crucial intervention alternative during a traumatic brain injury event.
The Discourse Profile in Corticobasal Syndrome: A Comprehensive Clinical and Biomarker Approach
Authors: de Almeida Isabel Junqueira , Silagi Marcela Lima , Carthery-Goulart Maria Teresa , Parmera Jacy Bezerra , Cecchini Mario Amore , Coutinho Artur Martins , Dozzi Brucki Sonia Maria , Nitrini Ricardo , Schochat Eliane
Published: December 2022

The aim of this study was to characterize the oral discourse of CBS patients and to verify whether measures obtained during a semi-spontaneous speech production could differentiate CBS patients from controls. A second goal was to compare the performance of patients with CBS probably due to Alzheimer’s disease (CBS-AD) pathology and CBS not related to AD (CBS-non-AD) in the same measures, based on the brain metabolic status (FDG-PET) and in the presence of amyloid deposition (amyloid-PET). Results showed that CBS patients were significantly different from controls in speech rate, lexical level, informativeness, and syntactic complexity. Discursive measures did not differentiate CBS-AD from CBS-non-AD. However, CBS-AD displayed more lexical-semantic impairments than controls, a profile that is frequently reported in patients with clinical AD and the logopenic variant of primary progressive aphasia (lvPPA). CBS-non-AD presented mainly with impairments related to motor speech disorders and syntactic complexity, as seen in the non-fluent variant of PPA.