bluuebunny/crossref_metadata_2025 huggingface dataset:
Fucosterol Isolated from Dietary Brown Alga Sargassum horneri Protects TNF-α/IFN-γ-Stimulated Human Dermal Fibroblasts Via Regulating Nrf2/HO-1 and NF-κB/MAPK Pathways
Authors: Kirindage Kirinde Gedara Isuru Sandanuwan , Jayasinghe Arachchige Maheshika Kumari , Han Eui-Jeong , Jee Youngheun , Kim Hyun-Jin , Do Sun Gil , Fernando Ilekuttige Priyan Shanura , Ahn Ginnae
Published: July 2022

Sargassum horneri is a well-known edible brown alga that is widely abundant in the sea near China, Korea, and Japan and has a wide range of bioactive compounds. Fucosterol (FST), which is a renowned secondary metabolite in brown algae, was extracted from S. horneri to 70% ethanol, isolated via high-performance liquid chromatography (HPLC), followed by the immiscible liquid-liquid separation, and its structure was confirmed by NMR spectroscopy. The present study was undertaken to investigate the effects of FST against oxidative stress, inflammation, and its mechanism of action in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human dermal fibroblast (HDF). FST was biocompatible with HDF cells up to the 120 μM dosage. TNF-α/IFN-γ stimulation significantly decreased HDF viability by notably increasing reactive oxygen species (ROS) production. FST dose-dependently decreased the intracellular ROS production in HDFs. Western blot analysis confirmed a significant increment of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) involvement in FST-treated HDF cells. In addition, the downregulation of inflammatory mediators, molecules related to connective tissue degradation, and tissue inhibitors of metalloproteinases were identified. TNF-α/IFN-γ stimulation in HDF cells increased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) mediators, and its phosphorylation was reduced with the treatment of FST in a dose-dependent manner. Results obtained from western blot analysis of the NF-κB nuclear translocation were supported by immunocytochemistry results. Collectively, the outcomes suggested that FST significantly upregulates the Nrf2/HO-1 signaling and regulates NF-κB/MAPK signaling pathways to minimize the inflammatory responses in TNF-α/IFN-γ-stimulated HDF cells.
Cardioprotective Effect of Acetylsalicylic Acid in the Myocardial Ischemia-Reperfusion Model on Oxidative Stress Markers Levels in Heart Muscle and Serum
Authors: Frydrychowski Piotr , Michałek Marcin , Bil-Lula Iwona , Chełmecka Elżbieta , Kafel Alina , Noszczyk-Nowak Agnieszka , Stygar Dominika
Published: July 2022

Heart failure occurs in increased oxidative stress conditions, which contribute to the progression of pathological changes. Orally or intravenously administered acetylsalicylic acid (ASA, aspirin) is typically used in human patients with acute myocardial ischemia. The study used an experimental porcine ischemia-reperfusion model to evaluate the potential cardioprotective effect of intracoronary administered ASA on myocardial ischemia-reperfusion injury. The cardioprotective effect of ASA was evaluated by measuring selected oxidative stress markers levels in infarcted and non-infarcted myocardium 14 days after the procedure, and three times in serum, before the procedure, during the reperfusion process, and after 14-day recovery. The results showed that intracoronary administrated ASA reduced the oxidative stress. The level of oxidative stress, measured with the non-enzymatic markers total antioxidant capacity (TAC), total oxidative status (TOS), and malondialdehyde (MDA), and the enzymatic markers glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), in heart tissue was significantly higher in a control group injected with saline. The level of oxidative stress in serum, measured with TAC, TOS, oxidative stress index (OSI), and lipofuscin (LF), was also higher in the control group than in animals injected with ASA. The confirmed cardioprotective effect of intracoronary administered ASA provides the foundation for further studies on ASA intracoronary application, which may lead to the development of a new therapy for the treatment of ischemia-reperfusion complications in humans.
Sinularin Induces Oxidative Stress-Mediated Apoptosis and Mitochondrial Dysfunction, and Inhibits Angiogenesis in Glioblastoma Cells
Authors: Hsu Shih-Yuan , Wen Zhi-Hong , Shih Po-Chang , Kuo Hsiao-Mei , Lin Sung-Chun , Liu Hsin-Tzu , Lee Yi-Hsin , Wang Yi-Jen , Chen Wu-Fu , Chen Nan-Fu
Published: July 2022

Glioblastoma multiforme (GBM) is a cancer of largely unknown cause that leads to a 5-year survival rate of approximately 7% in the United States. Current treatment strategies are not effective, indicating a strong need for the development of novel therapies. In this study, the outcomes of sinularin, a marine-derived product, were evaluated against GBM. Our cellular studies using GBM cells revealed that sinularin induces cell death. The measured half maximal inhibitory concentrations (IC50) values ranged from 30 to 6 μM at 24–72 h. Cell death was induced via the generation of ROS leading to mitochondria-mediated apoptosis. This was evidenced by annexin V/propidium iodine staining and an upregulation of cleaved forms of the pro-apoptotic proteins caspase 9, 3, and PARP, and supported by CellROXTM Green, MitoSOXTM Red, and CM-H2DCFDA staining methods. In addition, we observed a downregulation of the antioxidant enzymes SOD1/2 and thioredoxin. Upon treatment with sinularin at the ~IC50 concentration, mitochondrial respiration capacities were significantly reduced, as shown by measuring the oxygen consumption rates and enzymatic complexes of oxidative phosphorylation. Intriguingly, sinularin significantly inhibited indicators of angiogenesis such as vessel tube formation, cell migration, and cell mobility in human umbilical vein endothelial cells or the fusion cell line EA.Hy926. Lastly, in a transgenic zebrafish model, intersegmental vessel formation was also significantly inhibited by sinularin treatment. These findings indicate that sinularin exerts anti-brain cancer properties that include apoptosis induction but also antiangiogenesis.
Conductive Gas Plasma Treatment Augments Tumor Toxicity of Ringer’s Lactate Solutions in a Model of Peritoneal Carcinomatosis
Authors: Miebach Lea , Freund Eric , Cecchini Alessandra , Bekeschus Sander
Published: July 2022

Reactive species generated by medical gas plasma technology can be enriched in liquids for use in oncology targeting disseminated malignancies, such as metastatic colorectal cancer. Notwithstanding, reactive species quantities depend on the treatment mode, and we recently showed gas plasma exposure in conductive modes to be superior for cancer tissue treatment. However, evidence is lacking that such a conductive mode also equips gas plasma-treated liquids to confer augmented intraperitoneal anticancer activity. To this end, employing atmospheric pressure argon plasma jet kINPen-treated Ringer’s lactate (oxRilac) in a CT26-model of colorectal peritoneal carcinomatosis, we tested repeated intraabdominal injection of such remotely or conductively oxidized liquid for antitumor control and immunomodulation. Enhanced reactive species formation in conductive mode correlated with reduced tumor burden in vivo, emphasizing the advantage of conduction over the free mode for plasma-conditioned liquids. Interestingly, the infiltration of lymphocytes into the tumors was equally enhanced by both treatments. However, significantly lower levels of interleukin (IL)4 and IL13 and increased levels of IL2 argue for a shift in intratumoral T-helper cell subpopulations correlating with disease control. In conclusion, our data argue for using conductively over remotely prepared plasma-treated liquids for anticancer treatment.
Vibration Fatigue Analysis of a Simply Supported Cracked Beam Subjected to a Typical Load
Authors: Ma Yijiang , Chen Guoping , Wu Jie , Ma Kangjia , Fan Le
Published: July 2022

In order to realize the accurate prediction of the vibration fatigue life of the beam in service, a loose coupling analysis method is proposed to carry out vibration fatigue analysis of a beam with an initial crack. In modal analysis, the initial crack segment is replaced with a torsion spring, and the damping loss factor is introduced by the complex modulus of elasticity; for the simply supported beam, the inherent vibration characteristic equation of the cracked beam is derived. In vibration fatigue analysis, the interaction between the crack’s growth and vibration analysis is considered, and a loose coupling analysis method is proposed to conduct modal dynamic response and vibration fatigue analysis simultaneously. Results indicate that the crack’s relative location and depth determine the modal of the cracked beam, and crack parameters, damping loss factor and external excitation frequency are important factors for the vibration fatigue life of the beam.
Multi-Mode Compact Microscopy for High-Contrast and High-Resolution Imaging
Authors: Kim Kisoo , Hwang Yeon , Park Jongbok
Published: July 2022

We report a multi-mode compact microscope (MCM) for high-contrast and high-resolution imaging. The MCM consists of two LED illuminations, a magnification lens, a lift stage, and a housing with image processing and LED control boards. The MCM allows multi-modal imaging, including reflection, transmission, and higher magnification modes. The dual illuminations also provide high-contrast imaging of various targets such as biological samples and microcircuits. The high dynamic range (HDR) imaging reconstruction of MCM increases the dynamic range of the acquired images by 1.36 times. The microlens array (MLA)-assisted MCM also improves image resolution through the magnified virtual image of MLA. The MLA-assisted MCM successfully provides a clear, magnified image by integrating a pinhole mask to prevent image overlap without additional alignment. The magnification of MLA-assisted MCM was increased by 3.92 times compared with that of MCM, and the higher magnification mode demonstrates the image resolution of 2.46 μm. The compact portable microscope can provide a new platform for defect inspection or disease detection on site.
Motion Deblurring for Single-Pixel Spatial Frequency Domain Imaging
Authors: Dan Mai , Liu Meihui , Gao Feng
Published: July 2022

The single-pixel imaging technique is applied to spatial frequency domain imaging (SFDI) to bring significant performance advantages in band extension and sensitivity enhancement. However, the large number of samplings required can cause severe quality degradations in the measured image when imaging a moving target. This work presents a novel method of motion deblurring for single-pixel SFDI. In this method, the Fourier coefficients of the reflected image are measured by the Fourier single-pixel imaging technique. On this basis, a motion-degradation-model-based compensation, which is derived by the phase-shift and frequency-shift properties of Fourier transform, is adopted to eliminate the effects of target displacements on the measurements. The target displacements required in the method are obtained using a fast motion estimation approach. A series of numerical and experimental validations show that the proposed method can effectively deblur the moving targets and accordingly improves the accuracy of the extracted optical properties, rendering it a potentially powerful way of broadening the clinical application of single-pixel SFDI.
The Protection of Data Sharing for Privacy in Financial Vision
Authors: Wang Yi-Ren , Tsai Yun-Cheng
Published: July 2022

The primary motivation is to address difficulties in data interpretation or a reduction in model accuracy. Although differential privacy can provide data privacy guarantees, it also creates problems. Thus, we need to consider the noise setting for differential privacy is currently inconclusive. This paper’s main contribution is finding a balance between privacy and accuracy. The training data of deep learning models may contain private or sensitive corporate information. These may be dangerous to attacks, leading to privacy data leakage for data sharing. Many strategies are for privacy protection, and differential privacy is the most widely applied one. Google proposed a federated learning technology to solve the problem of data silos in 2016. The technology can share information without exchanging original data and has made significant progress in the medical field. However, there is still the risk of data leakage in federated learning; thus, many models are now used with differential privacy mechanisms to minimize the risk. The data in the financial field are similar to medical data, which contains a substantial amount of personal data. The leakage may cause uncontrollable consequences, making data exchange and sharing difficult. Let us suppose that differential privacy applies to the financial field. Financial institutions can provide customers with higher value and personalized services and automate credit scoring and risk management. Unfortunately, the economic area rarely applies differential privacy and attains no consensus on parameter settings. This study compares data security with non-private and differential privacy financial visual models. The paper finds a balance between privacy protection with model accuracy. The results show that when the privacy loss parameter ϵ is between 12.62 and 5.41, the privacy models can protect training data, and the accuracy does not decrease too much.
Strain Relaxation Effect on the Peak Wavelength of Blue InGaN/GaN Multi-Quantum Well Micro-LEDs
Authors: Zhang Chaoqiang , Gao Ke , Wang Fei , Chen Zhiming , Shields Philip , Lee Sean , Wang Yanqin , Zhang Dongyan , Liu Hongwei , Niu Pingjuan
Published: July 2022

In this paper, the edge strain relaxation of InGaN/GaN MQW micro-pillars is studied. Micro-pillar arrays with a diameter of 3–20 μm were prepared on a blue GaN LED wafer by inductively coupled plasma (ICP) etching. The peak wavelength shift caused by edge strain relaxation was tested using micro-LED pillar array room temperature photoluminescence (PL) spectrum measurements. The results show that there is a nearly 3 nm peak wavelength shift between the micro-pillar arrays, caused by a high range of the strain relaxation region in the small size LED pillar. Furthermore, a 19 μm micro-LED pillar’s Raman spectrum was employed to observe the pillar strain relaxation. It was found that the Raman E2H mode at the edge of the micro-LED pillar moved to high frequency, which verified an edge strain relaxation of = 0.1%. Then, the exact strain and peak wavelength distribution of the InGaN quantum wells were simulated by the finite element method, which provides effective verification of our PL and Raman strain relaxation analysis. The results and methods in this paper provide good references for the design and analysis of small-size micro-LED devices.
Evolutionary Algorithm with Deep Auto Encoder Network Based Website Phishing Detection and Classification
Authors: Alqahtani Hamed , Alotaibi Saud S. , Alrayes Fatma S. , Al-Turaiki Isra , Alissa Khalid A. , Aziz Amira Sayed A. , Maray Mohammed , Al Duhayyim Mesfer
Published: July 2022

Website phishing is a cyberattack that targets online users for stealing their sensitive data containing login credential and banking details. The phishing websites appear very similar to their equivalent legitimate websites for attracting a huge amount of Internet users. The attacker fools the user by offering the masked webpage as legitimate or reliable for retrieving its important information. Presently, anti-phishing approaches necessitate experts to extract phishing site features and utilize third-party services for phishing website detection. These techniques have some drawbacks, as the requirement of experts for extracting phishing features is time consuming. Many solutions for phishing websites attack have been presented, such as blacklist or whitelist, heuristics, and machine learning (ML) based approaches, which face difficulty in accomplishing effectual recognition performance due to the continual improvements of phishing technologies. Therefore, this study presents an optimal deep autoencoder network based website phishing detection and classification (ODAE-WPDC) model. The proposed ODAE-WPDC model applies input data pre-processing at the initial stage to get rid of missing values in the dataset. Then, feature extraction and artificial algae algorithm (AAA) based feature selection (FS) are utilized. The DAE model with the received features carried out the classification process, and the parameter tuning of the DAE technique was performed using the invasive weed optimization (IWO) algorithm to accomplish enhanced performance. The performance validation of the ODAE-WPDC technique was tested using the Phishing URL dataset from the Kaggle repository. The experimental findings confirm the better performance of the ODAE-WPDC model with maximum accuracy of 99.28%.
New Type of Degenerate Changhee–Genocchi Polynomials
Authors: Alatawi Maryam Salem , Khan Waseem Ahmad
Published: July 2022

A remarkably large number of polynomials and their extensions have been presented and studied. In this paper, we consider a new type of degenerate Changhee–Genocchi numbers and polynomials which are different from those previously introduced by Kim. We investigate some properties of these numbers and polynomials. We also introduce a higher-order new type of degenerate Changhee–Genocchi numbers and polynomials which can be represented in terms of the degenerate logarithm function. Finally, we derive their summation formulae.
Soccer Scoring Techniques—A Biomechanical Re-Conception of Time and Space for Innovations in Soccer Research and Coaching
Authors: Shan Gongbing , Zhang Xiang
Published: July 2022

Background: Scientifically, both temporal and spatial variables must be examined when developing programs for training various soccer scoring techniques (SSTs). Unfortunately, previous studies on soccer goals have overwhelmingly focused on the development of goal-scoring opportunities or game analysis in elite soccer, leaving the consideration of player-centered temporal-spatial aspects of SSTs mostly neglected. Consequently, there is a scientific gap in the current scoring-opportunity identification and a dearth of scientific concepts for developing SST training in elite soccer. Objectives: This study aims to bridge the gap by introducing effective/proprioceptive shooting volume and a temporal aspect linked to this volume. Method: the SSTs found in FIFA Puskás Award (132 nominated goals between 2009 and 2021) were quantified by using biomechanical modeling and anthropometry. Results: This study found that players’ effective/proprioceptive shooting volume could be sevenfold that of normal practice in current coaching. Conclusion: The overlooked SSTs in research and training practice are commonly airborne and/or acrobatic, which are perceived as high-risk and low-reward. Relying on athletes’ talent to improvise on these complex skills can hardly be considered a viable learning/training strategy. Future research should focus on developing player-centered temporal-spatial SST training to help demystify the effectiveness of proprioceptive shooting volume and increase scoring opportunities in soccer.
CT-Derived 3D Printing for Coronary Artery Cannulation Simulator Design Manufacturing
Authors: Etami Helvina Vika , Rismawanti Rochmi Isnaini , Hanifah Vita Arfiana Nur , Herianto Herianto , Yanuar Yarabisa , Kuswanto Djoko , Anggrahini Dyah Wulan , Gharini Putrika Prastuti Ratna
Published: July 2022

Mastering coronary angiography requires practice. Cadavers and animals do not accurately represent the human anatomical body, and practicing with actual patients has medical safety issues. Simulation offers safe and realistic conditions for cardiology intervention training. In this study, we propose a novel 3D printed simulator that contains physically realistic anatomy and has four access points. It increases safety for patients and students, and production is low-cost. We aimed to make and validate this simulator design as a prototype for coronary cannulation training. It was designed using computed tomography (CT) scan data of aorta, coronary, and heart models, and was printed by 3D printing with resin materials consisting of 75% or 85% clear resin and 25% or 15% flexible resin additive. The simulator was constructed with a camera above the simulator with a degree of LAO of 30°/0°, a display table, and an acrylic box. Twelve validators were interviewed for their expert opinions and analyzed by a qualitative method. They scored the simulator’s suitability on a four-point Likert scale questionnaire. They described the simulator as having admirable values for all aspects (85.8%), curriculum suitability (92%), educational importance (94%), accuracy (83%), efficiency (78%), safety (87.5%), endurance (81.2%), aesthetics (80.7%), storage (85.4%), and affordability (85.8%).
Cognitive Difficulties, Psychological Symptoms, and Long Lasting Somatic Complaints in Adolescents with Previous SARS-CoV-2 Infection: A Telehealth Cross-Sectional Pilot Study
Authors: Tarantino Samuela , Graziano Sonia , Carducci Chiara , Giampaolo Rosaria , Grimaldi Capitello Teresa
Published: July 2022

Background. Few studies have evaluated cognitive functioning and mental health in children and adolescents who contracted the SARS-CoV-2 infection. We investigated the prevalence and association of neuropsychological difficulties, psychological symptoms, and self-reported long-COVID complaints in a sample of adolescents. Methods. Thirty-one adolescents infected by COVID-19 within 3–6 months prior to the assessment were included. Neuropsychological difficulties, psychological symptoms, and self-reported long-COVID complaints were evaluated using a checklist and a battery of multiple standardized measures, using a telehealth procedure. Symptoms during the infection were also detected. Results. We included 31 adolescents (23 girls, 8 boys; mean age 14.1, SD = 2). We found borderline scores in 32.3% and 45.2% of our sample for phonemic and category fluency, respectively. A high percentage of participants showed symptoms of depression (80.6%) and anxiety (61.3%). Fifty-eight percent reported at least one long-COVID symptom. The most common symptoms were headache and attention problems (58%). Subjects presenting numbness/weakness, fatigue, brain fog, or attention problems had higher scores in depression, anxiety, and post-traumatic stress symptoms (p ≤ 0.05). Conclusion. This is a pilot study limited by the lack of control group. However, we found that cognitive, psychological, and physical symptoms were very common among adolescents recovered from COVID-19.
Interhemispheric Facilitatory Effect of High-Frequency rTMS: Perspective from Intracortical Facilitation and Inhibition
Authors: Tian Dongting , Izumi Shin-Ichi
Published: July 2022

The activity of excitatory and inhibitory neural circuits in the motor cortex can be probed and modified by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), noninvasively. At present, not only has a consensus regarding the interhemispheric effect of high frequency rTMS not been reached, but the attributes of these TMS-related circuits are also poorly understood. To address this question comprehensively, we integrated a single- and paired-pulse TMS evaluation with excitatory 20-Hz rTMS intervention in order to probe the interhemispheric effect on the intracortical circuits by high-frequency rTMS. In the rest state, after 20-Hz rTMS, a significant increase of single-pulse MEP and paired-pulse intracortical facilitation (ICF) in the non-stimulated hemisphere was observed with good test–retest reliability. Intracortical inhibition (measured by the cortical silent period) in the unstimulated hemisphere also increased after rTMS. No significant time–course change was observed in the sham-rTMS group. The results provide the evidence that 20-Hz rTMS induced a reliable interhemispheric facilitatory effect. Findings from the present study suggest that the glutamatergic facilitatory system and the GABAergic inhibitory system may vary synchronously.
CysLT2R Antagonist HAMI 3379 Ameliorates Post-Stroke Depression through NLRP3 Inflammasome/Pyroptosis Pathway in Gerbils
Authors: Zhou Li , Zhang Jiajia , Han Xue , Fang Jie , Zhou Shasang , Lu Lingqun , Shi Qiaojuan , Ying Huazhong
Published: July 2022

Post-stroke depression (PSD) is a kind of prevalent emotional disorder following stroke that usually results in slow functional recovery and even increased mortality. We had reported that the cysteinyl leukotriene receptor 2 (CysLT2R) antagonist HAMI3379 (HM3379) contributes to the improvement of neurological injury. The present study was designed to investigate the role of HM3379 in PSD-induced chronic neuroinflammation and related mechanisms in gerbils. The gerbils were subjected to transient global cerebral ischemia (tGCI) and spatial restraint stress to induce the PSD model. They were randomized to receive the vehicle or HM3379 (0.1 mg/kg, i.p.) for a consecutive 14 days. In the PSD-treated gerbils, HM3379 had noteworthy efficacy in improving the modified neurological severity score (mNSS) and depression-like behaviors, including the sucrose preference test and the forced swim test. HM3379 administration significantly mitigated neuron loss, lessened TUNEL-positive neurons, and reduced the activation of microglia in the cerebral cortex. Importantly, HM3379 downregulated protein expressions of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis including NLRP3, cleaved caspase-1, interleukin-1β (IL-1β), IL-18, cleaved gasdermin-N domain (GSDMD-N), and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC). Mechanistically, HM3379 could repress pyroptosis via inhibiting NLRP3 inflammasome activation under oxygen-glucose deprivation (OGD) stimulation. Knockdown of CysLT2R by short hairpin RNA (shRNA) or overexpression of CysLT2R by lentivirus (LV)-CysLT2R could abolish or restore the anti-depression effect of HM3379. Our results demonstrated that the selective CysLT2R antagonist HM3379 has beneficial effects on PSD, partially by suppressing the NLRP3 inflammasome/pyroptosis pathway.
EEG-Based Emotion Classification Using Improved Cross-Connected Convolutional Neural Network
Authors: Dai Jinxiao , Xi Xugang , Li Ge , Wang Ting
Published: July 2022

The use of electroencephalography to recognize human emotions is a key technology for advancing human–computer interactions. This study proposes an improved deep convolutional neural network model for emotion classification using a non-end-to-end training method that combines bottom-, middle-, and top-layer convolution features. Four sets of experiments using 4500 samples were conducted to verify model performance. Simultaneously, feature visualization technology was used to extract the three-layer features obtained by the model, and a scatterplot analysis was performed. The proposed model achieved a very high accuracy of 93.7%, and the extracted features exhibited the best separability among the tested models. We found that adding redundant layers did not improve model performance, and removing the data of specific channels did not significantly reduce the classification effect of the model. These results indicate that the proposed model allows for emotion recognition with a higher accuracy and speed than the previously reported models. We believe that our approach can be implemented in various applications that require the quick and accurate identification of human emotions.
Association between Deep Medullary Veins in the Unaffected Hemisphere and Functional Outcome in Acute Cardioembolic Stroke: An Observational Retrospective Study
Authors: Ye Chen , Liu Junfeng , Wei Chenchen , Wang Yanan , Song Quhong , Pan Ruosu , Tao Wendan , Wu Bo , Liu Ming
Published: July 2022

Objective: To explore whether deep medullary veins (DMVs) in the unaffected hemisphere were associated with functional outcome in acute cardioembolic stroke patients. Methods: Acute cardioembolic stroke patients at a single center were retrospectively included. DMVs visibility in the unaffected hemisphere was assessed using a well-established four-grade scoring method based on susceptibility-weighted imaging (SWI): grades 0–3 (grade 0 for no visible DMVs; grade 1 for the numbers of conspicuous DMVs < 5; grade 2 for numbers raging from 5 to 10; grade 3 for more than 10). Patients were further divided into mild-to-moderate (grade 0–2) and severe DMVs (grade 3) groups. Functional outcomes were evaluated using the modified Rankin scale (mRS) score at three months. Poor outcome was defined as mRS ≥ 3. Binary logistic regression analysis was used to explore the association between DMVs grade and functional outcome. Results: A total of 170 patients were finally included. Compared with the mild-to-moderate DMVs group (149 patients), the severe DMVs group (21 patients) had higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.002), lower levels of admission systolic blood pressure (BP) (p = 0.031), and elevated rates of large infarction (p = 0.003). At three months, the severe DMVs group had higher mRS (p = 0.002). Patients in the poor outcome group (82/170, 48.2%) had older age, higher baseline NIHSS score, lower admission diastolic BP, higher rates of hemorrhagic transformation and large infarction, and an increased proportion of severe DMVs (all p < 0.05). After adjusting for confounders, multivariable regression analysis showed that the severe DMVs grade (adjusted odds ratio [OR] = 5.830, 95% confidence interval [CI] = 1.266–26.856, p = 0.024) was significantly associated with three-month functional outcomes without interaction with other potential risk factors (p for interaction > 0.05). Conclusions: DMVs grade in the unaffected hemisphere was independently associated with three-month functional outcome in acute cardioembolic stroke patients. Patients with severe DMVs were more likely to have a poor functional outcome at three months.
Molecular Profiles of Serum-Derived Extracellular Vesicles in High-Grade Serous Ovarian Cancer
Authors: Zhao Li , Corvigno Sara , Ma Shaolin , Celestino Joseph , Fleming Nicole D. , Hajek Richard A. , Lankenau Ahumada Adrian , Jennings Nicholas B. , Thompson Erika J. , Tang Hongli , Westin Shannon N. , Jazaeri Amir A. , Zhang Jianhua , Futreal P. Andrew , Sood Anil K. , Lee Sanghoon
Published: July 2022

Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified distinct somatic EV-DNA alterations in cancer-hallmark genes and in ovarian cancer genes, as well as significantly altered oncogenic pathways between the R0 group and NACT groups. We also found significantly altered EV-RNA transcriptomic variations and enriched pathways between the groups. Taken together, our data suggest that the molecular characteristics of EVs could enable prediction of patients with HGSC who could undergo R0 surgery or respond to chemotherapy.
Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2
Authors: Wang Zitong , Chen Yingying , Li Xiaoyu , Zhang Yuhan , Zhao Xiaokun , Zhou Hao , Lu Xuebo , Zhao Lili , Yuan Qiang , Shi Yunshu , Zhao Jimin , Dong Ziming , Jiang Yanan , Liu Kangdong
Published: July 2022

Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2.
The Diagnostic Value of the Added MR Imaging of the Scrotum in the Preoperative Workup of Sonographically Indeterminate Testicular Lesions—A Retrospective Multicenter Analysis
Authors: Deininger Susanne , Lusuardi Lukas , Pallauf Maximilian , Hecht Stefan , Forstner Rosemarie , Meissnitzer Matthias , Distler Florian A. , Erne Eva , Graf Sebastian , Lenart Sebastian , Putz Juliane , Deininger Christian , Törzsök Peter
Published: July 2022

Background: The purpose of this study was to retrospectively analyze the diagnostic accuracy of magnetic resonance imaging (MRI) examinations of the scrotum in comparison with standard ultrasound (US) and histopathology. Methods: A retrospective multi-center analysis of MRI examinations of the scrotum performed between 06/2008 and 04/2021 was conducted. Results: A total of n = 113 patients were included. A total of 53 histopathologies were available, with 52.8% malignant and 50.9% benign findings. Related to histopathology, imaging was true negative, false negative, false positive, and true positive in 4.1%, 2.1%, 25.0% and 37.5% for standard ultrasound (US) and 9.1%, 1.8%, 25.5% and 43.6% for MRI. Sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 20.0%, 36.0% and 88.9% for US and 85.7%, 72.8%, 52.1% and 93.7% for MRI, respectively. Benign lesions were significantly smaller than malignant ones in standard US (p = 0.001), histopathology (p = 0.001) and MRI (p = 0.004). The size of malignant tumors did not differ significantly between histopathology and standard US (0.72) and between histopathology and MRI (p = 0.88). Conclusions: MRI shows good sensitivity and specificity for the estimation of testicular tumors in this collective. Benign lesions are significantly smaller than malignant ones. Both MRI and US can estimate the size of malignant tumors adequately.
The Association between Blood Indexes and Immune Cell Concentrations in the Primary Tumor Microenvironment Predicting Survival of Immunotherapy in Gastric Cancer
Authors: Yuan Jiajia , Zhao Xingwang , Li Yanyan , Yao Qian , Jiang Lei , Feng Xujiao , Shen Lin , Li Yilin , Chen Yang
Published: July 2022

The tumor microenvironment plays a vital role in tumor progression and treatment response. However, the association between immune cell concentrations in primary tumor and blood indexes remains unknown. Thus, we enrolled patients with gastric cancer (GC) in two cohorts. We used multiplexed immunohistochemistry to quantify in situ proteins covering rare cell types at sub-cellular resolution in 80 patients with GC in the first cohort. A high correlation between the LMR (lymphocyte-to-monocyte ratio)/NLR (neutrophil-to-lymphocyte ratio) and tumor immune microenvironment was found. The density of exhausted CD8 T cells including CD8+PD1−TIM3+, CD8+LAG3+PD1+, CD8+LAG3+PD1−, CD8+LAG3+PD1+TIM3− was negatively associated with LMR and positively associated with NLR (p < 0.05). Additionally, the higher density of macrophages in tumor core was associated with a higher platelet-to-lymphocyte ratio and systemic immune-inflammation index. Furthermore, we validated the prognostic value of LMR and NLR in an independent cohort of 357 gastric cancer patients receiving immunotherapy. Higher LMR at baseline was significantly associated with superior immune-related PFS (irPFS) and a trend of superior immune-related OS (irOS). Higher NLR was associated with inferior irOS. In conclusion, blood indexes were associated with immune cells infiltrating in primary tumors of GC. NLR and LMR are associated with the density of exhausted CD8+ T immune cells, which leads to prognostic values of immunotherapy.
SLC35A2 Deficiency Promotes an Epithelial-to-Mesenchymal Transition-like Phenotype in Madin–Darby Canine Kidney Cells
Authors: Kot Magdalena , Mazurkiewicz Ewa , Wiktor Maciej , Wiertelak Wojciech , Mazur Antonina Joanna , Rahalevich Andrei , Olczak Mariusz , Maszczak-Seneczko Dorota
Published: July 2022

In mammalian cells, SLC35A2 delivers UDP–galactose for galactosylation reactions that take place predominantly in the Golgi lumen. Mutations in the corresponding gene cause a subtype of a congenital disorder of glycosylation (SLC35A2-CDG). Although more and more patients are diagnosed with SLC35A2-CDG, the link between defective galactosylation and disease symptoms is not fully understood. According to a number of reports, impaired glycosylation may trigger the process of epithelial-to-mesenchymal transition (EMT). We therefore examined whether the loss of SLC35A2 activity would promote EMT in a non-malignant epithelial cell line. For this purpose, we knocked out the SLC35A2 gene in Madin–Darby canine kidney (MDCK) cells. The resulting clones adopted an elongated, spindle-shaped morphology and showed impaired cell–cell adhesion. Using qPCR and western blotting, we revealed down-regulation of E-cadherin in the knockouts, while the fibronectin and vimentin levels were elevated. Moreover, the knockout cells displayed reorganization of vimentin intermediate filaments and altered subcellular distribution of a vimentin-binding protein, formiminotransferase cyclodeaminase (FTCD). Furthermore, depletion of SLC35A2 triggered Golgi compaction. Finally, the SLC35A2 knockouts displayed increased motility and invasiveness. In conclusion, SLC35A2-deficient MDCK cells showed several hallmarks of EMT. Our findings point to a novel role for SLC35A2 as a gatekeeper of the epithelial phenotype.
Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations
Authors: Eslabão Lívia Budziarek , Gubert Gabriela Farias , Beltrame Lucas Cafferati , Mello Isis M. A. , Bruna-Romero Oscar , Zárate-Bladés Carlos R.
Published: July 2022

Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of a reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic-resistant bacteria. Moreover, the impact of using this wide-spectrum antibiotic on gut microbiota in a critical period of development, and weakness is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein–energy undernutrition (PEU) in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing, we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND + SXT). We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in a significant loss in community richness and beta diversity. Furthermore, we identified the reduction of three genera in SXT treated mice, including the butyrate producers Faecalibacterium and Anaerotruncus. Both UND and double challenge (UND + SXT) resulted in a reduction of the amino acid’s biosynthesis pathway related to cell growth. Our results show that the SXT prophylaxis of young mice during an undernourishment period did not re-establish the undernourished microbiota community composition similar to healthy controls but induced a distinct dysbiotic profile with functional metabolic consequences.
Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer: Analysis of the Tumor Immune Microenvironment and Risk Profiles
Authors: Sajjadi Elham , Venetis Konstantinos , Noale Marianna , Azim Hatem A. , Blundo Concetta , Bonizzi Giuseppina , Di Loreto Eugenia , Scarfone Giovanna , Ferrero Stefano , Maggi Stefania , Barberis Massimo , Veronesi Paolo , Galimberti Viviana E. , Viale Giuseppe , Fusco Nicola , Peccatori Fedro A. , Guerini-Rocco Elena
Published: July 2022

Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early-onset breast cancer (EOBC) in non-pregnant women. A total of 83 PrBC and 89 EOBC were selected from our Institutional registry and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A significantly lower frequency of hormone receptor (HR)-positive tumors was observed in PrBC. The prevalence of low/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+/HER2– breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. Moreover, the death rate was higher in PrBC with CD8+ TILs. The TME of PrBC is characterized by specific patterns of TIL subpopulations with significant biological and prognostic roles. Routine assessment of TILs and TILs subtyping in these patients would be a valid addition to the pathology report that might help identify clinically relevant subsets of women with PrBC.
Dissolved Gas Analysis in Transformer Oil Using Ni Catalyst Decorated PtSe2 Monolayer: A DFT Study
Authors: Wang Zengting , Zhang Guozhi , Liu Li , Wu Yunjian , Wang Jincong , Xiao Song
Published: July 2022

In this paper, the first-principles theory is used to explore the adsorption behavior of Ni catalyst decorated PtSe2 (Ni-PtSe2) monolayer toward the dissolved gas in transformer oil, namely CO and C2H2. Some Ni atoms from the catalyst are trapped in the Se vacancy on the pure PtSe2 surface. The geometry configurations of Ni-PtSe2 monolayer before and after gas adsorption, the electronic property of Ni-PtSe2 monolayer upon gas adsorption, and the sensibility and recovery property of Ni-PtSe2 monolayer are explored in this theoretical work. Through the simulation, the Ead of CO and C2H2 gas adsorption systems are calculated as −1.583 eV and −1.319 eV, respectively, both identified as chemisorption and implying the stronger performance of the Ni-PtSe2 monolayer on CO molecule, which is further supported by the DOS and BS analysis. According to the formula, the sensitivity of Ni-PtSe2 monolayer towards CO and C2H2 detection can reach up to 96.74% and 99.91% at room temperature (298 K), respectively, which manifests the favorable sensing property of these gases as a chemical resistance-type sensor. Recovery behavior indicates that the Ni-PtSe2 monolayer is a satisfied gas scavenger upon the noxious gas dissolved in transformer oil, but its recovery time at room temperature is not satisfactory. To sum up, we monitor the status of the transformer to guarantee the stable operation of the power system through the Ni-PtSe2 monolayer upon the detection of CO and C2H2, which may realize related applications, and provide the basis and reference to cutting-edge research in the field of electricity in the future.
Three-Dimensional Printing Technology in Orthodontics for Dental Models: A Systematic Review
Authors: Tsolakis Ioannis A. , Gizani Sotiria , Panayi Nearchos , Antonopoulos Georgios , Tsolakis Apostolos I.
Published: July 2022

Background: Three-dimensional printing technology is an additive manufacturing technology that is used to reconstruct 3D objects. In the last decade, it has been rapidly involved in dentistry and in orthodontics. This article aims to review the literature and present the accuracy of different 3D printer types and any factors that could affect the 3D printing of dental models in the orthodontic field. Methods: The search strategy of this systematic review included keywords in combination with MeSH terms in Medline, Scopus, and Cochrane Library until June 2022 and only in English. Results: Eleven articles were selected for our study. All the articles were in vitro prospective studies, and they presented a low risk of bias. The results suggested that the accuracy of a printed dental cast can be affected by the different types of 3D technologies, the dental cast’s base design, and the printing materials. The accuracy appears to not be affected by the layer height and the position of the model on the building template. Conclusions: According to this systematic review, all different types of 3D technology can produce clinically accepted results for orthodontic purposes. There is a need for more studies to clarify the accuracy and added value of 3D printing technology in orthodontics.
TITF1 Screening in Human Congenital Diaphragmatic Hernia (CDH)
Authors: Gulino Maria Eugenia , Martucciello Giuseppe , Biffali Elio , Morbini Patrizia , Patti Roberta , Borra Marco , Scuderi Maria Grazia
Published: July 2022

TITF1 (Thyroid Transcription Factor-1) is a homeodomain-containing transcription factor. Previous studies showed that Titf1 null mice are characterized by failure of tracheo-oesophageal separation and impaired lung morphogenesis resulting in Pulmonary Hypoplasia (PH). In this study, we aim to evaluate the role of TITF1 in the pathogenesis of congenital diaphragmatic hernia (CDH) in humans. We investigated TITF1 expression in human trachea and lungs and performed direct mutation analysis in a CDH population. We studied 13 human fetuses at 14 to 24 weeks of gestation. Five μm sections were fixed in paraformaldehyde and incubated with anti-TITF1 primary antibody. Positive staining was visualized by biotinylated secondary antibody. We also performed TITF1 screening on genomic DNA extracted from peripheral blood of 16 patients affected by CDH and different degrees of PH, searching for mutations, insertions, and/or deletions, by sequencing the exonic regions of the gene. Histochemical studies showed positive brown staining of fetal follicular thyroid epithelium, normal fetal trachea, and normal fetal lung bronchial epithelium. Fetal esophageal wall was immunohistochemically negative. Molecular genetic analysis showed complete identity between the sequences obtained and the Wild Type (WT) form of the gene in all cases. No mutation, insertion and/or deletion was detected. Although TITF1 is expressed in the human fetal lung and has been considered to have a role in the pathogenesis of PH in CDH, the results of our study do not support the hypothesis that TITF1 mutations play a key role in the etiopathogenesis of CDH.