bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact Time Control Cooperative Guidance Law Design Based on Modified Proportional Navigation
Authors: Jiang Zhanyuan , Ge Jianquan , Xu Qiangqiang , Yang Tao
Published: August 2021

The paper proposes a two-dimensional impact time control cooperative guidance law under constant velocity and a three-dimensional impact time control cooperative guidance law under time-varying velocity, which can both improve the penetration ability and combat effectiveness of multi-missile systems and adapt to the complex and variable future warfare. First, a more accurate time-to-go estimation method is proposed, and based on which a modified proportional navigational guidance (MPNG) law with impact time constraint is designed in this paper, which is also effective when the initial leading angle is zero. Second, adopting cooperative guidance architecture with centralized coordination, using the MPNG law as the local guidance, and the desired impact time as the coordination variables, a two-dimensional impact time control cooperative guidance law under constant velocity is designed. Finally, a method of solving the expression of velocity is derived, and the analytic function of velocity with respect to time is given, a three-dimensional impact time control cooperative guidance law under time-varying velocity based on desired impact time is designed. Numerical simulation results verify the feasibility and applicability of the methods.
Temperament Predicts the Quality of Social Interactions in Captive Female Rhesus Macaques (Macaca mulatta)
Authors: Pomerantz Ori , Capitanio John P.
Published: August 2021

Previous reports suggest that female macaques with greater similarity in emotionality and nervous temperament, as evaluated in a well-established BioBehavioral Assessment (BBA) at the California National Primate Research Center, were more likely to form successful pairs. We tested whether the same measures can also predict the quality of social interactions among 20 female rhesus macaque pairs. We correlated the pairs’ emotionality and nervous temperament scores obtained in infancy and the levels of behaviors recorded systematically during the pairing process years later. Supporting previous findings, partners with similar emotionality scores were more affiliative, and pairs with similar nervous temperament expressed less dominance/submissive behavior. Exploratorily, we found that pairs that were better at processing social information (part of BBA) were also more anxious. Such animals should be prioritized to be introduced in rooms that house calmer, less aggressive animals and provide opportunities for hiding to alleviate their anxiety. Indeed, positive social experiences not only promote animal welfare, but also reduce stress related confounds and unexplained data variability. Therefore, by incorporating the animals’ temperament into the pair configuration process we increase the likelihood of forming high-quality pairs, both in terms of welfare and the research of which they are a part.
Microbiological Contamination Assessment in Higher Education Institutes
Authors: Viegas Carla , Pimenta Raquel , Dias Marta , Gomes Bianca , Brito Miguel , Aranha Caetano Liliana , Carolino Elisabete , Gomes Anita Quintal
Published: August 2021

The higher education sector represents a unique environment and it acts as a work environment, a learning environment for students, and frequently, also a home environment. The aim of this study was to determine the microbial contamination (SARS-CoV-2, fungi, and bacteria) in Higher Education Facilities (HEI) by using active and passive sampling methods and combining culture-based methods with molecular tools targeting Aspergillus section Fumigati. In addition, the resistance to azole profile was also assessed. Surface samples showed a range of total bacterial contamination between 1 × 103 to 3.1 × 106 CFU·m−2, while Gram-negative bacteria ranged from 0 to 1.9 × 104 CFU·m−2. Fungal contamination ranged from 2 × 103 to 1.8 × 105 CFU·m−2 on MEA, and from 5 × 103 to 1.7 × 105 CFU·m−2 on DG18. The most prevalent species found on both media was Cladosporium sp. (47.36% MEA; 32.33% DG18). Aspergillus genera was observed on MEA (3.21%) and DG18 (14.66%), but not in the supplemented media used for the azole screening. Aspergillus section Fumigati was detected in 2 air samples (2.22%, 2 out of 90 samples) by qPCR. When testing for SARS-CoV-2 all results were negative. The present study showed that although cleaning and disinfection procedures are done regularly due to the COVID-19 pandemic, being effective in eliminating SARS-CoV-2, surfaces were often contaminated with microorganisms other than SARS-CoV-2. This can be a result of increasing resistance to biocides, and to the wide range of environmental factors that can contribute to the dissemination of microbial contamination indoors.
Existence of Interhemispheric Inhibition between Foot Sections of Human Primary Motor Cortices: Evidence from Negative Blood Oxygenation-Level Dependent Signal
Authors: Naito Eiichi , Morita Tomoyo , Kimura Nodoka , Asada Minoru
Published: August 2021

Interhemispheric inhibition (IHI) between the left and right primary motor cortices (M1) plays an important role when people perform an isolated unilateral limb movement. Moreover, negative blood oxygenation-level dependent signal (deactivation) obtained from the M1 ipsilateral to the limb could be a surrogate IHI marker. Studies have reported deactivation in the hand section of the ipsilateral M1 during simple unilateral hand movement. However, deactivation in the foot section during unilateral foot movement has not been reported. Therefore, IHI between the foot sections of the bilateral M1s has been considered very weak or absent. Thirty-seven healthy adults performed active control of the right foot and also passively received vibration to the tendon of the tibialis anterior muscle of the right foot, which activates the foot section of the contralateral M1, with brain activity being examined through functional magnetic resonance imaging. The vibration and active tasks significantly and non-significantly, respectively, deactivated the foot section of the ipsilateral M1, with a corresponding 86% and 60% of the participants showing decreased activity. Thus, there could be IHI between the foot sections of the bilateral M1s. Further, our findings demonstrate between-task differences and similarities in cross-somatotopic deactivation.
The Effect of Light Sedation with Midazolam on Functional Connectivity of the Dorsal Attention Network
Authors: Wang Junkai , Xu Yachao , Deshpande Gopikrishna , Li Kuncheng , Sun Pei , Liang Peipeng
Published: August 2021

Altered connectivity within and between the resting-state networks (RSNs) brought about by anesthetics that induce altered consciousness remains incompletely understood. It is known that the dorsal attention network (DAN) and its anticorrelations with other RSNs have been implicated in consciousness. However, the role of DAN-related functional patterns in drug-induced sedative effects is less clear. In the current study, we investigated altered functional connectivity of the DAN during midazolam-induced light sedation. In a placebo-controlled and within-subjects experimental study, fourteen healthy volunteers received midazolam or saline with a 1-week interval. Resting-state fMRI data were acquired before and after intravenous drug administration. A multiple region of interest-driven analysis was employed to investigate connectivity within and between RSNs. It was found that functional connectivity was significantly decreased by midazolam injection in two regions located in the left inferior parietal lobule and the left middle temporal area within the DAN as compared with the saline condition. We also identified three clusters in anticorrelation between the DAN and other RSNs for the interaction effect, which included the left medial prefrontal cortex, the right superior temporal gyrus, and the right superior frontal gyrus. Connectivity between all regions and DAN was significantly decreased by midazolam injection. The sensorimotor network was minimally affected. Midazolam decreased functional connectivity of the dorsal attention network. These findings advance the understanding of the neural mechanism of sedation, and such functional patterns might have clinical implications in other medical conditions related to patients with cognitive impairment.
Modernist Projects of Community-Based Urban Farms in Residential Areas—A Review of Agrarian Cooperatives in the Context of Contemporary Urban Development
Authors: Nowysz Aleksandra
Published: August 2021

This paper concerns the issue of food systems in the context of urban development. It describes relevant residential area ideas that integrate cities with food production, such as agrarian cooperatives. In the first section, modernist projects of residential areas linked with urban farms are reviewed, considering cooperative movement and the Industrial Revolution. This review shows that the aim of these historical projects was self-sufficiency and sustainability, based on local food production and broad areas covered by vegetation. They are considered to be a contemporary residential model. The second part of the paper discusses contemporary projects of farms within estates. The study demonstrates that the production of goods under urban agriculture goes beyond private goods, such as food produced for market or own use. The examples discussed show that urban farming performs key functions in residential architecture.
Spatiotemporal Changes in Vertical Heterogeneity: High-Rise Office Building Floor Space in Sydney, Australia
Authors: Han Hoon , Chen Haonan , Lee Jinwoo (Brian)
Published: August 2021

Mixed-use development is increasingly popular in land use planning and zoning, fostering a combination of residential, commercial, and cultural uses into one space. However, there is a lack of understanding of the vertical mix office space within a high-rise commercial building and the dynamics of the industry mix between buildings. This paper examines the spatiotemporal patterns of industry mix between and within office buildings in Sydney CBD from 2006 to 2017, using the data obtained from the City of Sydney floor space and employment surveys. This is the first study that identifies the dynamics of an industrial ecosystem in central Sydney, which has transformed to homophily land blocks, with increasing vertically heterogeneous office buildings, over the past decade. In addition, the study found that the significant clustering of anchor tenants, such as finances, hospitalities, and knowledge-based industries, are apparent.
Raman Spectroscopy and Machine Learning for IDH Genotyping of Unprocessed Glioma Biopsies
Authors: Sciortino Tommaso , Secoli Riccardo , d’Amico Ester , Moccia Sara , Conti Nibali Marco , Gay Lorenzo , Rossi Marco , Pecco Nicolò , Castellano Antonella , De Momi Elena , Fernandes Bethania , Riva Marco , Bello Lorenzo
Published: August 2021

Isocitrate dehydrogenase (IDH) mutational status is pivotal in the management of gliomas. Patients with IDH-mutated (IDH-MUT) tumors have a better prognosis and benefit more from extended surgical resection than IDH wild-type (IDH-WT). Raman spectroscopy (RS) is a minimally invasive optical technique with great potential for intraoperative diagnosis. We evaluated the RS’s ability to characterize the IDH mutational status onto unprocessed glioma biopsies. We extracted 2073 Raman spectra from thirty-eight unprocessed samples. The classification performance was assessed using the eXtreme Gradient Boosted trees (XGB) and Support Vector Machine with Radial Basis Function kernel (RBF-SVM). Measured Raman spectra displayed differences between IDH-MUT and IDH-WT tumor tissue. From the 103 Raman shifts screened as input features, the cross-validation loop identified 52 shifts with the highest performance in the distinction of the two groups. Raman analysis showed differences in spectral features of lipids, collagen, DNA and cholesterol/phospholipids. We were able to distinguish between IDH-MUT and IDH-WT tumors with an accuracy and precision of 87%. RS is a valuable and accurate tool for characterizing the mutational status of IDH mutation in unprocessed glioma samples. This study improves RS knowledge for future personalized surgical strategy or in situ target therapies for glioma tumors.
Neuroinflammation and Its Association with Cognition, Neuronal Markers and Peripheral Inflammation after Chemotherapy for Breast Cancer
Authors: Schroyen Gwen , Blommaert Jeroen , van Weehaeghe Donatienne , Sleurs Charlotte , Vandenbulcke Mathieu , Dedoncker Nina , Hatse Sigrid , Goris An , Koole Michel , Smeets Ann , van Laere Koen , Sunaert Stefan , Deprez Sabine
Published: August 2021

To uncover mechanisms underlying chemotherapy-induced cognitive impairment in breast cancer, we studied new biomarkers of neuroinflammation and neuronal survival. This cohort study included 74 women (47 ± 10 years) from 22 October 2017 until 20 August 2020. Nineteen chemotherapy-treated and 18 chemotherapy-naïve patients with breast cancer were assessed one month after the completion of surgery and/or chemotherapy, and 37 healthy controls were included. Assessments included neuropsychological testing, questionnaires, blood sampling for 17 inflammatory and two neuronal survival markers (neurofilament light-chain (NfL), and brain-derived neurotrophic factor (BDNF) and PET-MR neuroimaging. To investigate neuroinflammation, translocator protein (TSPO) [18F]DPA714-PET-MR was acquired for 15 participants per group, and evaluated by volume of distribution normalized to the cerebellum. Chemotherapy-treated patients showed higher TSPO expression, indicative for neuroinflammation, in the occipital and parietal lobe when compared to healthy controls or chemotherapy-naïve patients. After partial-volume correction, differences with healthy controls persisted (pFWE < 0.05). Additionally, compared to healthy- or chemotherapy-naïve controls, cognitive impairment (17–22%) and altered levels in blood markers (F ≥ 3.7, p ≤ 0.031) were found in chemotherapy-treated patients. NfL, an axonal damage marker, was particularly sensitive in differentiating groups (F = 105, p = 4.2 × 10 −21), with levels 20-fold higher in chemotherapy-treated patients. Lastly, in chemotherapy-treated patients alone, higher local TSPO expression was associated with worse cognitive performance, higher blood levels of BDNF/NfL, and decreased fiber cross-section in the corpus callosum (pFWE < 0.05). These findings suggest that increased neuroinflammation is associated with chemotherapy-related cognitive impairment in breast cancer. Additionally, NfL could be a useful biomarker to assess neurotoxic effects of anticancer chemotherapies.
MEM: An Algorithm for the Reliable Detection of Microsatellite Instability (MSI) on a Small NGS Panel in Colorectal Cancer
Authors: Herbreteau Guillaume , Airaud Fabrice , Pierre-Noël Elise , Vallée Audrey , Bézieau Stéphane , Théoleyre Sandrine , Blons Hélène , Garinet Simon , Denis Marc Guillaume
Published: August 2021

Purpose: MEM is an NGS algorithm that uses Expectation-Maximisation to detect the presence of unstable alleles from the NGS sequences of five microsatellites (BAT-25, BAT-26, NR-21, NR-24 and NR-27). The purpose of this study was to compare the MEM algorithm with a reference PCR method (MSI-PCR) and MisMatch Repair protein immunohistochemistry (MMR-IHC). Methods: FFPE colorectal cancer samples from 146 patients were analysed in parallel by MSI-PCR and NGS using the MEM algorithm. MMR-IHC results were available for 133 samples. Serial dilutions of an MSI positive control were performed to estimate the limit of detection. Results: the MEM algorithm was able to detect unstable alleles of each microsatellite with up to a 5% allelic fraction. Of the 146 samples, 28 (19.2%) were MSI in MSI-PCR. MEM algorithm results were in perfect agreement with those of MSI-PCR, at both MSI status and individual microsatellite level (Cohen’s kappa = 1). A high level of agreement was noted between MSI-PCR/MEM algorithm results and MMR-IHC results (Cohen’s kappa = 0.931). Conclusion: the MEM algorithm can determine the MSI status of colorectal cancer samples on a small NGS panel, using only five microsatellites approved by international guidelines, and can be combined with screening for targetable mutations.
A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis
Authors: Sereno María , Jimenez-Gordo Ana María , Baena-Espinar Javier , Aguado Carlos , Mielgo Xabier , Pertejo Ana , Álvarez-Álvarez Rosa , Sánchez Ana , López Jose Luis , Molina Raquel , López-Alfonso Ana , Hernández Berta , Chiara Luis Enrique , Martín Ana Manuela , López-Martín Ana , Dorta Miriam , Collazo-Lorduy Ana , Casado Enrique , de Molina Ana Ramirez , Colmenarejo Gonzalo
Published: August 2021

Background: Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2. Methods: Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death. Results: Among the 943 cancer patients screened, 83 patients (11.3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1.4, 95% CI [1,1,03,92], p-value = 0.01). Conclusions: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.
Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip
Authors: Dorrigiv Dina , Simeone Kayla , Communal Laudine , Kendall-Dupont Jennifer , St-Georges-Robillard Amélie , Péant Benjamin , Carmona Euridice , Mes-Masson Anne-Marie , Gervais Thomas
Published: August 2021

Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low. Several methodologies have been developed to address this issue, although no study has compared their efficacy in a controlled fashion. We investigated the effect of two variables in TECPs, specifically, the tissue size and culture vessel on tissue survival using micro-dissected tumor tissue (MDT) and tissue slices which were cultured in microfluidic chips and plastic well plates. Tumor models were produced from ovarian and prostate cancer cell line xenografts and were matched in terms of the specimen, total volume of tissue, and respective volume of medium in each culture system. We examined morphology, viability, and hypoxia in the various tumor models. Our observations suggest that the viability and proliferative capacity of MDTs were not affected during the time course of the experiments. In contrast, tissue slices had reduced proliferation and showed increased cell death and hypoxia under both culture conditions. Tissue slices cultured in microfluidic devices had a lower degree of hypoxia compared to those in 96-well plates. Globally, our results show that tissue slices have lower survival rates compared to MDTs due to inherent diffusion limitations, and that microfluidic devices may decrease hypoxia in tumor models.
Chemical Oral Cancerogenesis Is Impaired in PI3Kγ Knockout and Kinase-Dead Mice
Authors: Berta Giovanni Nicolao , Di Scipio Federica , Yang Zhiqian , Oberto Alessandra , Abbadessa Giuliana , Romano Federica , Carere Maria Elisabetta , Ceccarelli Adriano , Hirsch Emilio , Mognetti Barbara
Published: August 2021

We investigated the role of PI3Kγ in oral carcinogenesis by using a murine model of oral squamous carcinoma generated by exposure to 4-nitroquinoline 1-oxide (4NQO) and the continuous human cancer cell line HSC-2 and Cal-27. PI3Kγ knockout (not expressing PI3Kγ), PI3Kγ kinase-dead (carrying a mutation in the PI3Kγ gene causing loss of kinase activity) and wild-type (WT) C57Bl/6 mice were administered 4NQO via drinking water to induce oral carcinomas. At sacrifice, lesions were histologically examined and stained for prognostic tumoral markers (EGFR, Neu, cKit, Ki67) and inflammatory infiltrate (CD3, CD4, CD8, CD19 and CD68). Prevalence and incidence of preneoplastic and exophytic lesions were significantly and similarly delayed in both transgenic mice versus the control. The expression of prognostic markers, as well as CD19+ and CD68+ cells, was higher in WT, while T lymphocytes were more abundant in tongues isolated from transgenic mice. HSC-2 and Cal-27 cells were cultured in the presence of the specific PI3Kγ-inhibitor (IPI-549) which significantly impaired cell vitality in a dose-dependent manner, as shown by the MTT test. Here, we highlighted two different mechanisms, namely the modulation of the tumor-infiltrating cells and the direct inhibition of cancer-cell proliferation, which might impair oral cancerogenesis in the absence/inhibition of PI3Kγ.
The Extracellular Metabolome Stratifies Low and High Risk Potentially Premalignant Oral Keratinocytes and Identifies Citrate as a Potential Non-Invasive Marker of Tumour Progression
Authors: Karen-Ng Lee Peng , James Emma Louise , Stephen Abish , Bennett Mark Henry , Mycielska Maria Elzbieta , Parkinson Eric Kenneth
Published: August 2021

Premalignant oral lesions (PPOLs) which bypass senescence (IPPOL) have a much greater probability of progressing to malignancy, but pre-cancerous fields also contain mortal PPOL keratinocytes (MPPOL) that possess tumour-promoting properties. To identify metabolites that could potentially separate IPPOL, MPPOL and normal oral keratinocytes non-invasively in vivo, we conducted an unbiased screen of their conditioned medium. MPPOL keratinocytes showed elevated levels of branch-chain amino acid, lipid, prostaglandin, and glutathione metabolites, some of which could potentially be converted into volatile compounds by oral bacteria and detected in breath analysis. Extracellular metabolites were generally depleted in IPPOL, and only six were elevated, but some metabolites distinguishing IPPOL from MPPOL have been associated with progression to oral squamous cell carcinoma (OSCC) in vivo. One of the metabolites elevated in IPPOL relative to the other groups, citrate, was confirmed by targeted metabolomics and, interestingly, has been implicated in cancer growth and metastasis. Although our investigation is preliminary, some of the metabolites described here are detectable in the saliva of oral cancer patients, albeit at a more advanced stage, and could eventually help detect oral cancer development earlier.
Low Doses of Silver Nanoparticles Selectively Induce Lipid Peroxidation and Proteotoxic Stress in Mesenchymal Subtypes of Triple-Negative Breast Cancer
Authors: Snyder Christina M. , Rohde Monica M. , Fahrenholtz Cale D. , Swanner Jessica , Sloop John , Donati George L. , Furdui Cristina M. , Singh Ravi
Published: August 2021

Molecular profiling of tumors shows that triple-negative breast cancer (TNBC) can be stratified into mesenchymal (claudin-low breast cancer; CLBC) and epithelial subtypes (basal-like breast cancer; BLBC). Subtypes differ in underlying genetics and in response to therapeutics. Several reports indicate that therapeutic strategies that induce lipid peroxidation or proteotoxicity may be particularly effective for various cancers with a mesenchymal phenotype such as CLBC, for which no specific treatment regimens exist and outcomes are poor. We hypothesized that silver nanoparticles (AgNPs) can induce proteotoxic stress and cause lipid peroxidation to a greater extent in CLBC than in BLBC. We found that AgNPs were lethal to CLBCs at doses that had little effect on BLBCs and were non-toxic to normal breast epithelial cells. Analysis of mRNA profiles indicated that sensitivity to AgNPs correlated with expression of multiple CLBC-associated genes. There was no correlation between sensitivity to AgNPs and sensitivity to silver cations, uptake of AgNPs, or proliferation rate, indicating that there are other molecular factors driving sensitivity to AgNPs. Mechanistically, we found that the differences in sensitivity of CLBC and BLBC cells to AgNPs were driven by peroxidation of lipids, protein oxidation and aggregation, and subsequent proteotoxic stress and apoptotic signaling, which were induced in AgNP-treated CLBC cells, but not in BLBC cells. This study shows AgNPs are a specific treatment for CLBC and indicates that stratification of TNBC subtypes may lead to improved outcomes for other therapeutics with similar mechanisms of action.
Analytical Performance of NGS-Based Molecular Genetic Tests Used in the Diagnostic Workflow of Pheochromocytoma/Paraganglioma
Authors: Sarkadi Balazs , Liko Istvan , Nyiro Gabor , Igaz Peter , Butz Henriett , Patocs Attila
Published: August 2021

Next Generation Sequencing (NGS)-based methods are high-throughput and cost-effective molecular genetic diagnostic tools. Targeted gene panel and whole exome sequencing (WES) are applied in clinical practice for assessing mutations of pheochromocytoma/paraganglioma (PPGL) associated genes, but the best strategy is debated. Germline mutations of at the least 18 PPGL genes are present in approximately 20–40% of patients, thus molecular genetic testing is recommended in all cases. We aimed to evaluate the analytical and clinical performances of NGS methods for mutation detection of PPGL-associated genes. WES (three different library preparation and bioinformatics workflows) and an in-house, hybridization based gene panel (endocrine-onco-gene-panel- ENDOGENE) was evaluated on 37 (20 WES and 17 ENDOGENE) samples with known variants. After optimization of the bioinformatic workflow, 61 additional samples were tested prospectively. All clinically relevant variants were validated with Sanger sequencing. Target capture of PPGL genes differed markedly between WES platforms and genes tested. All known variants were correctly identified by all methods, but methods of library preparations, sequencing platforms and bioinformatical settings significantly affected the diagnostic accuracy. The ENDOGENE panel identified several pathogenic mutations and unusual genotype–phenotype associations suggesting that the whole panel should be used for identification of genetic susceptibility of PPGL.
Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer
Authors: Wen Sara W. C. , Andersen Rikke F. , Rasmussen Kristian , Thomsen Caroline Brenner , Hansen Torben Frøstrup , Nederby Line , Hager Henrik , Jakobsen Anders , Hilberg Ole
Published: August 2021

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated HOXA9 in bronchial lavage as a diagnostic biomarker of lung cancer. Participants were referred on suspicion of lung cancer. Ten mL lavage fluid was collected at bronchoscopy for analysis of methylated HOXA9 based on droplet digital PCR according to our previously published method. HOXA9 status was compared with the final diagnosis. The Discovery and Validation cohorts consisted of 101 and 95 consecutively enrolled participants, respectively. In the discovery cohort, the sensitivity and specificity were 73.1% (95% CI 60.9–83.2%) and 85.3% (95% CI 68.9–95.0%), respectively. In the validation cohort, the values were 80.0% (95% CI 66.3–90.0%) and 75.6% (95% CI 60.5–87.1%), respectively. A multiple logistic regression model including age, smoking status, and methylated HOXA9 status resulted in an AUC of 84.9% (95% CI 77.3–92.4%) and 85.9% (95% CI 78.4–93.4%) for the Discovery and Validation cohorts, respectively. Methylated HOXA9 in bronchial lavage holds potential as a supplementary tool in the diagnosis of lung cancer with a clinically relevant sensitivity and specificity. It remained significant when adjusting for age and smoking status.
Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis
Authors: Masson Walter , Lavalle-Cobo Augusto , Nogueira Juan Patricio
Published: August 2021

(1) Sodium–glucose cotransporter-2 inhibitors (SGLT2-i) reduce adipose tissue and cardiovascular events in patients with type 2 diabetes (T2D). Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and obstructive coronary disease events in patients with T2D. (2) We performed a systematic review and meta-analysis of SGLT2-i therapy on T2D patients, reporting data on changes in EAT after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A random effects or fixed effects model meta-analysis was then applied. (3) Results: A total of three studies (n = 64 patients with SGLT2-i, n = 62 with standard therapy) were included in the final analysis. SGLT2 inhibitors reduced EAT (SMD: −0.82 (−1.49; −0.15); p < 0.0001). An exploratory analysis showed that HbA1c was significantly reduced with SGLT2-i use, while body mass index was not significantly reduced with this drug. (4) Conclusions: This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with SGLT2-i treatment.
Cell Ferroptosis: New Mechanism and New Hope for Retinitis Pigmentosa
Authors: Yang Ming , So Kwok-Fai , Lam Wai-Ching , Lo Amy Cheuk Yin
Published: August 2021

Retinitis pigmentosa (RP) is a leading cause of inherited retinal degeneration, with more than 60 gene mutations. Despite the genetic heterogenicity, photoreceptor cell damage remains the hallmark of RP pathology. As a result, RP patients usually suffer from reduced night vision, loss of peripheral vision, decreased visual acuity, and impaired color perception. Although photoreceptor cell death is the primary outcome of RP, the underlying mechanisms are not completely elucidated. Ferroptosis is a novel programmed cell death, with characteristic iron overload and lipid peroxidation. Recent studies, using in vitro and in vivo RP models, discovered the involvement of ferroptosis-associated cell death, suggesting a possible new mechanism for RP pathogenesis. In this review, we discuss the association between ferroptosis and photoreceptor cell damage, and its implication in the pathogenesis of RP. We propose that ferroptotic cell death not only opens up a new research area in RP, but may also serve as a novel therapeutic target for RP.
Triggering Innate Immune Receptors as New Therapies in Alzheimer’s Disease and Multiple Sclerosis
Authors: Piec Pierre-Alexandre , Pons Vincent , Rivest Serge
Published: August 2021

Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate immunity in these pathologies. Most studies have been carried out in rodents and some of them have reported tremendous beneficial effects on the disease course. The modulation of innate immune cells is of great interest since it provides new hope for patients. In this review, we will briefly overview the therapeutic potential of some molecules and receptors in multiple sclerosis and Alzheimer’s disease and how they could be used to exploit new therapeutic avenues.
Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy
Authors: Tsui Yat-Ping , Lam Guy , Wu Kenneth Lap-Kei , Li Maximilian Tak-Sui , Tam Kin-Wai , Shum Daisy Kwok-Yan , Chan Ying-Shing
Published: August 2021

Transplantation of oligodendrocyte precursors (OPs) is potentially therapeutic for myelin disorders but a safe and accessible cell source remains to be identified. Here we report a two-step protocol for derivation of highly enriched populations of OPs from bone marrow stromal cells of young adult rats (aMSCs). Neural progenitors among the aMSCs were expanded in non-adherent sphere-forming cultures and subsequently directed along the OP lineage with the use of glial-inducing growth factors. Immunocytochemical and flow cytometric analyses of these cells confirmed OP-like expression of Olig2, PDGFRα, NG2, and Sox10. OPs so derived formed compact myelin both in vitro, as in co-culture with purified neurons, and in vivo, following transplantation into the corpus callosum of neonatal shiverer mice. Not only did the density of myelinated axons in the corpus callosum of recipient shiverer mice reach levels comparable to those in age-matched wild-type mice, but the mean lifespan of recipient shiverer mice also far exceeded those of non-recipient shiverer mice. Our results thus promise progress in harnessing the OP-generating potential of aMSCs towards cell therapy for myelin disorders.
Investigating Combustion Process of N-Butanol-Diesel Blends in a Diesel Engine with Variable Compression Ratio
Authors: Szabados György , Lukács Kristóf , Bereczky Ákos
Published: August 2021

The search for alternative fuels for internal combustion engines is ongoing. Among the alternatives, plant-based fuels can also be mentioned. Alcohol is not a common fuel for diesel engines because the physical and chemical properties of the alcohols are closer to those of gasoline. In our research, the combustion properties of diesel-n-butanol mixtures have been investigated to obtain results on the effect of butanol blending on combustion. Among the combustion properties, ignition delay, in-cylinder pressure, and heat release rate can be mentioned. They have been observed under different compression conditions on an engine on which the compression ratio can be adjusted. The method used was a quite simple one, so the speed of the engine was set to a constant 900 rpm without load, while three compression ratios (19.92, 15.27, and 12.53) were adjusted with a fuel flow rate of 13 mL/min and the pre-injection angle of 18° BTDC. Blending butanol into the investigated fuel does not significantly affect maximal values of indicated pressure, while much more effect on the pressure rising rate can be detected. Furthermore, heat release rate and ignition delay increased at every compression ratio investigated. Despite the low blending rates of butanol in the mixtures, butanol significantly affects the combustion parameters, especially at high compression ratios.
Multi-Objective Optimization of MIG Welding and Preheat Parameters for 6061-T6 Al Alloy T-Joints Using Artificial Neural Networks Based on FEM
Authors: Shao Qing , Tan Fuxing , Li Kai , Yoshino Tatsuo , Guo Guikai
Published: August 2021

To control the welding residual stress and deformation of metal inert gas (MIG) welding, the influence of welding process parameters and preheat parameters (welding speed, heat input, preheat temperature, and preheat area) is discussed, and a prediction model is established to select the optimal combination of process parameters. Thermomechanical numerical analysis was performed to obtain the residual welding deformation and stress according to a 100 × 150 × 50 × 4 mm aluminum alloy 6061-T6 T-joint. Owing to the complexity of the welding process, an optimal Latin hypercube sampling (OLHS) method was adopted for sampling with uniformity and stratification. Analysis of variance (ANOVA) was used to find the influence degree of welding speed (7.5–9 mm/s), heat input (1500–1700 W), preheat temperature (80–125 °C), and preheat area (12–36 mm). The range of research parameters are according to the material, welding method, thickness of the welding plate, and welding procedure specification. Artificial neural network (ANN) and multi-objective particle swarm optimization (MOPSO) was combined to find the effective parameters to minimize welding deformation and stress. The results showed that preheat temperature and welding speed had the greatest effect on the minimization of welding residual deformation and stress, followed by the preheat area, respectively. The Pareto front was obtained by using the MOPSO algorithm with ε-dominance. The welding residual deformation and stress are the minimum at the same time, when the welding parameters are selected as preheating temperature 85 °C and preheating area 12 mm, welding speed is 8.8 mm/s and heat input is 1535 W, respectively. The optimization results were validated by the finite element (FE) method. The error between the FE results and the Pareto optimal compromise solutions is less than 12.5%. The optimum solutions in the Pareto front can be chosen by designers according to actual demand.
Enhancement of Cleanliness and Deposition Rate by Understanding the Multiple Roles of the Showerhead Electrode in a Capacitively Coupled Plasma Reactor
Authors: Kim Ho Jun
Published: August 2021

Increasing the productivity of a showerhead-type capacitively coupled plasma (CCP) reactor requires an in-depth understanding of various physical phenomena related to the showerhead, which is not only responsible for gas distribution, but also acts as the electrode. Thus, we investigated how to enhance the cleanliness and deposition rate by studying the multiple roles of the showerhead electrode in a CCP reactor. We analyzed the gas transport in a three-dimensional complex geometry, and the SiH4/He discharges were simulated in a two-dimensional simplified geometry. The process volume was installed between the showerhead electrode (radio frequency powered) and the heater electrode (grounded). Our aim of research was to determine the extent to which the heated showerhead contributed to increasing the deposition rate and to reducing the size of the large particles generated during processing. The temperature of the showerhead was increased to experimentally measure the number of particles transported onto the heater to demonstrate the effects thereof on the decrease in contamination. The number of particles larger than 45 nm decreased by approximately 93% when the showerhead temperature increased from 373 to 553 K.
Low-Temperature Large-Area Zinc Oxide Coating Prepared by Atmospheric Microplasma-Assisted Ultrasonic Spray Pyrolysis
Authors: Shi Shih-Chen , Huang Po-Wei , Yang Jason Hsiao-Chun
Published: August 2021

Zinc oxide (ZnO) coatings have various unique properties and are often used in applications such as transparent conductive films in photovoltaic systems. This study developed an atmospheric-pressure microplasma-enhanced ultrasonic spray pyrolysis system, which can prepare large-area ZnO coatings at low temperatures under atmospheric-pressure conditions. The addition of an atmospheric-pressure microplasma-assisted process helped improve the preparation of ZnO coatings under atmospheric conditions, compared to using a conventional ultrasonic spray pyrolysis process, effectively reducing the preparation temperature to 350 °C. A program-controlled three-axis platform demonstrated its potential for the large-scale synthesis of ZnO coatings. The X-ray diffraction results showed that the ZnO coatings prepared by ultrasonic spray pyrolysis exhibited (002) preferred growth orientation and had a visible-light penetration rate of more than 80%. After vacuum treatment, the ZnO reached a 1.0 × 10−3 Ωcm resistivity and a transmittance of 82%. The tribology behavior of ZnO showed that the vacuum-annealed coating had a low degree of wear and a low coefficient of friction as the uniformly distributed and dense coating increased its load capacity.
The Relationship between Cyclic Multi-Scale Self-Organized Processes and Wear-Induced Surface Phenomena under Severe Tribological Conditions Associated with Buildup Edge Formation
Authors: Fox-Rabinovich German , Gershman Iosif S. , Locks Edinei , Paiva Jose M. , Endrino Jose L. , Dosbaeva Goulnara , Veldhuis Stephen
Published: August 2021

This paper presents experimental investigations of various interrelated multi-scale cyclic and temporal processes that occur on the frictional surface under severe tribological conditions during cutting with buildup edge formation. The results of the finite element modeling of the stress/temperature profiles on the friction surface are laid out. This study was performed on a multilayer coating with the top alumina ceramic layer deposited by CVD (chemical vapor deposition) on a WC/Co carbide substrate. A detailed analysis of the wear process was conducted by 3D wear evaluation, scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) and electron backscattered diffraction (EBSD), as well as X-ray photoelectron spectroscopy (XPS) methods. The following cyclic phenomena were observed on the surface of the tribo-system during the experiments: a repetitive formation and breakage of buildups (a self-organized critical process) and a periodical increase and decrease in the amount of thermal barrier tribo-films with a sapphire structure (which is a self-organization process). These two processes are interrelated with the accompanying progression of cratering, eventually resulting in the catastrophic failure of the entire tribo-system.
An Experimental Study of the Road Performance of Cement Stabilized Coal Gangue
Authors: Guan Junfeng , Lu Meng , Yao Xianhua , Wang Qing , Wang Decai , Yang Biao , Liu Huaizhong
Published: August 2021

The research into the road performance of coal gangue is of great significance for the consumption of coal gangue and reducing pollution. In this paper, the coal gangues were prepared by separation and crushing processes, and their gradations were also optimized. Aiming to identify the possible problems of coal gangue as a pavement base, an unconfined compressive strength test, a splitting test, a freeze–thaw test, and a drying shrinkage test of cement stabilized gangue with varying cement amounts were carried out, and the test results were compared and analyzed. The test results showed that the maximum dry density and optimum moisture content (OMC) of the optimized cement stabilized gangue and cement stabilized macadam increased with cement content. The maximum dry density and OMC of cement stabilized macadam were larger than that of cement stabilized gangue with the same cement content. The optimized 7-day unconfined compressive strength of cement stabilized gangue can meet the requirements for a secondary and lower highway base and subbase. The OMC and cement content are the critical factors affecting the compressive strength loss rate of cement stabilized gangue after freeze–thaw cycles. The smaller the OMC of cement stabilized gangue and the larger the cement content, the lower the compressive strength loss rate. With an increase in cement content, the drying shrinkage strain of cement stabilized gangue increased. The results show that a cement content of 4% is optimal for the cement stabilized coal gangue, which can be used for the light traffic base and heavy traffic subbase of class II and below highways. It provides a basis, guide, and reference for the application of coal gangue materials in a high-grade highway base.
Effect of Ultrafine Additives on the Morphology of Cement Hydration Products
Authors: Yakovlev Grigory , Drochytka Rostislav , Skripkiūnas Gintautas , Urkhanova Larisa , Polyanskikh Irina , Pudov Igor , Karpova Ekaterina , Saidova Zarina , Elrefai Ali E. M. M.
Published: August 2021

The present research is focused on the investigation of the influence of ultrafine additives on the structure formation of hardened cement paste and the establishment of the mechanisms of the morphological transformations, which determine the properties of hydrated products. In the course of the research, the modification of ordinary Portland cement was performed by the suspension of multi-walled carbon nanotubes (MWCNTs), carbon black (CB) paste, and silica fume (SF). Scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) microanalysis, X-ray diffraction (XRD) analysis, thermal analysis, and Fourier-transform infrared (FTIR) spectroscopy were used to study cement hydration products. The morphology of hardened cement paste depends on the chemical reactivity of additives, their geometry, and their genesis. The action mechanism of the inert carbon-based additives and pozzolanic silica fume were considered. The cement hydration products formed in the process of modification by both types of ultrafine additives are described. In the case of the modification of cement paste by inert MWCNTs and CB paste, the formation of cement hydration products on their surface without strong adhesion was observed, whereas in the case of the addition of SF separately and together with MWCNTs, the strong adhesion of additives and cement hydration products was noted.
Efficacy of Different Interventions to Reduce Pre- or Perioperative Blood Transfusion Rate in Patients with Colorectal Cancer: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Hung Chao-Ming , Chen Jiann-Jy , Zeng Bing-Yan , Zeng Bing-Syuan , Chen Yen-Wen , Suen Mein-Woei , Wu Ming-Kung , Tseng Ping-Tao
Published: August 2021

Background: The high proportion of blood transfusions before and during surgery carries unnecessary risk and results in poor prognosis in colorectal cancer patients. Different pharmacological interventions (i.e., iron supplement or recombinant erythropoietin) to reduce blood transfusion rates have shown inconclusive results. Methods: This network meta-analysis (NMA) consisted of randomized controlled trials (RCTs) comparing the efficacy of different pharmacologic interventions (i.e., iron supplementation or recombinant erythropoietin) to reduce the blood transfusion rate. NMA statistics were conducted using the frequentist model. Results: Seven RCTs (688 participants) were included in this study. The NMA demonstrated that the combination of high-dose recombinant human erythropoietin and oral iron supplements was associated with the least probability of receiving a blood transfusion [odds ratio = 0.24, 95% confidence intervals (95% CIs): 0.08 to 0.73] and best reduced the amount of blood transfused if blood transfusion was necessary (mean difference = −2.62 U, 95% CI: −3.55 to −1.70 U) when compared to the placebo/control group. None of the investigated interventions were associated with any significantly different dropout rate compared to the placebo/control group. Conclusions: The combination of high-dose recombinant human erythropoietin and oral iron supplements might be considered as a choice for reducing the rate of blood transfusion in patients with colorectal cancer. However, future large-scale RCT with long-term follow-up should be warranted to approve the long-term safety.