bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Effects of Childhood Cancer Treatment on Dentition and Oral Health: A Dentist Survey Study from the DCCSS LATER 2 Study
Authors: Stolze Juliette , Vlaanderen Kim C. E. , Holtbach Frederique C. E. D. , Teepen Jop C. , Kremer Leontien C. M. , Loonen Jacqueline J. , van Dulmen-den Broeder Eline , Heuvel-Eibrink Marry M. van den , Pal Helena J. H. van der , Versluys Birgitta , van der Heiden-van der Loo Margriet , Louwerens Marloes , Raber-Durlacher Judith E. , Bresters Dorine , Brand Henk S.
Published: October 2021

Objectives: The aim of this study was to identify the prevalence of and independent risk factors for long-term effects of childhood cancer treatment on the dentition and oral health in childhood cancer survivors (CCSs). Methods: This cross-sectional study is part of the Dutch Childhood Cancer Survivor Study (DCCSS) LATER 2. CCSs were diagnosed with cancer between 1963 and 2001. This study focuses on survey data of 154 CCSs on whom information about their oral health was received from their dentists (71.3%). Descriptive statistics and univariable and multivariable Poisson regression analyses were performed to determine the association between treatment characteristics and oral health data. Results: Of the study group, 36.3% had at least one DDD. The most prevalent DDDs were short-root anomaly (14.6%), agenesis (14.3%), and microdontia (13.6%). Risk factors for at least one DDD were younger age at diagnosis (<3 years) and dose-dependent alkylating agent therapy. Conclusions: This study provides more insight into risk factors for oral health problems in Dutch CCSs. This information is essential in order to improve early detection, prevention, dental care, and quality of life. Further studies are needed in order to better define dose-related radiotherapy exposure of the developing teeth in correlation with oral health problems.
Interaction of Opioids with TLR4—Mechanisms and Ramifications
Authors: Gabr Mai Mahmoud , Saeed Iqira , Miles Jared A. , Ross Benjamin P. , Shaw Paul Nicholas , Hollmann Markus W. , Parat Marie-Odile
Published: October 2021

The innate immune receptor toll-like receptor 4 (TLR4) is known as a sensor for the gram-negative bacterial cell wall component lipopolysaccharide (LPS). TLR4 activation leads to a strong pro-inflammatory response in macrophages; however, it is also recognised to play a key role in cancer. Recent studies of the opioid receptor (OR)-independent actions of opioids have identified that TLR4 can respond to opioids. Opioids are reported to weakly activate TLR4, but to significantly inhibit LPS-induced TLR4 activation. The action of opioids at TLR4 is suggested to be non-stereoselective, this is because OR-inactive (+)-isomers of opioids have been shown to activate or to inhibit TLR4 signalling, although there is some controversy in the literature. While some opioids can bind to the lipopolysaccharide (LPS)-binding cleft of the Myeloid Differentiation factor 2 (MD-2) co-receptor, pharmacological characterisation of the inhibition of opioids on LPS activation of TLR4 indicates a noncompetitive mechanism. In addition to a direct interaction at the receptor, opioids affect NF-κB activation downstream of both TLR4 and opioid receptors and modulate TLR4 expression, leading to a range of in vivo outcomes. Here, we review the literature reporting the activity of opioids at TLR4, its proposed mechanism(s), and the complex functional consequences of this interaction.
Hepatic Arterial Infusion Chemotherapy with Cisplatin versus Sorafenib for Intrahepatic Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Analysis
Authors: Zaizen Yuki , Nakano Masahito , Fukumori Kazuta , Yano Yoichi , Takaki Kota , Niizeki Takashi , Kuwaki Kotaro , Fukahori Masaru , Sakaue Takahiko , Yoshimura Sohei , Nakazaki Mika , Kuromatsu Ryoko , Okamura Shusuke , Iwamoto Hideki , Shimose Shigeo , Shirono Tomotake , Noda Yu , Kamachi Naoki , Koga Hironori , Torimura Takuji
Published: October 2021

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled 331 patients with intrahepatic advanced HCC who received HAIC with cisplatin (n = 88) or sorafenib (n = 243) between June 2006 and March 2020. No significant difference was observed in OS between HAIC with cisplatin and sorafenib cohorts (median survival time [MST]: 14.0 vs. 12.3 months; p = 0.0721). To reduce confounding effects, 166 patients were selected using propensity score-matched analysis (n = 83 for each treatment). HAIC with cisplatin significantly prolonged OS compared with sorafenib (MST: 15.6 vs. 11.0 months; p = 0.0157). Following stratification according to the Child-Pugh classification, for patients with class A (MST: 24.0 vs. 15.0 months; p = 0.0145), HAIC with cisplatin rather than sorafenib significantly prolonged OS. Our findings suggest that HAIC with cisplatin demonstrates longer prognostic effects than sorafenib in intrahepatic advanced HCC.
Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
Authors: Khan Sabbir , Mahalingam Rajasekaran , Sen Shayak , Martinez-Ledesma Emmanuel , Khan Arshad , Gandy Kaitlin , Lang Frederick F. , Sulman Erik P. , Alfaro-Munoz Kristin D. , Majd Nazanin K. , Balasubramaniyan Veerakumar , de Groot John F.
Published: October 2021

Interferon (IFN) signaling contributes to stemness, cell proliferation, cell death, and cytokine signaling in cancer and immune cells; however, the role of IFN signaling in glioblastoma (GBM) and GBM stem-like cells (GSCs) is unclear. Here, we investigated the role of cancer-cell-intrinsic IFN signaling in tumorigenesis in GBM. We report here that GSCs and GBM tumors exhibited differential cell-intrinsic type I and type II IFN signaling, and high IFN/STAT1 signaling was associated with mesenchymal phenotype and poor survival outcomes. In addition, chronic inhibition of IFN/STAT1 signaling decreased cell proliferation and mesenchymal signatures in GSCs with intrinsically high IFN/STAT1 signaling. IFN-β exposure induced apoptosis in GSCs with intrinsically high IFN/STAT1 signaling, and this effect was abolished by the pharmacological inhibitor ruxolitinib and STAT1 knockdown. We provide evidence for targeting IFN signaling in a specific sub-group of GBM patients. IFN-β may be a promising candidate for adjuvant GBM therapy.
Network-Based Analysis to Identify Drivers of Metastatic Prostate Cancer Using GoNetic
Authors: de Schaetzen van Brienen Louise , Miclotte Giles , Larmuseau Maarten , Van den Eynden Jimmy , Marchal Kathleen
Published: October 2021

Most known driver genes of metastatic prostate cancer are frequently mutated. To dig into the long tail of rarely mutated drivers, we performed network-based driver identification on the Hartwig Medical Foundation metastatic prostate cancer data set (HMF cohort). Hereto, we developed GoNetic, a method based on probabilistic pathfinding, to identify recurrently mutated subnetworks. In contrast to most state-of-the-art network-based methods, GoNetic can leverage sample-specific mutational information and the weights of the underlying prior network. When applied to the HMF cohort, GoNetic successfully recovered known primary and metastatic drivers of prostate cancer that are frequently mutated in the HMF cohort (TP53, RB1, and CTNNB1). In addition, the identified subnetworks contain frequently mutated genes, reflect processes related to metastatic prostate cancer, and contain rarely mutated driver candidates. To further validate these rarely mutated genes, we assessed whether the identified genes were more mutated in metastatic than in primary samples using an independent cohort. Then we evaluated their association with tumor evolution and with the lymph node status of the patients. This resulted in forwarding several novel putative driver genes for metastatic prostate cancer, some of which might be prognostic for disease evolution.
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C
Authors: Funke Lukas , Bracht Thilo , Oeck Sebastian , Schork Karin , Stepath Markus , Dreesmann Sabine , Eisenacher Martin , Sitek Barbara , Schramm Alexander
Published: October 2021

(1) Background: Neuroblastomas (NBs) are the most common extracranial solid tumors of children. The amplification of the Myc-N proto-oncogene (MYCN) is a major driver of NB aggressiveness, while high expression of the neurotrophin receptor NTRK1/TrkA is associated with mild disease courses. The molecular effects of NTRK1 signaling in MYCN-amplified NB, however, are still poorly understood and require elucidation. (2) Methods: Inducible NTRK1 expression was realized in four NB cell lines with (IMR5, NGP) or without MYCN amplification (SKNAS, SH-SY5Y). Proteome and phosphoproteome dynamics upon NTRK1 activation by its ligand, NGF, were analyzed in a time-dependent manner in IMR5 cells. Target validation by immunofluorescence staining and automated image processing was performed using the three other NB cell lines. (3) Results: In total, 230 proteins and 134 single phosphorylated class I phosphosites were found to be significantly regulated upon NTRK1 activation. Among known NTRK1 targets, Stathmin and the neurosecretory protein VGF were recovered. Additionally, we observed the upregulation and phosphorylation of Lamin A/C (LMNA) that accumulated inside nuclear foci. (4) Conclusions: We provide a comprehensive picture of NTRK1-induced proteome and phosphoproteome dynamics. The phosphorylation of LMNA within nucleic aggregates was identified as a prominent feature of NTRK1 signaling independent of the MYCN status of NB cells.
Characterization of a New L-Glutaminase Produced by Achromobacter xylosoxidans RSHG1, Isolated from an Expired Hydrolyzed L-Glutamine Sample
Authors: Saleem Rabia , Ahmed Safia
Published: October 2021

As significant biocatalyst, L-glutaminases find potential applications in various fields, from nourishment to the pharmaceutical industry. Anticancer activity and flavor enhancement are the most promising applications of L-glutaminases. In this study, L-glutaminase was isolated and purified from an old glutamine sample. A selected bacterial isolate was characterized taxonomically by morphological characters, biochemical testing and 16S rDNA sequence homology testing. The taxonomical characterization of the isolate identified it as Achromobacter xylosoxidans strain RSHG1. The isolate showed maximum enzyme production at 30 °C, pH 9, with Sorbitol as a carbon source and L-Glutamine as a nitrogen and inducer source. L-Glutaminsae was purified by using column chromatography on a Sephadex G-75. The enzyme has a molecular weight of 40 KDa, pH optimal 7 and is stable in the pH range of 6–8. The optimum temperature for the catalyst was 40 °C and stable at 35–50 °C. The kinetic studies of the purified L-glutaminase exhibited Km and Vmax of 0.236 mM and 443.8 U/mg, respectively. L-Glutaminase activity was increased when incubated with 20 mM CaCl2, BaCl2, ZnSO4, KCl, MgSO4 and NaCl, whereas EDTA, CoCl2, HgCl, ZnSO4 and FeSO4 decreased the activity of the enzyme. The addition of 8% NaCl enhanced the glutaminase activity. L-Glutaminase immobilized on 3.6% agar was stable for up to 3 weeks.
BaF(p-BDC)0.5 as the Catalyst Precursor for the Catalytic Dehydrochlorination of 1-Chloro-1,1-Difluoroethane to Vinylidene Fluoride
Authors: Wang Shucheng , Wang Chuanzhao , Yu Houlin , Yu Wei , Liu Yongnan , Liu Wucan , Zhou Feixiang , Yu Wanjin , Wang Jiuju , Zhang Jianjun , Han Wenfeng
Published: October 2021

A BaF(p-BDC)0.5 catalyst was prepared by solid state reaction at room temperature with Ba(OH)2 as precursor, NH4F as F source, and H2(p-BDC) as organic ligand. The calcined samples were used as catalysts for dehydrochlorination of 1-chloro-1,1-difluoroethane to generate vinylidene fluoride (VDF) at 350 °C. Commercial production of VDF is carried out at 600–700 °C. Clearly, pyrolysis of the BaF(p-BDC)0.5 catalyst provided a promising way to prepare VDF at low temperatures. Prior to calcination, the activity of the BaF(p-BDC)0.5 catalyst was low. Following calcination at high temperatures, BaF(p-BDC)0.5 decomposed to BaF2 and BaCO3, and then the catalyst was chlorinated and fluorinated to BaClF, which showed high activity and stable VDF selectivity for dehydrochlorination of 1-Chloro-1,1-Difluoroethane to VDF.
Naphthyl-Naphthalimides as High-Performance Visible Light Photoinitiators for 3D Printing and Photocomposites Synthesis
Authors: Rahal Mahmoud , Graff Bernadette , Toufaily Joumana , Hamieh Tayssir , Ibrahim-Ouali Malika , Dumur Frédéric , Lalevée Jacques
Published: October 2021

In this article, five new organic dyes based on the naphthalimide scaffold (Napht-1–Napht-5) were synthesized and tested as high-performance photoinitiators for both the Free Radical Photopolymerization (FRP) of acrylates and the Cationic Polymerization (CP) of epoxides using blue Light-Emitting Diodes (LEDs) as a safe irradiation source (LED @405 nm and 455). In fact, very good photopolymerization profiles (high final conversions and high polymerization rates) were obtained once these photoinitiators were combined with an Iodonium salt (Iod) or Iod/amine NPG and NVK). Remarkably, these dyes were able to generate interpenetrating polymer networks (IPN) by polymerization of a blend of monomers. These experiments were carried out to improve the polymerization profiles as well as the mechanical properties of the obtained materials. Due to their high photoinitiation abilities, these compounds were used in some applications such as photocomposite synthesis, direct laser write, and 3D printing experiments. To determine the chemical mechanisms, the photochemical/photophysical properties of these compounds were studied using different characterization techniques such as UV–visible absorption spectroscopy, steady-state photolysis, Fluorescence quenching, time-resolved fluorescence spectroscopy, FTIR spectroscopy, and cyclic voltammetry
Gfi1 Loss Protects against Two Models of Induced Diabetes
Authors: Napolitano Tiziana , Avolio Fabio , Silvano Serena , Forcisi Sara , Pfeifer Anja , Vieira Andhira , Navarro-Sanz Sergi , Friano Marika Elsa , Ayachi Chaïma , Garrido-Utrilla Anna , Atlija Josipa , Hadzic Biljana , Becam Jérôme , Sousa-De-Veiga Anette , Plaisant Magali Dodille , Balaji Shruti , Pisani Didier F. , Mondin Magali , Schmitt-Kopplin Philippe , Amri Ez-Zoubir , Collombat Patrick
Published: October 2021

Background: Although several approaches have revealed much about individual factors that regulate pancreatic development, we have yet to fully understand their complicated interplay during pancreas morphogenesis. Gfi1 is transcription factor specifically expressed in pancreatic acinar cells, whose role in pancreas cells fate identity and specification is still elusive. Methods: In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for Gfi1 specifically in the pancreas. Gfi1 conditional knockout animals were phenotypically characterized by immunohistochemistry, RT-qPCR, and RNA scope. To assess the role of Gfi1 in the pathogenesis of diabetes, we challenged Gfi1-deficient mice with two models of induced hyperglycemia: long-term high-fat/high-sugar feeding and streptozotocin injections. Results: Interestingly, mutant mice did not show any obvious deleterious phenotype. However, in depth analyses demonstrated a significant decrease in pancreatic amylase expression, leading to a diminution in intestinal carbohydrates processing and thus glucose absorption. In fact, Gfi1-deficient mice were found resistant to diet-induced hyperglycemia, appearing normoglycemic even after long-term high-fat/high-sugar diet. Another feature observed in mutant acinar cells was the misexpression of ghrelin, a hormone previously suggested to exhibit anti-apoptotic effects on β-cells in vitro. Impressively, Gfi1 mutant mice were found to be resistant to the cytotoxic and diabetogenic effects of high-dose streptozotocin administrations, displaying a negligible loss of β-cells and an imperturbable normoglycemia. Conclusions: Together, these results demonstrate that Gfi1 could turn to be extremely valuable for the development of new therapies and could thus open new research avenues in the context of diabetes research.
The Organization of Pericentromeric Heterochromatin in Polytene Chromosome 3 of the Drosophila melanogaster Line with the Rif11; SuURES Su(var)3-906 Mutations Suppressing Underreplication
Authors: Zykova Tatyana , Maltseva Mariya , Goncharov Fedor , Boldyreva Lidia , Pokholkova Galina , Kolesnikova Tatyana , Zhimulev Igor
Published: October 2021

Although heterochromatin makes up 40% of the Drosophila melanogaster genome, its organization remains little explored, especially in polytene chromosomes, as it is virtually not represented in them due to underreplication. Two all-new approaches were used in this work: (i) with the use of a newly synthesized Drosophila line that carries three mutations, Rif11, SuURES and Su(var)3-906, suppressing the underreplication of heterochromatic regions, we obtained their fullest representation in polytene chromosomes and described their structure; (ii) 20 DNA fragments with known positions on the physical map as well as molecular genetic features of the genome (gene density, histone marks, heterochromatin proteins, origin recognition complex proteins, replication timing sites and satellite DNAs) were mapped in the newly polytenized heterochromatin using FISH and bioinformatics data. The borders of the heterochromatic regions and variations in their positions on arm 3L have been determined for the first time. The newly polytenized heterochromatic material exhibits two main types of morphology: a banding pattern (locations of genes and short satellites) and reticular chromatin (locations of large blocks of satellite DNA). The locations of the banding and reticular polytene heterochromatin was determined on the physical map.
Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
Authors: Gong Xiaoting , Yan Huige , Ma Junfan , Zhu Zhu , Zhang Shenghua , Xu Weiyan , Huang Jing , Qiu Xiaoyan
Published: October 2021

Immunoglobulin (Ig), a characteristic marker of B cells, is a multifunctional evolutionary conserved antibody critical for maintaining tissue homeostasis and developing fully protective humoral responses to pathogens. Increasing evidence revealed that Ig is widely expressed in non-immune cells; moreover, Ig produced by different lineages cells plays different biological roles. Recently, it has been reported that monocytes or macrophages also express Ig. However, its function remains unclear. In this study, we further identified that Ig, especially Ig mu heavy chain (IgM), was mainly expressed in mice macrophages. We also analyzed the IgM repertoire characteristic in macrophages and found that the VHDJH rearrangements of macrophage-derived IgM showed a restricted and conservative VHDJH pattern, which differed from the diverse VHDJH rearrangement pattern of the B cell-expressed IgM in an individual. Functional investigation showed that IgM knockdown significantly promoted macrophage migration and FAK/Src-Akt axis activation. Furthermore, some inflammatory cytokines such as MCP1 and IL-6 increased after IgM knockdown under LPS stimulation. A mechanism study revealed that the IgM interacted with binding immunoglobulin protein (Bip) and inhibited inflammatory response and unfolded protein response (UPR) activation in macrophages. Our data elucidate a previously unknown function of IgM in macrophages that explains its ability to act as a novel regulator of Bip to participate in endoplasmic reticulum stress and further regulate the inflammatory response.
Impact of Lipoprotein(a) Levels on Perioperative Outcomes in Cardiac Surgery
Authors: Heinisch Paul Philipp , Mihalj Maks , Huber Markus , Schefold Joerg C. , Hartmann Alexander , Walter Michael , Steinhagen-Thiessen Elisabeth , Schmidli Juerg , Stüber Frank , Räber Lorenz , Luedi Markus M
Published: October 2021

Altered lipid metabolism has been shown to be of major importance in a range of metabolic diseases, with particular importance in cardiovascular disease (CVD). As a key metabolic product, altered lipoprotein(a) (Lp(a)) levels may be associated with adverse clinical outcomes in high-risk cardiovascular patients undergoing cardiac surgery. We aimed to investigate the impact of the important metabolite Lp(a) on complications and clinical outcomes in high-risk patients. A prospective observational cohort study was performed. Data were derived from the Bern Perioperative Biobank (ClinicalTrials.gov NCT04767685), and included 192 adult patients undergoing elective cardiac surgery. Blood samples were collected at 24 h preoperatively, before induction of general anaesthesia, upon weaning from cardiopulmonary bypass (CPB), and the first morning after surgery. Clinical endpoints included stroke, myocardial infarction, and mortality within 30 days after surgery or within 1 year. Patients were grouped according to their preoperative Lp(a) levels: <30 mg/dL (n = 121; 63%) or >30 mg/dL (n = 71, 37%). The groups with increased vs. normal Lp(a) levels were comparable with regard to preoperative demographics and comorbidities. Median age was 67 years (interquartile range (IQR) 60.0, 73.0), with median body mass index (BMI) of 23.1 kg/m2 (23.7, 30.4), and the majority of patients being males (75.5%). Over the observational interval, Lp(a) levels decreased in all types of cardiac surgery after CPB (mean decline of approximately −5 mg/dL). While Lp(a) levels decreased in all patients following CPB, this observation was considerably pronounced in patients undergoing deep hypothermic circulatory arrest (DHCA) (decrease to preoperative Lp(a) levels by −35% (95% CI −68, −1.7), p = 0.039). Increased Lp(a) levels were neither associated with increased rates of perioperative stroke or major adverse events in patients undergoing cardiac surgery, nor with overall mortality in the perioperative period, or at one year after surgery. Other than for cohorts in neurology and cardiology, elevated Lp(a) might not be a risk factor for perioperative events in cardiac surgery.
Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies
Authors: Jin Qiao , Ma Ronald Ching Wan
Published: October 2021

The increasing prevalence of diabetes and its complications, such as cardiovascular and kidney disease, remains a huge burden globally. Identification of biomarkers for the screening, diagnosis, and prognosis of diabetes and its complications and better understanding of the molecular pathways involved in the development and progression of diabetes can facilitate individualized prevention and treatment. With the advancement of analytical techniques, metabolomics can identify and quantify multiple biomarkers simultaneously in a high-throughput manner. Providing information on underlying metabolic pathways, metabolomics can further identify mechanisms of diabetes and its progression. The application of metabolomics in epidemiological studies have identified novel biomarkers for type 2 diabetes (T2D) and its complications, such as branched-chain amino acids, metabolites of phenylalanine, metabolites involved in energy metabolism, and lipid metabolism. Metabolomics have also been applied to explore the potential pathways modulated by medications. Investigating diabetes using a systems biology approach by integrating metabolomics with other omics data, such as genetics, transcriptomics, proteomics, and clinical data can present a comprehensive metabolic network and facilitate causal inference. In this regard, metabolomics can deepen the molecular understanding, help identify potential therapeutic targets, and improve the prevention and management of T2D and its complications. The current review focused on metabolomic biomarkers for kidney and cardiovascular disease in T2D identified from epidemiological studies, and will also provide a brief overview on metabolomic investigations for T2D.
IPF-Fibroblast Erk1/2 Activity Is Independent from microRNA Cluster 17-92 but Can Be Inhibited by Treprostinil through DUSP1
Authors: Blumer Sabrina , Fang Lei , Chen Wei-Chih , Khan Petra , Hostettler Katrin , Tamm Michael , Roth Michael , Lambers Christopher
Published: October 2021

Idiopathic pulmonary fibrosis (IPF) is a progressive terminal lung disease, and therapies aim to block fibrosis. Fibroblast proliferation is controlled by C/EBP-β, microRNA cluster 17-92 (miR17-92), and Erk1/2 mitogen-activated protein kinase. This study assessed the role of miR17-92 in IPF-fibroblast proliferation and its modification by treprostinil. Fibroblasts were isolated from eight IPF patients, five interstitial lung fibrosis patients, and seven control lungs. Fibroblasts were stimulated with TGF-β1 over 24 h. The miR17-92 expression was analyzed by RT-qPCR, and protein expression by Western blotting. TGF-β1 upregulated C/EBP-β in all fibroblasts, which was reduced by treprostinil in control-fibroblasts, but not in IPF-fibroblasts. Compared to controls, the guide strands miR-19a-3p, miR-19b-3p, miR-20a-5p, and miR-92a-3p, as well as the passenger strands miR-17-3p, miR-18-3p, miR-19a-1-5p, and miR-92a-5p were significantly increased in IPF-fibroblasts. In controls, TGF-β1 and treprostinil significantly reduced specific miR17-92 members. IPF-fibroblast proliferation was inhibited by treprostinil through increased expression of the Erk1/2 inhibitor DUSP1. These data suggest that proliferation control via miR17-92 and C/EBP-β is disrupted in IPF-fibroblasts. Therefore, the inhibition of early stages of signaling cascades or specific mitogen receptors might be less effective. However, the increased proliferation is sensitive to Erk1/2 inhibition by treprostinil-induced DUSP1.
Effects of Sample Size on Plant Single-Cell RNA Profiling
Authors: Chen Hongyu , Lv Yang , Yin Xinxin , Chen Xi , Chu Qinjie , Zhu Qian-Hao , Fan Longjiang , Guo Longbiao
Published: October 2021

Single-cell RNA (scRNA) profiling or scRNA-sequencing (scRNA-seq) makes it possible to parallelly investigate diverse molecular features of multiple types of cells in a given plant tissue and discover cell developmental processes. In this study, we evaluated the effects of sample size (i.e., cell number) on the outcome of single-cell transcriptome analysis by sampling different numbers of cells from a pool of ~57,000 Arabidopsis thaliana root cells integrated from five published studies. Our results indicated that the most significant principal components could be achieved when 20,000–30,000 cells were sampled, a relatively high reliability of cell clustering could be achieved by using ~20,000 cells with little further improvement by using more cells, 96% of the differentially expressed genes could be successfully identified with no more than 20,000 cells, and a relatively stable pseudotime could be estimated in the subsample with 5000 cells. Finally, our results provide a general guide for optimizing sample size to be used in plant scRNA-seq studies.
Thermodynamic Study of Adsorption Capacity between Metal Film and Optical Crystal: Adsorption Energy of Ni Films on LiNbO3 Substrates
Authors: Xu Yuhang , Lu Fei , Liu Kaijing , Ma Changdong
Published: October 2021

The growth of large areas of two-dimensional homogeneous graphene depends on the bond between the metal film, which acts as a catalyst, and the substrate material. The structural differences between the metal and the various anisotropic crystals make this growth method a challenge for the feasibility of growing graphene on optical crystals. In this paper, the evolution of the adsorption energy between nickel (Ni) films and Lithium Niobate (LiNbO3, LN) crystals is modelled under different thermal treatment environments by constructing a physical model of the temperature dependence of the adsorption energy between the two materials. With the aid of a series of simulated full annealing processes, the changes in adsorption energy at different temperatures were calculated. The results show that there are two “temperature windows” with target annealing temperatures of 700–800 K and 950–1050 K that prove to have high adsorption energies. This is of great guiding and practical significance for the direct transfer-free synthesis of graphene on LiNbO3 substrates.
Human Cytomegalovirus Is Associated with Lower HCC Recurrence in Liver Transplant Patients
Authors: Hsu Po-Jung , Hung Hao-Chien , Lee Jin-Chiao , Wang Yu-Chao , Cheng Chih-Hsien , Wu Tsung-Han , Wu Ting-Jung , Chou Hong-Shiue , Chan Kun-Ming , Lee Wei-Chen , Lee Chen-Fang
Published: October 2021

Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia (p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20–0.97), microscopic vascular invasion (p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78–8.36), and tumor status beyond the Milan criteria (p = 0.001; OR = 3.69; 95% CI = 1.77–7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.
Lot Streaming in Different Types of Production Processes: A PRISMA Systematic Review
Authors: Salazar-Moya Alexandra , Garcia Marcelo V.
Published: October 2021

At present, any industry that wanted to be considered a vanguard must be willing to improve itself, developing innovative techniques to generate a competitive advantage against its direct competitors. Hence, many methods are employed to optimize production processes, such as Lot Streaming, which consists of partitioning the productive lots into overlapping small batches to reduce the overall operating times known as Makespan, reducing the delivery time to the final customer. This work proposes carrying out a systematic review following the PRISMA methodology to the existing literature in indexed databases that demonstrates the application of Lot Streaming in the different production systems, giving the scientific community a strong consultation tool, useful to validate the different important elements in the definition of the Makespan reduction objectives and their applicability in the industry. Two hundred papers were identified on the subject of this study. After applying a group of eligibility criteria, 63 articles were analyzed, concluding that Lot Streaming can be applied in different types of industrial processes, always keeping the main objective of reducing Makespan, becoming an excellent improvement tool, thanks to the use of different optimization algorithms, attached to the reality of each industry.
Investigation of MALDI-TOF Mass Spectrometry for Assessing the Molecular Diversity of Campylobacter jejuni and Comparison with MLST and cgMLST: A Luxembourg One-Health Study
Authors: Feucherolles Maureen , Nennig Morgane , Becker Sören L. , Martiny Delphine , Losch Serge , Penny Christian , Cauchie Henry-Michel , Ragimbeau Catherine
Published: October 2021

There is a need for active molecular surveillance of human and veterinary Campylobacter infections. However, sequencing of all isolates is associated with high costs and a considerable workload. Thus, there is a need for a straightforward complementary tool to prioritize isolates to sequence. In this study, we proposed to investigate the ability of MALDI-TOF MS to pre-screen C. jejuni genetic diversity in comparison to MLST and cgMLST. A panel of 126 isolates, with 10 clonal complexes (CC), 21 sequence types (ST) and 42 different complex types (CT) determined by the SeqSphere+ cgMLST, were analysed by a MALDI Biotyper, resulting into one average spectra per isolate. Concordance and discriminating ability were evaluated based on protein profiles and different cut-offs. A random forest algorithm was trained to predict STs. With a 94% similarity cut-off, an AWC of 1.000, 0.933 and 0.851 was obtained for MLSTCC, MLSTST and cgMLST profile, respectively. The random forest classifier showed a sensitivity and specificity up to 97.5% to predict four different STs. Protein profiles allowed to predict C. jejuni CCs, STs and CTs at 100%, 93% and 85%, respectively. Machine learning and MALDI-TOF MS could be a fast and inexpensive complementary tool to give an early signal of recurrent C. jejuni on a routine basis.
A Trust-Based Methodology to Evaluate Deep Learning Models for Automatic Diagnosis of Ocular Toxoplasmosis from Fundus Images
Authors: Parra Rodrigo , Ojeda Verena , Vázquez Noguera Jose Luis , García-Torres Miguel , Mello-Román Julio César , Villalba Cynthia , Facon Jacques , Divina Federico , Cardozo Olivia , Castillo Verónica Elisa , Matto Ingrid Castro
Published: October 2021

In the automatic diagnosis of ocular toxoplasmosis (OT), Deep Learning (DL) has arisen as a powerful and promising approach for diagnosis. However, despite the good performance of the models, decision rules should be interpretable to elicit trust from the medical community. Therefore, the development of an evaluation methodology to assess DL models based on interpretability methods is a challenging task that is necessary to extend the use of AI among clinicians. In this work, we propose a novel methodology to quantify the similarity between the decision rules used by a DL model and an ophthalmologist, based on the assumption that doctors are more likely to trust a prediction that was based on decision rules they can understand. Given an eye fundus image with OT, the proposed methodology compares the segmentation mask of OT lesions labeled by an ophthalmologist with the attribution matrix produced by interpretability methods. Furthermore, an open dataset that includes the eye fundus images and the segmentation masks is shared with the community. The proposal was tested on three different DL architectures. The results suggest that complex models tend to perform worse in terms of likelihood to be trusted while achieving better results in sensitivity and specificity.
Information Generating Function of Ranked Set Samples
Authors: Kharazmi Omid , Tamandi Mostafa , Balakrishnan Narayanaswamy
Published: October 2021

In the present paper, we study the information generating (IG) function and relative information generating (RIG) function measures associated with maximum and minimum ranked set sampling (RSS) schemes with unequal sizes. We also examine the IG measures for simple random sampling (SRS) and provide some comparison results between SRS and RSS procedures in terms of dispersive stochastic ordering. Finally, we discuss the RIG divergence measure between SRS and RSS frameworks.
Students and Teachers Using Mentimeter: Technological Innovation to Face the Challenges of the COVID-19 Pandemic and Post-Pandemic in Higher Education
Authors: Pichardo J. Ignacio , López-Medina Esteban F. , Mancha-Cáceres Olga , González-Enríquez Isabel , Hernández-Melián Alejandro , Blázquez-Rodríguez Maribel , Jiménez Virginia , Logares Marina , Carabantes-Alarcon David , Ramos-Toro Mónica , Isorna Esther , Cornejo-Valle Mónica , Borrás-Gené Oriol
Published: October 2021

The COVID-19 pandemic has prompted higher university lecturers to develop their digital skills in order to adapt to online teaching. A group of university teachers decided to evaluate the educational uses of Mentimeter to promote student participation and active learning. A questionnaire was answered by 400 students and 12 participating academics. These 12 academic respondents also participated in a focus group after experiencing this software during an academic course. Qualitative and quantitative data was collected and analyzed to conclude that this software not only facilitated student participation during the pandemic (both face-to-face and online) in synchronous and asynchronous ways but also improved attention, engagement, collaborative learning and interaction. Immediate feedback made it possible for teachers to monitor the students’ learning processes and to adjust the content and pace accordingly. Students and educators highlighted the inclusive potential of this tool, as it allows participation from a diverse audience with different backgrounds and capacities, ensuring inclusive and equitable education for all. Some opportunities for improvement were also identified, namely more functions to make the software more attractive and adapt it to different educational objectives.
Design of a Compact Ultra-Wideband Bandpass Filter Using Inductively Compensated Parallel-Coupled Lines
Authors: Jamsai Meechai , Angkawisittpan Niwat , Nuan-On Adisorn
Published: October 2021

An ultra-wideband bandpass filter (UWB-BPF) using inductively compensated parallel-coupled lines (ICPCL) is presented in this article. It consists of three circuits: a high-pass filter (HPF), a lowpass filter (LPF), and a transmission line. The HPF and the LPF are independently synthesized from the ICPCL. The proposed filter can suppress unwanted frequencies in the upper stopband and increase the skirt slope of the frequency response in the transition bands. The fabricated UWB-BPF with compact size provides good passband performances, with insertion loss of better than −0.49 dB and return loss of better than −12 dB in the frequency range of 2.92–10.95 GHz (the bandwidth of 8.03 GHz). The 107% bandwidth is achieved. In addition, the proposed filter can suppress the spurious frequencies at 2f0, which is greater than 30 dB. The measured results accord well with the simulation results. The novelty of the paper is the introduction of the ICPCL for the construction of the compact UWB-BPF.
Energy Management in the Railway Industry: A Case Study of Rail Freight Carrier in Poland
Authors: Kuzior Aleksandra , Staszek Marek
Published: October 2021

Energy is crucial to economic development, but its production usually has a negative impact on the environment. This ambivalence leads to the need for methods to improve energy efficiency. Transportation is one of the largest global energy consumers. Therefore, improving the energy efficiency of transportation is crucial for sustainable development. The aim of this article is to show the limitations of energy management in railways, resulting from the model of market regulation. The question in this context is whether only technological methods can be used in railways to steer its energy efficiency, as is suggested by the existing research. Critical analysis, desk research and a case study of Polish railway undertaking were used to find an answer to the research question. The discussion of the results shows that the European regulatory system leads to greater complications in the field of energy management than in other global regions, where railways are also important for the economy. Due to these limitations, rail operators use indirect methods to measure energy efficiency. Results indicate that although energy efficiency improvements are being achieved, they are mainly due to organizational measures and not technological ones as could be expected based on previous research.
Quality and Delivery Costs of Wood Chips by Railway vs. Road Transport
Authors: Stolarski Mariusz Jerzy , Stachowicz Paweł , Sieniawski Waldemar , Krzyżaniak Michał , Olba-Zięty Ewelina
Published: October 2021

Forests are the main sources of wood chips delivered to the end customers by road or railway. This research analysed the impact of the quarter of the year: Q1 (January–March), Q2 (April–June), Q3 (July–September), Q4 (October–December) when wood chips were obtained over two consecutive years (2019–2020) and the type of transport used (railway and road) on the thermophysical properties of wood chips and the cost of their delivery. The mean moisture content in the wood chips was 38.28% and it was the highest (45.55%) in Q1, while in Q2 and Q3, this parameter was 8 and 17 percentage points (p.p.) lower. The mean lower heating value (LHV) of the chips was 10.46 GJ Mg−1. The chips delivered by road transport had a 4% higher LHV compared to those shipped by railway transport. The wood chips contained 3.42% d.m. of ash. The road transport at a distance of 200 km was found to be approximately 10% cheaper compared to the transport by rail for most of the study period, both with respect to 1 Mg of fresh or dry mass and 1 GJ of energy in the chips. The railway transport was cheaper in the winter (Q1).
Research on Early Warning for Gas Risks at a Working Face Based on Association Rule Mining
Authors: Huang Yuxin , Fan Jingdao , Yan Zhenguo , Li Shugang , Wang Yanping
Published: October 2021

In the process of gas prediction and early warning, outliers in the data series are often discarded. There is also a likelihood of missing key information in the analysis process. To this end, this paper proposes an early warning model of coal face gas multifactor coupling relationship analysis. The model contains the k-means algorithm based on initial cluster center optimization and an Apriori algorithm based on weight optimization. Optimizing the initial cluster center of all data is achieved using the cluster center of the preorder data subset, so as to optimize the k-means algorithm. The optimized algorithm is used to filter out the outliers in the collected data set to obtain the data set of outliers. Then, the Apriori algorithm is optimized so that it can identify more important information that appears less frequently in the events. It is also used to mine and analyze the association rules of abnormal values and obtain interesting association rule events among the gas outliers in different dimensions. Finally, four warning levels of gas risk are set according to different confidence intervals, the truth and reliable warning results are obtained. By mining association rules between abnormal data in different dimensions, the validity and effectiveness of the gas early warning model proposed in this paper are verified. Realizing the classification of early warning of gas risks has important practical significance for improving the safety of coal mines.
Monitoring of Solar Still Desalination System Using the Internet of Things Technique
Authors: Benghanem Mohamed , Mellit Adel , Emad Mohammed , Aljohani Abdulaziz
Published: October 2021

In this work, a smart solar still prototype for water desalination is designed. It consists of a basic solar still, a solar preheater and a remote monitoring system based on the Internet of Things (IoT) technique. The monitoring system is developed and integrated into the hybrid solar still in order to control its evolution online, as well the quality of the freshwater provided by checking measured parameters such as pH. Thanks to the IoT technique, parameters collected by the monitoring system (e.g., air temperatures, relative humidity, etc.) are uploaded to the cloud for online remote monitoring. The users are notified by an SMS about the status of the system (e.g., water level in the basin, water in the tank, etc.), using an GSM module. The whole system, including the preheater, water pump, valve, sensors and an electronic board, is powered by a photovoltaic module of 75 Wp. The results showed that by adding a solar preheater system, the evaporation process is accelerated and, consequently, the daily yield is improved and reaches the value of 12.165 L/m2/day. The saline concentration of the tested ground water is 3.9 g/Kg (0.39%), and, after desalination, the salinity is 0.1 g/Kg (0.01%).
Formation of Graphite-Copper/N-Silicon Schottky Photovoltaic Diodes Using Different Plasma Technologies
Authors: Kavaliauskas Žydrūnas , Dovydaitis Vilius , Kėželis Romualdas , Marcinauskas Liutauras , Valinčius Vitas , Baltušnikas Arūnas , Iljinas Aleksandras , Gecevičius Giedrius , Čapas Vytautas
Published: October 2021

Plasma spraying and magnetron sputtering were used to form graphite–copper films on an n-type silicon surface. The main objective of this work was to compare the properties of the obtained graphite–copper Schottky photodiodes prepared using two different layer formation methods and to evaluate the influence of copper content on the surface morphology, phase structure, and photovoltaic characteristics of the graphite–copper films. Surface morphology analysis shows that the surface of the formed layers using either plasma spraying technology or the magnetron sputtering method consists of various sphere-shaped microstructures. The X-ray diffraction measurements demonstrated that the graphite–copper coatings formed by plasma spraying were crystalline phase. Meanwhile, the films deposited by magnetron sputtering were amorphous when the copper concentration was up to 9.7 at.%. The increase in copper content in the films led to the formation of Cu crystalline phase. Schottky diodes formed using magnetron sputtering technology had a maximum current density of 220 mA/cm2 at 5 V. Meanwhile, the maximum electric current density of Schottky photodiodes formed using plasma spraying reached 3.8 mA/cm2. It was demonstrated that the efficiency of Schottky diodes formed using magnetron sputtering was up to 60 times higher than Schottky diodes formed using plasma spraying.
Equivalent Impedance Calculation Method for Control Stability Assessment in HVDC Grids
Authors: Loku Fisnik , Düllmann Patrick , Brantl Christina , Monti Antonello
Published: October 2021

A major challenge in the development of multi-vendor HVDC networks are converter control interactions. While recent publications have reported interoperability issues such as persistent oscillations for first multi-vendor HVDC setups with AC-side coupling, multi-terminal HVDC networks are expected to face similar challenges. To investigate DC-side control interactions and mitigate possible interoperability issues, several methods based on the converters’ and DC network’s impedances have been proposed in literature. For DC network’s impedance modelling, most methods require detailed knowledge of all converters’ design and controls. However, in multi-vendor HVDC networks, converter control parameters are not expected to be shared due to proprietary reasons. Therefore, to facilitate impedance-based stability analyses in multi-vendor MTDC networks, methods that do not require the disclosure of the existing converter controls are needed. Here, detailed impedance measurements can be applied; however, they are time-consuming and require new measurement for a single configuration change. This paper proposes an equivalent impedance calculation method suitable for multi-vendor DC networks, which for available black-box models or converter impedance characteristics can be modularly applied for various network configurations, including different control settings and operating points, while significantly reducing the required time for obtaining an equivalent DC network impedance.