bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Extracellular Vesicles Play a Role in Immune System Modulation in Minimal Hepatic Encephalopathy
Authors: Gallego Juan José , Fiorillo Alessandra , Casanova-Ferrer Franc , Urios Amparo , Ballester María-Pilar , Durbán Lucia , Megías Javier , Rubio Teresa , Cabrera-Pastor Andrea , Escudero-García Desamparados , Felipo Vicente , Montoliu Carmina
Published: October 2022

Minimal hepatic encephalopathy (MHE) is associated with changes in the immune system including an increased pro-inflammatory environment and altered differentiation of CD4+ T lymphocytes. The mechanisms remain unknown. Changes in extracellular vesicle (EV) cargo including proteins and miRNAs could play a main role as mediators of immune system changes associated with MHE. The aim was to assess whether plasma EVs from MHE patients played a role in inducing the pro-inflammatory environment and altered differentiation of CD4+ T lymphocyte subtypes in MHE patients. We characterized the miRNA and protein cargo of plasma EVs from 50 cirrhotic patients (27 without and 23 with MHE) and 24 controls. CD4+ T cells from the controls were cultured with plasma EVs from the three groups of study, and the cytokine release and differentiation to CD4+ T-cell subtypes were assessed. Plasma EVs from MHE patients had altered miRNA and protein contents, and were enriched in inflammatory factors compared to the controls and patients without MHE. EVs from MHE patients modulated the expression of pro-inflammatory IL-17, IL-21, and TNF-α and anti-inflammatory TGF-β in cultured CD4+ T lymphocytes, and increased the proportion of Th follicular and Treg cells and the activation of Th17 cells. In conclusion, plasma EVs could play an important role in the induction of immune changes observed in MHE.
ATP8B1 Deficiency Results in Elevated Mitochondrial Phosphatidylethanolamine Levels and Increased Mitochondrial Oxidative Phosphorylation in Human Hepatoma Cells
Authors: Gómez-Mellado Valentina E. , Chang Jung-Chin , Ho-Mok Kam S. , Bernardino Morcillo Carmen , Kersten Remco H. J. , Oude Elferink Ronald P. J. , Verhoeven Arthur J. , Paulusma Coen C.
Published: October 2022

ATP8B1 is a phospholipid flippase that is deficient in patients with progressive familial intrahepatic cholestasis type 1 (PFIC1). PFIC1 patients suffer from severe liver disease but also present with dyslipidemia, including low plasma cholesterol, of yet unknown etiology. Here we show that ATP8B1 knockdown in HepG2 cells leads to a strong increase in the mitochondrial oxidative phosphorylation (OXPHOS) without a change in glycolysis. The enhanced OXPHOS coincides with elevated low-density lipoprotein receptor protein and increased mitochondrial fragmentation and phosphatidylethanolamine levels. Furthermore, expression of phosphatidylethanolamine N-methyltransferase, an enzyme that catalyzes the conversion of mitochondrial-derived phosphatidylethanolamine to phosphatidylcholine, was reduced in ATP8B1 knockdown cells. We conclude that ATP8B1 deficiency results in elevated mitochondrial PE levels that stimulate mitochondrial OXPHOS. The increased OXPHOS leads to elevated LDLR levels, which provides a possible explanation for the reduced plasma cholesterol levels in PFIC1 disease.
Hepatobiliary Thyroid Hormone Deficiency Impacts Bile Acid Hydrophilicity and Aquaporins in Cholestatic C57BL/6J Mice
Authors: Kube Irina , Kowalczyk Manuela , Hofmann Ute , Ghallab Ahmed , Hengstler Jan Georg , Führer Dagmar , Zwanziger Denise
Published: October 2022

Women are more prone to develop either hypothyroidism or cholesterol gallstones than men. However, a male predominance in cholesterol gallstones under hypothyroidism was reported. Recently, a novel pathogenic link between thyroid hormone (TH) deficiency and cholesterol gallstones has been described in male mice. Here, we investigate if TH deficiency impacts cholesterol gallstone formation in females by the same mechanism. Three-month-old C57BL/6J mice were randomly divided into a control, a TH deficient, a lithogenic, and a lithogenic + TH deficient group and diet-treated for two, four, and six weeks. Gallstone prevalence, liver function tests, bile composition, hepatic gene expression, and gallbladder aquaporin expression and localization were investigated. Cholesterol gallstones were observed in lithogenic + TH deficient but not lithogenic only female mice. Diminished hydrophilicity of primary bile acids due to decreased gene expression of hepatic detoxification phase II enzymes was observed. A sex-specific expression and localization of hepatobiliary aquaporins involved in transcellular water and glycerol permeability was observed under TH deficient and lithogenic conditions. TH deficiency promotes cholesterol gallstone formation in female C57BL/6J mice by the same mechanism as observed in males. However, cholesterol gallstone prevalence was lower in female than male C57BL/6J mice. Interestingly, the sex-specific expression and localization of hepatobiliary aquaporins could protect female C57BL/6J mice to cholestasis and could reduce biliary water transport in male C57BL/6J mice possibly contributing to the sex-dependent cholesterol gallstone prevalence under TH deficiency.
A Novel Antibody-Drug Conjugate Targeting Nectin-2 Suppresses Ovarian Cancer Progression in Mouse Xenograft Models
Authors: Sim Yun Hee , Um Yun Jung , Park Jeong-Yang , Seo Min-Duk , Park Sang Gyu
Published: October 2022

Ovarian cancer is the fifth leading cause of cancer, followed by front line is mostly platinum agents and PARP inhibitors, and very limited option in later lines. Therefore, there is a need for alternative therapeutic options. Nectin-2, which is overexpressed in ovarian cancer, is a known immune checkpoint that deregulates immune cell function. In this study, we generated a novel anti-nectin-2 antibody (chimeric 12G1, c12G1), and further characterized it using epitope mapping, enzyme-linked immunosorbent assay, surface plasmon resonance, fluorescence-activated cell sorting, and internalization assays. The c12G1 antibody specifically bound to the C2 domain of human nectin-2 with high affinity (KD = 2.90 × 10−10 M), but not to mouse nectin-2. We then generated an antibody-drug conjugate comprising the c12G1 antibody conjugated to DM1 and investigated its cytotoxic effects against cancer cells in vitro and in vivo. c12G1-DM1 induced cell cycle arrest at the mitotic phase in nectin-2-positive ovarian cancer cells, but not in nectin-2-negative cancer cells. c12G1-DM1 induced ~100-fold cytotoxicity in ovarian cancer cells, with an IC50 in the range of 0.1 nM~7.4 nM, compared to normal IgG-DM1. In addition, c12G1-DM1 showed ~91% tumor growth inhibition in mouse xenograft models transplanted with OV-90 cells. These results suggest that c12G1-DM1 could be used as a potential therapeutic agent against nectin-2-positive ovarian cancers.
The Effects of Genistein at Different Concentrations on MCF-7 Breast Cancer Cells and BJ Dermal Fibroblasts
Authors: Pawlicka Magda Aleksandra , Zmorzyński Szymon , Popek-Marciniec Sylwia , Filip Agata Anna
Published: October 2022

This study aimed to evaluate the safety and potential use of soy isoflavones in the treatment of skin problems, difficult-to-heal wounds and postoperative scars in women after the oncological treatment of breast cancer. The effects of different concentrations of genistein as a representative of soy isoflavonoids on MCF-7 tumor cells and BJ skin fibroblasts cultured in vitro were assessed. Genistein affects both healthy dermal BJ fibroblasts and cancerous MCF-7 cells. The effect of the tested isoflavonoid is closely related to its concentration. High concentrations of genistein destroy MCF-7 cancer cells, regardless of the exposure time, with a much greater effect on reducing cancer cell numbers at longer times (48 h). Lower concentrations of genistein (10 and 20 μM) increase the abundance of dermal fibroblasts. However, higher concentrations of genistein (50 μM and higher) are detrimental to fibroblasts at longer exposure times (48 h). Our studies indicate that although genistein shows high potential for use in the treatment of skin problems, wounds and surgical scars in women during and after breast cancer treatment, it is not completely safe. Introducing isoflavonoids to treatment requires further research into their mechanisms of action at the molecular level, taking into account genetic and immunological aspects. It is also necessary to conduct research in in vivo models, which will allow for eliminating adverse side effects of therapy.
Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease
Authors: Ivanušec Adrijan , Šribar Jernej , Leonardi Adrijana , Zorović Maja , Živin Marko , Križaj Igor
Published: October 2022

Alzheimer’s disease (AD), a progressive form of dementia, is characterized by the increased expression of secreted phospholipase A2 group IIA (GIIA) in the affected tissue and the dysfunction of neuronal mitochondria, similar to that induced by an orthologous GIIA from snake venom, β-neurotoxic ammodytoxin (Atx), in the motor neurons. To advance our knowledge about the role of GIIA in AD, we studied the effect of rat GIIA on the neuronal mitochondria and compared it with that of the Atx. We produced recombinant rat GIIA (rGIIA) and its enzymatically inactive mutant, rGIIA(D49S), and demonstrated that they interact with the subunit II of cytochrome c oxidase (CCOX-II) as Atx. rGIIA and rGIIA(D49S) bound to this essential constituent of the respiratory chain complex with an approximately 100-fold lower affinity than Atx; nevertheless, both rGIIA molecules potently inhibited the CCOX activity in the isolated rat mitochondria. Like Atx, rGIIA was able to reach the mitochondria in the PC12 cells from the extracellular space, independent of its enzymatic activity. Consistently, the inhibition of the CCOX activity in the intact PC12 cells and in the rat’s brain tissue sections was clearly demonstrated using rGIIA(D49S). Our results show that the effects of mammalian and snake venom β-neurotoxic GIIA on the neuronal mitochondria have similar molecular backgrounds. They suggest that the elevated extracellular concentration of GIIA in the AD tissue drives the translocation of this enzyme into local neurons and their mitochondria to inhibit the activity of the CCOX in the respiratory chain. Consequently, the process of oxidative phosphorylation in the neurons is attenuated, eventually leading to their degeneration. Atx was thus revealed as a valuable molecular tool for further investigations of the role of GIIA in AD.
DNA Penetration into a Lysozyme Layer at the Surface of Aqueous Solutions
Authors: Chirkov Nikolay S. , Lin Shi-Yow , Michailov Alexander V. , Miller Reinhard , Noskov Boris A.
Published: October 2022

The interactions of DNA with lysozyme in the surface layer were studied by performing infrared reflection–absorption spectroscopy (IRRAS), ellipsometry, surface tensiometry, surface dilational rheology, and atomic force microscopy (AFM). A concentrated DNA solution was injected into an aqueous subphase underneath a spread lysozyme layer. While the optical properties of the surface layer changed fast after DNA injection, the dynamic dilational surface elasticity almost did not change, thereby indicating no continuous network formation of DNA/lysozyme complexes, unlike the case of DNA interactions with a monolayer of a cationic synthetic polyelectrolyte. A relatively fast increase in optical signals after a DNA injection under a lysozyme layer indicates that DNA penetration is controlled by diffusion. At low surface pressures, the AFM images show the formation of long strands in the surface layer. Increased surface compression does not lead to the formation of a network of DNA/lysozyme aggregates as in the case of a mixed layer of DNA and synthetic polyelectrolytes, but to the appearance of some folds and ridges in the layer. The formation of more disordered aggregates is presumably a consequence of weaker interactions of lysozyme with duplex DNA and the stabilization, at the same time, of loops of unpaired nucleotides at high local lysozyme concentrations in the surface layer.
Quenching of Protein Fluorescence by Fullerenol C60(OH)36 Nanoparticles
Authors: Lichota Anna , Szabelski Mariusz , Krokosz Anita
Published: October 2022

The effect of the interaction between fullerenol C60(OH)36 (FUL) and alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae and human serum albumin (HSA) was studied by absorption spectroscopy, fluorescence spectroscopy, and time-resolved fluorescence spectroscopy. As shown in the study, the fluorescence intensities of ADH and HSA at excitation wavelengths λex = 280 nm (Trp, Tyr) and λex = 295 nm (Trp) are decreased with the increase in the FUL concentration. The results of time-resolved measurements indicate that both quenching mechanisms, dynamic and static, are present. The binding constant Kb and the number of binding sites were obtained for HSA and ADH. Thus, the results indicated the formation of FUL complexes and proteins. However, the binding of FUL to HSA is much stronger than that of ADH. The transfer of energy from the protein to FUL was also proved.
PD-BertEDL: An Ensemble Deep Learning Method Using BERT and Multivariate Representation to Predict Peptide Detectability
Authors: Wang Huiqing , Wang Juan , Feng Zhipeng , Li Ying , Zhao Hong
Published: October 2022

Peptide detectability is defined as the probability of identifying a peptide from a mixture of standard samples, which is a key step in protein identification and analysis. Exploring effective methods for predicting peptide detectability is helpful for disease treatment and clinical research. However, most existing computational methods for predicting peptide detectability rely on a single information. With the increasing complexity of feature representation, it is necessary to explore the influence of multivariate information on peptide detectability. Thus, we propose an ensemble deep learning method, PD-BertEDL. Bidirectional encoder representations from transformers (BERT) is introduced to capture the context information of peptides. Context information, sequence information, and physicochemical information of peptides were combined to construct the multivariate feature space of peptides. We use different deep learning methods to capture the high-quality features of different categories of peptides information and use the average fusion strategy to integrate three model prediction results to solve the heterogeneity problem and to enhance the robustness and adaptability of the model. The experimental results show that PD-BertEDL is superior to the existing prediction methods, which can effectively predict peptide detectability and provide strong support for protein identification and quantitative analysis, as well as disease treatment.
Identification of the NAC Transcription Factors and Their Function in ABA and Salinity Response in Nelumbo nucifera
Authors: Zhao Shuping , Jiang Tao , Zhang Yao , Zhang Kailing , Feng Kai , Wu Peng , Li Liangjun
Published: October 2022

Nelumbo nucifera Gaertn. is an important perennial aquatic herb that has high ornamental, edible, medicinal, and economic value, being widely distributed and used in China. The NAC superfamily (NAM, ATAF1/2, CUC2) plays critical roles in plant growth, development, and response to abiotic and biotic stresses. Though there have been a few reports about NAC genes in lotus, systematic analysis is still relatively lacking. The present study aimed to characterize all the NAC genes in the lotus and obtain better insights on the NnNACs in response to salt stress by depending on ABA signaling. Here, 97 NAC genes were identified by searching the whole lotus genome based on the raw HMM models of the conserved NAM domain and NAC domain. They were characterized by bioinformatics analysis and divided into 18 subgroups based on the phylogenetic tree. Cis-element analysis demonstrated that NAC genes are responsive to biotic and abiotic stresses, light, low temperature, and plant hormones. Meanwhile, NAC genes had tissue expression specificity. qRT-PCR analysis indicated that NAC genes could be upregulated or downregulated by NaCl treatment, ABA, and fluoridone. In addition, NAC016, NAC025, and NAC070, whose encoding genes were significantly induced by NaCl and ABA, were located in the nucleus. Further analysis showed the three NAC proteins had transcriptional activation capabilities. The co-expression network analysis reflected that NAC proteins may form complexes with other proteins to play a role together. Our study provides a theoretical basis for further research to be conducted on the regulatory mechanisms of salinity resistance in the lotus.
Meta-Analysis of the Public RNA-Seq Data of the Western Honeybee Apis mellifera to Construct Reference Transcriptome Data
Authors: Yokoi Kakeru , Wakamiya Takeshi , Bono Hidemasa
Published: October 2022

The Western honeybee (Apis mellifera) is valuable in biological research and agriculture. Its genome sequence was published before those for other insect species. RNA-Seq data for A. mellifera have been applied in several recently published studies. Nevertheless, these data have not been prepared for use in subsequent meta-analyses. To promote A. mellifera transcriptome analysis, we constructed reference transcriptome data using the reference genome sequence and RNA-Seq data curated from about 1,000 runs of public databases. The new reference transcriptome data construct comprised 149,685 transcripts, and 194,174 protein sequences were predicted. Approximately 50–60% of the predicted protein sequences were functionally annotated using the protein sequence data for several model and insect species. Novel candidate immune-related transcripts were searched by meta-analysis using immune-response-related RNA-Seq and reference transcriptome data. Three to twenty candidate transcripts including autophagy-related protein 3 were upregulated or downregulated in response to both viral and bacterial infections. The constructed reference transcriptome data may facilitate future transcriptome analyses of A. mellifera.
The CMS Level-1 Calorimeter Trigger for the HL-LHC
Authors: Kumar Piyush , Gomber Bhawna
Published: October 2022

The High-Luminosity LHC (HL-LHC) provides an opportunity for a pioneering physics program to harness an integrated luminosity of 4000 fb−1 of ten years of operations. This large volume of collision data will help in high precision measurements of the Standard Model (SM) and the search for new and rare physics phenomena. The harsh environment of 200 proton–proton interactions poses a substantial challenge in the collection of these large datasets. The HL-LHC CMS Level-1 (L1) trigger, including the calorimeter trigger, will receive a massive upgrade to tackle the challenge of a high-bandwidth and high pileup environment. The L1 trigger is planned to handle a very high bandwidth (∼63 Tb/s) with an output rate of 750 kHz, and the desired latency budget is 12.5 μs. The calorimeter trigger aims to process the high-granular information from the new end-cap detector called the high-granularity calorimeter (HGCAL) and the barrel calorimeter. The HL-LHC trigger prototyped boards are equipped with large modern-day FPGAs and high-speed optical links (∼28 Gb/s), which helps in the parallel and rapid computation of the calorimeter trigger algorithms. This article discusses the proposed design and expected performance of the upgraded CMS Level-1 calorimeter trigger system.
Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation—A Propensity Score-Matched Multicenter Cohort Study
Authors: Pasin Laura , Gregori Dario , Pettenuzzo Tommaso , De Cassai Alessandro , Boscolo Annalisa , Sella Nicolò , Lorenzoni Giulia , Geraldini Federico , Pistollato Elisa , Ranieri Vito Marco , Landoni Giovanni , Rosi Paolo , Navalesi Paolo ,   COVID-19 VENETO ICU Network
Published: October 2022

The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV (“straight intubation”). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the “straight intubation” group and the “NIV” group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.
Should Reward Deficiency Syndrome (RDS) Be Considered an Umbrella Disorder for Mental Illness and Associated Genetic and Epigenetic Induced Dysregulation of Brain Reward Circuitry?
Authors: Blum Kenneth , Dennen Catherine A. , Elman Igor , Bowirrat Abdalla , Thanos Panayotis K. , Badgaiyan Rajendra D. , Downs B. William , Bagchi Debasis , Baron David , Braverman Eric R. , Gupta Ashim , Green Richard , McLaughlin Thomas , Barh Debmalya , Gold Mark S.
Published: October 2022

Reward Deficiency Syndrome (RDS) is defined as a breakdown of reward neurotransmission that results in a wide range of addictive, compulsive, and impulsive behaviors. RDS is caused by a combination of environmental (epigenetic) influences and DNA-based (genetic) neurotransmission deficits that interfere with the normal satisfaction of human physiological drives (i.e., food, water, and sex). An essential feature of RDS is the lack of integration between perception, cognition, and emotions that occurs because of (1) significant dopaminergic surges in motivation, reward, and learning centers causing neuroplasticity in the striato-thalamic-frontal cortical loop; (2) hypo-functionality of the excitatory glutamatergic afferents from the amygdala–hippocampus complex. A large volume of literature regarding the known neurogenetic and psychological underpinnings of RDS has revealed a significant risk of dopaminergic gene polymorphic allele overlap between cohorts of depression and subsets of schizophrenia. The suggestion is that instead of alcohol, opioids, gambling disorders, etc. being endophenotypes, the true phenotype is RDS. Additionally, reward deficiency can result from depleted or hereditary hypodopaminergia, which can manifest as a variety of personality traits and mental/medical disorders that have been linked to genetic studies with dopamine-depleting alleles. The carrying of known DNA antecedents, including epigenetic insults, results in a life-long vulnerability to RDS conditions and addictive behaviors. Epigenetic repair of hypodopaminergia, the causative basis of addictive behaviors, may involve precision DNA-guided therapy achieved by combining the Genetic Addiction Risk Severity (GARS) test with a researched neutraceutical having a number of variant names, including KB220Z. This nutraceutical formulation with pro-dopamine regulatory capabilities has been studied and published in peer-reviewed journals, mostly from our laboratory. Finally, it is our opinion that RDS should be given an ICD code and deserves to be included in the DSM-VI because while the DSM features symptomology, it is equally important to feature etiological roots as portrayed in the RDS model.
Endotracheal Intubation Using C-MAC Video Laryngoscope vs. Direct Laryngoscope While Wearing Personal Protective Equipment
Authors: Kim Da Saem , Jeong Daun , Park Jong Eun , Lee Gun Tak , Shin Tae Gun , Chang Hansol , Kim Taerim , Lee Se Uk , Yoon Hee , Cha Won Chul , Sim Yong Jin , Park Song Yi , Hwang Sung Yeon
Published: October 2022

This study sought to determine whether the C-MAC video laryngoscope (VL) performed better than a direct laryngoscope (DL) when attempting endotracheal intubation (ETI) in the emergency department (ED) while wearing personal protective equipment (PPE). This was a retrospective single-center observational study conducted in an academic ED between February 2020 and March 2022. All emergency medical personnel who participated in any ETI procedure were required to wear PPE. The patients were divided into the C-MAC VL group and the DL group based on the device used during the first ETI attempt. The primary outcome measure was the first-pass success (FPS) rate. A multiple logistic regression was used to determine the factors associated with FPS. Of the 756 eligible patients, 650 were assigned to the C-MAC group and 106 to the DL group. The overall FPS rate was 83.5% (n = 631/756). The C-MAC group had a significantly higher FPS rate than the DL group (85.7% vs. 69.8%, p < 0.001). In the multivariable logistic regression analysis, C-MAC use was significantly associated with an increased FPS rate (adjusted odds ratio, 2.86; 95% confidence interval, 1.69–4.08; p < 0.001). In this study, we found that the FPS rate of ETI was significantly higher when the C-MAC VL was used than when a DL was used by emergency physicians constrained by cumbersome PPE.
Tumour-Related Parameters as a Prognostic Factor in Patients with Advanced Cervical Cancer: 20-Year Follow-Up of Diagnostic and Treatment Changes during Chemioradiotherapy
Authors: Warenczak-Florczak Zaneta , Burchardt Ewa , Wilk Agnieszka , Roszak Andrzej
Published: October 2022

Concurrent radiochemotherapy (RCHT) has been the standard treatment for locally advanced cervical cancer since 1999. During this 20-year period, both diagnostic and radiotherapy techniques have developed, such as positron emission tomography (PET) or brachytherapy (BT) planning. The aim of the study was to assess the relationships between prognostic factors and the results of treatment in patients with advanced cervical cancer independent of these changes. The analysis included 266 patients with stage IIB or IIIB FIGO 2009 cervical cancer divided into two groups: one including 147 patients diagnosed with physical examination and ultrasonography (USG) and treated with RCHT with 2D BT from 2001 to 2005; another including 119 patients with metastatic pelvic lymph node diagnosed with PET and treated from 2010 to 2016 with RCHT and 3D BT. The mean five-year overall survival (OS) rate was 59.2% in the first vs. 65.5% in the second group (p = 0.048). However, in both groups, stage IIB patients had a significantly higher 5-year OS rate, despite the presence of nodal metastases in group 2. In the first group it was 75.1% in IIB vs. 54.8% in IIIB (p = 0.040) 5-year OS and 77.5% vs. 55.8% (p = 0.034) in the second group. Important was also a significant association between the dose of BT and survival in group 2: 45.7% vs. 69.2% for dose <28 Gy and 28 Gy (p = 0.018). Evolution in the diagnosis and treatment of patients with cervical cancer had led to improvement in the survival of patients and precise treatment with an appropriate stage assessment. However local advance of the tumour is still the most important prognostic factor.
The Stages and Grades of Periodontitis Are Risk Indicators for Peri-Implant Diseases—A Long-Term Retrospective Study
Authors: Yamazaki Mikiko , Yamazaki Kosaku , Baba Yuh , Ito Hiroshi , Loos Bruno G. , Takahashi Keiso
Published: October 2022

The aim of this study is to evaluate the factors of implant failure in patients with periodontitis and their impact on the prognosis of having a peri-implant disease and/or implant failure. Data regarding 325 implants among 84 patients with periodontitis were retrospectively examined. Patients were classified by Stage (I, II, III, IV) and Grade (A, B, C), implant failures for peri-implant disease and lack of osseointegration. Clinical data, including implant- and patient-related variables were evaluated by principal components analysis (PCA) and two-step cluster analysis (CA). Survival and success rates were 96.3% and 87.1%, respectively. Prevalence of peri-implant disease was significantly higher in Stage IV patients (p < 0.05), and incidence of lost implant due to peri-implantitis was significantly higher in patients with bone augmentation (BA) (p < 0.05). PCA and CA revealed five of eleven variables and four clusters at patient level, and six of fourteen variables and three clusters at implant level. Stage and Grade are useful indicators for the development of peri-implant diseases in which BA and the number of implants are involved.
Metabolomic Signatures of Autism Spectrum Disorder
Authors: Brister Danielle , Rose Shannon , Delhey Leanna , Tippett Marie , Jin Yan , Gu Haiwei , Frye Richard
Published: October 2022

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis.
Do the Underlying Portfolios Matter? A Comparative Study of Equity-Linked Pay-at-Maturity Principal Protected Notes in Canada and the UK
Authors: Li Yuanshun , Anderson Scott , McGraw Patricia A.
Published: October 2022

This study examines the relationship between the return and the holding cost of equity-linked pay-at-maturity principal protected notes (EL-PAM-PPNs) and the mean return and volatility of the underlying portfolio using 1568 EL-PAM-PPNs issued in the UK and Canada between 2003 and 2015. We find that: (i) the underlying portfolio’s mean return decreases the note holding cost; (ii) the underlying portfolio’s volatility increases the note return and decreases the note holding cost; (iii) investors could maximize note return and minimize holding costs by choosing EL-PAM-PPNs prudently. Investors in both countries should purchase notes with higher participation rates, where the underlying portfolio contains a higher number of stocks and lower expected volatility. UK investors should avoid callable notes and choose notes with a longer time to maturity, where payoff is determined by a single observation of the underlying portfolio’s value at maturity. Surprisingly, Canadian investors should choose callable notes and notes with a shorter time to maturity, where payoff is determined by the average of multiple observations of the underlying portfolio’s value over the life of the note. They should also look for notes that include a guaranteed positive return, and where the underlying asset has a higher dividend yield.
Analysis of landslide Susceptibility and Tree Felling Due to an Extreme Event at Mid-Latitudes: Case Study of Storm Vaia, Italy
Authors: Antonetti Guido , Gentilucci Matteo , Aringoli Domenico , Pambianchi Gilberto
Published: October 2022

Storm Vaia on 29 October 2018, hit northeastern Italy and produced extensive damage in the immediacy of the event, including extensive tree felling in some places, as well as debris flow or earth flow landslides. This study aims to assess the susceptibility of the area following extreme events by evaluating the environmental criticality during strong winds and intense precipitation. Specifically, tree felling susceptibility due to wind and landslide susceptibility due mainly to precipitation were analysed by taking into consideration the geomorphological and environmental criticality of the areas under study. In particular, the area was modelled using fluid dynamics software, allowing an understanding of wind accelerations in relation to morphology, showing excellent agreement between the tree falls that occurred during the event and the areas with the highest wind gusts. With regard to landslides, an algorithm was prepared through GIS software that took into account the debris and earth flows that were activated during the extreme event in question, allowing the creation of a susceptibility map that delineated areas of high potential hazard. The final result is a landslide and tree-fall susceptibility map that determines the fragility of the territory during an extreme event. The procedures applied in the study area can be considered as a working method that allows critical values to be obtained for extreme events that can produce damage to the environment and beyond. It follows that this research also has an immediate application purpose by helping the political decision-maker in the choice of interventions to be implemented.
Joining Policy Forums Together to Develop Ki-no-Eki, a Community Currency System for Forest Management in Japan: Dynamics of Policy Communication Networks
Authors: Nakazato Hiromi , Izumi Rui , Lim Seunghoo
Published: October 2022

In some mountainous areas of Japan, the Ki-no-Eki system, in which wood is collected to thin the forest and is exchanged for community currency, has been specifically designed and implemented as a solution to current and emerging forest governance issues. This study aimed to capture the evolutionary processes of a complete communication network consisting of organizations that joined policy forums to help develop the Ki-no-Eki system. A total of 26 policy forums were held from 2011 to 2019 to discuss the adoption and implementation of the Ki-no-Eki system across Japan, and coattendance and the resultant policy discourses among 62 participating Ki-no-Eki organizations in these forums were regarded as dynamic communication network processes. We analyzed how policy communication networks formed and evolved to understand the underlying network dynamics driven by not only endogenous network processes—bonding and bridging social capital—but also exogenous effects defined by actors’ attributes. We employed the stochastic actor-oriented model for network dynamics to manage the collected longitudinal undirected network data. We found (i) the emergence of bonding social capital and (ii) homophilic and heterophilic connections in communication networks, which provided insightful explanations of the driving forces of social cohesion among Ki-no-Eki organizations engaged in forest management in Japan.
Elaboration of Ionic Liquids on the Anti-Wear Performance of the Reinforced Steel-Steel Contact Surface
Authors: Jiang Hua , Hou Xianjun , Ma Yuxin , Guan Weiwei , Liu Haijun , Qian Yucong
Published: October 2022

This study conducted a tribological investigation of base oil (PAO6 and 5W 40) and ionic liquids (IL)-modified lubricants through a four-ball tribometer for 30 min. The lubricants were fabricated via a two-step method using stirring magnetic and ultrasonic dispersion. IL, base oil, and lubricants were, respectively, characterized by XRD and FTIR analysis. In addition, multiple characterizations such as EDS, 3D morphology, and SEM were carried out to evaluate the wear and friction performance of steel balls. Ultimately, the results showed that the coefficient of friction (COF) and wear scar diameter (WSD) of wear scar lubricated by IL-modified lubricants were greatly decreased than that by base oil. IL can well improve the tribological properties of PAO 6 oil and 5W-40 oil due to the tribo-film appearance on the friction surface of wear scar by the effective role of IL. Fascinatingly, this investigation comprehensively and elaborately put a new sight into the lubrication mechanism of how IL reacted with a base oil and enhanced the tribological characteristics.
Investigations on the Frictional Hysteresis Effect of Multi-Leaf Journal Foil Bearing: Modeling, Predictions and Validations
Authors: Li Changlin , Du Jianjun , Li Jie , Xu Zhenni
Published: October 2022

Multi-leaf journal foil bearing (MLJFB) is well known for its applications in the air cycle machines (ACMs) of airplanes. However, its frictional energy dissipation mechanism of overlapped foils has not been theoretically studied and is still not clear to researchers. This paper models the frictional sliding/sticking behaviors between adjacent foil leaves based on the tangent gap, applying the penalty method of contact mechanics. Large foil deformations are calculated to simulate the processes of foil assembly and rotor insertion using nonlinear curve beam elements. Predictions of the frictional hysteresis characteristics of MLJFB are obtained, influenced by foil boundary conditions, leaf number, bearing radial clearance and other foil structural parameters, which correlate well with the test results. This study lays solid theoretical foundations for the static and dynamic research of MLJFB.
5-(1H-Indol-3-yl)-1-methyl-3-phenyl-1,6-benzodiazocin-2(1H)-one
Authors: Belyaeva Kseniya V. , Tomilin Denis N. , Afonin Andrei V. , Trofimov Boris A.
Published: October 2022

The title compound, 5-(1H-indol-3-yl)-1-methyl-3-phenyl-1,6-benzodiazocin-2(1H)-one, was synthesized for the first time by a one-step, two-component reaction between 1-methylbenzimidazole and benzoylindolyl-3-acetylene. The product was characterized by 1H-NMR, 13C-NMR, IR spectroscopy and HRMS.
Correlation of Lack of Fusion Pores with Stress Corrosion Cracking Susceptibility of L-PBF 316L: Effect of Surface Residual Stresses
Authors: Yazdanpanah Arshad , Franceschi Mattia , Rebesan Pietro , Dabalà Manuele
Published: October 2022

Stress corrosion cracking (SCC) of laser powder bed fusion-fabricated 316L was studied under the variation in energy input density to emulate the existence of distinctive types of defects. Various electrochemical polarization measurements were performed in as-received polished and ground states, to elucidate the effect of defect type on corrosion and SCC behaviour in marine solution. The results revealed severe localized corrosion attack and SCC initiation for specimens with a lack of fusion pores (LOF). Moreover, the morphology of SCC was different, highlighting a more dominant effect of selective dissolution of the subgrain matrix for gas porosities and a more pronounced effect of brittle fracture at laser track boundaries for the specimens with LOF pores.
Bond Behavior of Steel Bars in Concrete Confined with Stirrups under Freeze–Thaw Cycles
Authors: Liu Guirong , Dou Xiaoxue , Qu Fulai , Shang Pengran , Zhao Shunbo
Published: October 2022

In order to evaluate the influence of freeze–thaw action on the durability of concrete structures, this paper presented an experimental study to investigate the effects of freezing–thawing cycles and concrete strength on the bond behavior between steel bars and concrete confined with stirrups. Through freeze–thaw cycles and center pullout tests, the failure mode of pullout specimen, concrete strength, mass loss, dynamic elastic modulus, and bond–slip curves were analyzed. At last, the bond–slip constitutive model was proposed for specimens with stirrup confinement under freeze–thaw action. Main test results indicate that the failure mode and shape of bond–slip curves are affected by stirrups. The bond strength hasa certain increase after 100 freeze–thaw cycles owing to the constraining force from stirrups, whereas the splitting tensile strength significantly declines. After 100 freeze–thaw cycles, the splitting tensile strength of C20 and C40 decreased by 40.8% and 46.5%, respectively. The formula was provided to calculate the bond strength of constrained concrete after freeze–thaw cycles, and the damage coefficient and other related parameters in the formula were suggested. The predicted bond–slip curves are close to the experimental results, which could provide reference for the related research of bond performance after freeze–thaw action.
A Suggested Equivalent Method for a Drainage Structure to Analyze Seepage in Tailings Dam
Authors: Zhang Hongwei , Shen Zhenzhong , Liu Detan , Xu Liqun , Gan Lei , Long Yifei
Published: October 2022

To better understand the seepage field in tailings dam with a drainage structure that combines drainage mat, drainage tube, and geotextile, an equivalent seepage analysis method for the drainage structure is presented. In the method, an equivalent drainage structure is suggested to replace the original drainage. It has enough size to be easily presented in the three-dimensional (3d) model of a tailings dam. According to a back analysis procedure using the quasi-3d models of a tailings dam with original and equivalent drainage structures, the material properties of the equivalent drainage structure can be obtained under the principle of drainage capacity equivalence. It is demonstrated that the suggested method is accurate enough to capture the seepage field in a tailings dam based on comparing the calculated and measured phreatic lines in a tailings dam for verification. Then, the method is employed to investigate the seepage field in a tailings dam in China for a case study. The rise of water level, damage of drainage structure, or increase of tailings discharge speed and time will lift up phreatic line. After terminating tailings discharge, phreatic line will first rise and then fall. The effect of tailings discharge on phreatic line will almost disappear after terminating tailings discharge for 24 h.
Bipolar Switching Characteristics of Transparent WOX-Based RRAM for Synaptic Application and Neuromorphic Engineering
Authors: Kim Jihyung , Park Jongmin , Kim Sungjun
Published: October 2022

In this work, we evaluate the resistive switching (RS) and synaptic characteristics of a fully transparent resistive random-access memory (T-RRAM) device based on indium-tin-oxide (ITO) electrodes. Here, we fabricated ITO/WOX/ITO capacitor structure and incorporated DC-sputtered WOX as the switching layer between the two ITO electrodes. The device shows approximately 77% (including the glass substrate) of optical transmittance in visible light and exhibits reliable bipolar switching behavior. The current-voltage (I–V) curve is divided into two types: partial and full curves affected by the magnitude of the positive voltage during the reset process. In the partial curve, we confirmed that the retention could be maintained for more than 104 s and the endurance for more than 300 cycles could be stably secured. The switching mechanism based on the formation/rupture of the filament is further explained through the extra oxygen vacancies provided by the ITO electrodes. Finally, we examined the responsive potentiation and depression to check the synaptic characteristics of the device. We believe that the transparent WOX-based RRAM could be a milestone for neuromorphic devices as well as future non-volatile transparent memory.
In Situ Fabrication and Static Contact Resistance of CdMoO4 Reinforced Cu Matrix Composites
Authors: Li Wei-Jian , Zhang Lu , Chen Zi-Yao , Shao Wen-Zhu , Zhen Liang
Published: October 2022

Particle-reinforced Cu-based electrical contact materials prepared by traditional powder metallurgical methods suffer the same critical problem, where the agglomeration of the addition phases in the Cu matrix significantly deteriorates the performance of the composites and restricts their application. In this work, CdMoO4/Cu matrix composites were fabricated by an in situ method and followed by a powder metallurgical process. Firstly, CdMoO4/particles formed a nucleus and grew up based on the surfaces of Cu particles, realizing the controllable in situ synthesis of mixed powders with homogeneously dispersed CdMoO4 nanoparticles via a one-step reaction. Secondly, the bulk CdMoO4/Cu composites were fabricated by pressing and sintering and then densified by hot-extrusion and cold rolling processes. The microstructures and properties of the extruded and rolled specimens were characterized, respectively. The results indicated that the rolled CdMoO4/Cu composite exhibited excellent comprehensive properties of electrical conductivity and mechanical properties for electrical contact materials. Moreover, the effects of the contact force on the static contact resistance of the extruded and rolled composites were evaluated in the closed state of the contact materials. It was found that the rolled CdMoO4/Cu contact materials possessed a stable electrical contact characteristic with low and steady contact resistance. This work designed ternary CdMoO4 particles to reinforce Cu-based composites with well-balanced performances by an in situ synthesis method and this strategy can be extended to the design of ternary oxide/metal composites utilized as electrical contact materials.
The Research on Anti-Nickel Contamination Mechanism and Performance for Boron-Modified FCC Catalyst
Authors: Yuan Chengyuan , Zhou Lei , Chen Qiang , Su Chengzhuang , Li Zhongfu , Ju Guannan
Published: October 2022

Fluid catalytic cracking (FCC) is still a key process in the modern refining area, in which nickel-contamination for an FCC catalyst could obviously increase the dry gas and coke yields and thus seriously affect the stability of the FCC unit. From the points of surface acidity modification and Ni-passivation, in this paper, a boron-modified FCC catalyst (BM-Cat) was prepared using the in situ addition method with B2O3 as a boron source and emphatically investigated its mechanism and performance of anti-nickel contamination. The mechanism research results suggested that, in calcination, boron could destroy the structure of the Y zeolite and thus decrease the total acid sites and strong acid sites of the Y zeolite from 291.5 and 44.6 μmol·g−1 to 244.2 and 32.1 μmol·g−1, respectively, which could obviously improve the dry gas and coke selectivity of the catalyst and thus enhance the nickel capacity for BM-Cat; on the other hand, under hydrothermal conditions, boron could react with NiO and form into NiB2O4, which could obviously raise the range of the reduction temperature for NiO from 350–600 °C to 650–800 °C and thus promote the nickel-passivation ability for BM-Cat. Therefore, evaluation results of heavy oil catalytic cracking indicated that, under the same nickel-contamination condition, in contrast to the compared catalyst (C-Cat), the dry gas yield, coke yield, and H2/CH4 of BM-Cat obviously decreased by 0.77 percentage points, 2.09 percentage points, and 13.53%, respectively, with light yield and total liquid yield increasing by 3.25 and 2.08 percentage points, respectively, which fully demonstrates the excellent anti-nickel contamination performance of BM-Cat.