bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resonant Collisions Among Two-Dimensional Localized Waves in the Mel'nikov Equation
Authors: Xu Yinshen , Mihalache Dumitru , He Jingsong 
Published: August 2021

Abstract
We study the resonant collisions among different types of localized solitary waves in the Mel'nikov equation, which are described by exact solutions constructed using Hirota's direct method. The elastic collisions among different solitary waves can be transformed into resonant collisions when the phase shifts of these solitary waves tend to infinity . First, we study the resonant collision among a breather and a dark line soliton. We obtain two collision scenarios: (i) the breather is semi-localized in space and is not localized in time when it obliquely intersects with the dark line soliton, and (ii) the breather is semi-localized in time and is not localized in space when it parallelly intersects with the dark line soliton. The resonant collision of a lump and a dark line soliton, as the limit case of resonant collision of a breather and a dark line soliton, shows the fusing process of the lump into the dark line soliton. Then we investigate the resonant collision among a breather and two dark line solitons. In this evolution process we also obtain two dynamical behaviors: (iii) when the breather and the two dark line solitons obliquely intersect each other we get that the breather is completely localized in space and is not localized in time, and (iv) when the breather and the two dark line solitons are parallel to each other, we get that the breather is completely localized in time and is not localized in space. The resonant collision of a lump and two dark line solitons is obtained as the limit case of the resonant collision among a breather and two dark line solitons. In this special case the lump first detaches from a dark line soliton and then disappears into the other dark line soliton. Eventually, we also investigate the intriguing phenomenon that when a resonant collision among a breather and four dark line solitons occurs, we get the interesting situation that two of the four dark line solitons are degenerate and the corresponding solution displays the same shape as that of the resonant collision among a breather and two dark line solitons, except for the phase shifts of the solitons, which are not only dependent of the parameters controlling the waveforms of the solitons and the breather, but also dependent of some parameters irrelevant to the waveforms.
Fibroblast Growth Factor 21 Attenuates Salt-sensitive Hypertension-induced Nephropathy Through Anti-inflammation and Anti-oxidation Mechanism
Authors: Weng Hua-Chun , Lu Xin-Yu , Xu Yu-Peng , Wang Yi-Hong , Wang Dan , Feng Yi-Ling , Chi Zhang , Yan Xiao-Qing , Lu Chao-Sheng , Wang Hongwei 
Published: August 2021

Abstract
BackgroundPatients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy.MethodsChanges of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested.ResultsWe observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. ConclusionThese findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.
Evaluation of Cytotoxicity and Apoptotic behavior of Cerium Oxide/Zinc Oxide/ Graphene Oxide in HeLa and VERO cell Lines
Authors: J saranya , Sre BS , Arivanandan M , Bhuvaneswari K , Sherin S , Shivani K S , Saroja K K , SaradhaPreetha G 
Published: August 2021

Abstract
Using the ultrasonic approach, we produced a morphology involving cerium oxide/ Zinc oxide/graphene oxide (CeO2/ZnO/GO) nanocomposite-based system. The developed nanocomposite was examined using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM). The average crystallite size was found to be 11.44 nm, as determined by XRD. FTIR analysis was used to confirm the existence of functional groups. FESEM was used to verify the morphological properties of CeO2/ZnO/GO. The micromorphology of CeO2/ZnO/GO nanocomposite reveals a smoother sheet-like structure. In addition, using an antiproliferative assay test, the developed nanosystem was evaluated for its scavenging anti-cancer capability against HeLa cell lines at various doses and incubation intervals. In our investigation, the effective IC50 concentration was reported to be 62.5 µg/ml at 72 h. Further, the developed nanosystem was evaluated for its killing efficacy against normal cell line. To identify apoptosis-associated alterations of cell membranes throughout the apoptosis process, a dual acridine orange/ethidium bromide (AO/EB) fluorescent staining was done using CeO2/ZnO/GO nanocomposite at three specific concentrations. The quantitative analysis was carried out using flow cytometry (FACS study) to determine the cell cycle during which the greatest number of HeLa cells were destroyed. According to the results of the FACS investigation, maximum cell cycle has taken place in P2, P4.As a result, the newly designed CeO2/ZnO/GO hybrid has demonstrated improved anti-cancer efficacy against the HeLa cell line, making it a better therapeutic agent for cervical cancer detection.
Improving Smoking Cessation After Myocardial Infarction by Systematically Implementing Evidence-Based Treatment Methods: A Retrospective Observational Cohort Study
Authors: Leosdottir Margret , Wärjerstam Sanne , Michelsen Halldora Ögmundsdottir , Schlyter Mona , Hag Emma , Wallert John , Larsson Matz 
Published: August 2021

Abstract
Background: Evidence-based methods for aiding smoking cessation post-myocardial infarction are effective yet underused in clinical practice. We compared the odds of smoking cessation at 2-months post-myocardial infarction before versus after implementing a set of pre-specified routines optimizing evidence-based treatment methods for smoking cessation, initiated during admission. Methods: Structured routines for early smoking cessation counselling and treatment optimization were implemented at six cardiac rehabilitation centres in Sweden. The routines included cardiac rehabilitation nurses providing current smokers hospitalized for acute myocardial infarction with short consultation, written material, and optimal dosage of nicotine replacement therapy during admission, increasing early prescription of varenicline for eligible patients, and contacting the patients by telephone 3-5 days after discharge, after which usual care follow-up commenced. Centres were also encouraged to strive for continuity in nurse-patient care. Using logistic regression, we compared the odds for smoking cessation at 2-months post-discharge for currently smoking patients admitted (a) before (n=188, median age 60 years, 23% females) and (b) after (n=195, median age 60 years, 29% females) routine implementation. Secondary outcomes included adherence to implemented routines and the association of each routine with smoking cessation odds at 2-months.Results: In total, 159 (85%) and 179 (92%) of enrolled patients attended the 2-month follow-up, before and after implementation of the new routines. After implementation, a significantly larger proportion of patients (65% vs 54%) were abstinent from smoking at 2-months (OR 1.60 [1.04-2.48], p=0.034). Including only those counselled during admission (n=89), 74% (vs 54%) were abstinent at 2-months (OR 2.50 [1.42-4.41], p=0.002). After the new routine implementation patients were counselled more frequently during admission (50% vs 6%, p<0.001), prescribed varenicline at discharge or during follow-up (23% vs 7%, p<0.001), and contacted by telephone during the first week post-discharge (18% vs 2%, p<0.001), compared to before. Being prescribed varenicline before discharge or during follow-up had the strongest independent association with smoking abstinence at 2-months (adjusted OR 4.09 [1.68-10.00], p=0.002).Conclusions: Our results support that readily available methods for aiding smoking cessation can be implemented effectively in routine practice, with possible beneficial effects on smoking cessation for the high-risk group of smoking myocardial infarction patients.
The Global Burden and Attributable Risk Factors of Chronic Lymphocytic Leukemia in 204 Countries and Territories from 1990 to 2019: Analysis Based on the Global Burden of Disease Study 2019.
Authors: Yao Yiyi , Lin Xiangjie , Li Fenglin , Jin Jie , Wang Huafeng 
Published: August 2021

Abstract
Chronic lymphocytic leukemia (CLL) is the most prevalent subtype of leukemia in Western countries. Evaluation of the epidemiological characteristics of CLL is warranted, especially in the current context of global population aging. CLL data including incidence, mortality, and disability adjusted life-years (DALYs) were extracted and estimated annual percentage changes (EAPCs) were calculated from the 2019 Global Burden of Disease (GBD) study. Social-demographic index (SDI) was collected to investigate the impaction of social development degree on epidemiological trends and risk analysis. The global incidence of CLL has increased dramatically from 40,537 in 1990 to 103,467 in 2019. A high incidence has been achieved in males and elder people. Countries and territories with high SDI tended to have higher global burden than low-SDI region. Of the risk factors, high body mass index and smoking were the major contributors for CLL-related mortality and DALYs. In summary, the global CLL burden continues to rise over the past 30 years. Although most of the CLL incidence and death occurred in high-SDI regions, the CLL burden tends to grow rapidest in middle-SDI regions compared with high-/low-SDI regions. Therefore, it is necessary to pay special attention on taking further measures to alleviate the growing burden of CLL.
Hydroxychloroquine Attenuates Myocardial Ischemic and Post-ischemic Reperfusion Injury by Inhibiting the Toll-like Receptor 9 – Type I Interferon Pathway
Authors: Marsh Katherine M. , Rastogi Radhika , Zhang Aimee , Wu Di , Kron Irving L. , Yang Zequan 
Published: August 2021

Abstract
Background: Hydroxychloroquine (HCQ) is a toll-like receptor (TLR) 7 and 9 inhibitor that has been used clinically for its anti-inflammatory effects. We hypothesized that HCQ would attenuate myocardial ischemia/reperfusion (IR) injury by inhibiting the TLR9 – type I interferon (IFN-I) pathway. Methods: The left coronary artery of wild-type (WT) C57BL/6 and congenic TLR9-/- mice was occluded for 40 minutes to induce myocardial ischemia, with or without 60 minutes of subsequent reperfusion (40’/0’ or 40’/60’). Treatment with TLR9 inhibitors ODN-2088 or HCQ, or with TLR9 agonist ODN-1826 was administered either before ischemia or before reperfusion to determine effect on infarct size (IS). Myocardial IS as a percentage of risk region was measured by TTC-Blue staining. After 40’/0’, cardiac perfusate (CP) was collected from harvested hearts and used to treat either intact WT mice after 20 minutes of ischemia or isolated splenocytes. IFNa and IFNb levels were measured in plasma and splenocyte culture supernatant, and HMGB1 and cfDNA levels were measured in CP. Results: After 40’/60’ of IR, WT mice treated with HCQ or ODN-2088 had significantly reduced IS. Both 40’/0’ ischemic injury and 40’/60’ IR injury were similarly attenuated in TLR9-/- mice and HCQ-treated WT mice. HCQ did not further reduce IS in TLR9-/- mice. TLR9-/- and HCQ-treated WT mice had significantly lower IFNa and IFNb in CP after 40’/0’ ischemic injury and in plasma after 40’/60’ IR. 40’/0’ CP or ODN-1826 significantly increased IS in WT mice undergoing 20’/60’ IR. CP-treated WT splenocytes produced significantly higher IFNa and IFNb in culture supernatant at 2 hours. HCQ significantly reduced the production of IFNa and IFNb. Conclusions: The TLR9 – IFN-I-mediated inflammatory response is an important contributor to both ischemic and post-ischemic myocardial IR injury. HMGB1 and cfDNA released from ischemic myocardium activated the intra-myocardial TLR9 – IFN-I inflammatory pathway during ischemia and the extra-myocardial TLR9 – IFN-I inflammatory pathway during reperfusion. Hydroxychloroquine reduces production of IFN-I and attenuates myocardial IR injury, likely by inhibiting the TLR9 – IFN-I pathway.
Modeling the relevance of immune and metabolic cues in the macrophage/fibroblast interplay during fibrosis
Authors: Setten Elisa , Castagna Alessandra , Nava-Sedeno Josue , Weber Jonathan , Carriero Roberta , Reppas Andreas , Volk Valery , Schmitz Jessica , Gwinner Wilfried , Hatzikirou Haralampos , Feuerhake Friedrich , Locati Massimo 
Published: August 2021

Abstract
Fibrosis is a progressive biological process leading to organ dysfunction in different clinical settings. As fibroblasts and macrophages are known as key cellular players for fibrosis development, we adopted an in vitro model to define the functional effects of inflammation, hypoxia, and the adaptive immune context on their functional interplay with respect to fibrosis development. Transcriptomic analysis defined the impact of each parameter, acting alone or in combination, on functional properties of both cell types, exposed individually or in a cell-cell contact. These in vitro signatures were matched with transcriptomic profiles generated on laser-captured glomeruli and cortical tubulointerstitial area isolated from human transplanted kidneys with advanced stages of glomerulosclerosis and interstitial fibrosis/tubular atrophy, two clinically relevant conditions associated with organ failure in renal allografts. In vitro signatures were also used to instruct the development of a mathematical model predicting the relevance of each parameter in fibrosis development scenario, which indicated tolerance to inflammatory infiltrates under otherwise favorable conditions and defined an operative window in which hypoxia exerts a crucial role, supported by the degree of inflammation. Observed signatures and model-based predictions strongly suggested that irreversible fibrosis development is the result of specific combinations of metabolic and inflammatory cues, which drive distinct profibrotic paths in the glomeruli and the tubulointerstitial compartments. These findings, which found confirmation in tissue-based quantitative immune-phenotyping of transplanted kidney biopsies, indicate that the combination of in vitro and in silico modeling represents a powerful systems medicine approach to dissect fibrosis pathogenesis and develop coordinated targeted approaches.
Potential Key Markers for Predicting the Prognosis of Gastric Adenocarcinoma based on the Expression of Ferroptosis Related LncRNA
Authors: Yanqun Cai , Susu Wu , Yifan Jia , Xiao Pan , Caiqin Li 
Published: August 2021

Abstract
Background Gastric cancer is one of the most common malignant tumors, and it ranks third in global cancer-related mortality. At present, there is still no optimal treatment for gastric cancer, which makes it important to identify new therapeutic targets. This research aims to identify new targeted treatments for gastric adenocarcinoma by constructing a ferroptosis-related lncRNA prognostic feature model.MethodsThe gene expression profile and clinical data of gastric adenocarcinoma patients were downloaded from TCGA database. FerrDb database was used to determine the expression of iron death related genes. We used R software to clean the TCAG gastric adenocarcinoma gene expression cohort and screen iron death related differential genes and lncrna, and then carried out go and KEGG functional enrichment analysis of the related differential genes. The potential prognostic markers and immune infiltration characteristics were determined by constructing prognostic model and multivariate validation of lncRNA related to ferroptosis prognosis. Finally, the characteristics of immune infiltration were determined by immune correlation analysis.ResultsWe identified 26 ferroptosis-related lncRNA with independent prognostic value. Kaplan-Meier analysis identified high-risk lncRNA associated with poor prognosis of STAD. The risk scoring model constructed by AC115619.1, AC005165.1, LINC01614, AC002451.1 was better than traditional clinicopathological features. The 1, 3, and 5-year survival rates of STAD patients were predicted by the nomogram. GSEA reveals the oxidative respiration and tumor-related pathways in different risk groups. Immune analysis found significant differences in the expression of immune checkpoint-related genes TNFSF9, TNFSF4 and PDCD1LG2 between the two groups of patients. Meanwhile, there were significant differences in APC co stimulation, CCR and checkpoint between the two groups.ConclusionBased on the prognostic characteristics of ferroptosis-related lncRNA, we identified the potential ferroptosis-related lncRNA and immune infiltration characteristics in gastric adenocarcinoma, which will help provide new targeted treatments for gastric adenocarcinoma.
Dorsal Skin Microbial Assemblages in Free-ranging Hellbenders, Cryptobranchus Alleganiensis, Associated With Subspecies and Chronic Toe Lesions, but Not With Chytrid Fungal Infection.
Authors: Hardman Rebecca Hale , LeCleir Gary , Fitzpatrick Benjamin , Irwin Kelly J. , Sutton William B. , Neto Jeronimo G. da Silva , Freake Michael , Walker Donald M. , Miller Debra L. 
Published: August 2021

Abstract
BackgroundSkin microbiomes are important components of skin health and have been shown to contribute to immunity in amphibians, especially against the chytrid fungus, Batrachochytrium dendrobatidis (Bd). Hellbenders (Cryptobranchus alleganiensis) are large aquatic amphibians (Order Caudata) native to the eastern United States that have experienced population declines of both the Ozark and eastern subspecies, C. a. bishopi and C. a. alleganiensis, respectively. In addition, ulcerative non-healing toe lesions have become increasingly prevalent in C. a. bishopi, in Arkansas (AR) where populations are now reduced to a single river. To evaluate the potential impacts of both chronic toe lesions and Bd on hellbender health, we compared dorsal skin microbial assemblages based on 16S rRNA gene amplicons between a declining Ozark hellbender population in Arkansas (AR) presenting lesions and a reference, recruiting, lesion-free, population of eastern hellbenders in eastern Tennessee (ETN). We further evaluated effects of mass and life stage across both subspecies, as well as toe lesion severity and Bd infection status within AR, to better understand the associations between microbiomes and disease in a wild salamander.ResultsWe found skin of ETN hellbenders to have greater bacterial alpha diversity compared to AR, with this disparity decreasing as Hill number order increased. Conversely, within AR, animals with more severe lesions had decreased alpha diversity than those with mild lesions, which became more pronounced with increasing Hill number. Further, the average microbial assemblage structure differed between ETN and AR. Specifically, AR communities displayed increased beta diversity compared to those from ETN, which appeared to be linked to toe lesion severity. Neither size class (mass) nor Bd infection status had a significant effect on alpha or beta diversity. Taxonomic analysis revealed ETN to have greater OTU abundance of phylum Cyanobacteria 24.3%) compared to AR (5.9%); whereas AR had increased abundance of Proteobacteria (48.5%), Firmicutes (9.1%), and Synergistetes (1.5%), in comparison to ETN (31.5%, 2.6%, 0.2%, respectively).ConclusionsResults demonstrate that eastern hellbenders of ETN have richer and less dispersed dorsal skin bacterial assemblages compared to Ozark hellbenders of AR. Furthermore, we suggest that increased severity of toe lesions may be linked to systemic changes resulting in skin microbial dysbiosis, independent of Bd infection. Although lesions remain to have an unknown etiology, this study is another step towards understanding skin bacterial microbiomes in hellbenders, and their potential associations with chronic disease.
Novel Humanized Monoclonal Antibodies for Targeting Hypoxic Human Tumors via Two Distinct Extracellular Domains of Carbonic Anhydrase IX
Authors: Zatovicova Miriam , Kajanova Ivana , Barathova Monika , Takacova Martina , Labudova Martina , Csaderova Lucia , Jelenska Lenka , Svastova Eliska , Pastorekova Silvia , Harris Adrian L , Pastorek Jaromír 
Published: August 2021

Abstract
Background Hypoxia in the tumor microenvironment (TME) is often the main factor in the cancer progression. Moreover, low levels of oxygen in tumor tissue may signal that the first or second-line therapy will not be successful. This knowledge triggers the inevitable search for different kinds of treatment that will successfully cure aggressive tumors. Due to its exclusive expression on cancer cells, carbonic anhydrase IX belongs to the group of the most precise targets in hypoxic tumors. CA IX possesses several exceptional qualities that predetermine its crucial role in targeted therapy. Its expression on the cell membrane makes it an easily accessible target, while its absence in healthy corresponding tissues makes the treatment practically harmless. The presence of CA IX in solid tumors causes an acidic environment that may lead to the failure of standard therapy. Methods Parental mouse hybridomas (IV/18 and VII/20) were humanized to antibodies which were subsequently named CA9hu-1 and CA9hu-2. From each hybridoma we obtained 25 clones. Each clone was tested for ADCC and CDC activity, affinity, extracellular pH measurement, multicellular aggregation analysis and real-time monitoring of invasion with xCELLigence system. ResultsBoth CA9hu-1 and CA9hu-2 are IgG1 antibodies and they were both examined in vivo. Here we describe anti-CAIX antibodies that can reverse the failure of standard therapy as a result of an acidic environment by modulating the TME. CA9hu-1 is directed at the conformational epitope of the catalytic domain, while CA9hu-2 targets the sequential epitope of the proteo-glycan domain. They are both able to induce an immune response, have high affinity, as well as ADCC and CDC activity. While the first one internalizes after binding to the antigen, the second one is able to reduce metastases formation. More importantly, they have both proved the ability to block the acidification of the extracellular environment. ConclusionCA9hu-1 and CA9hu-2 are the very first humanized antibodies against CA IX that are likely to become suitable therapies for hypoxic tumors. These antibodies can be applied in the treatment therapy of primary tumors and suppression of metastases formation.