bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTGF promotes cementogenesis and cementum repair via Cx43/β-catenin axis
Authors: wu Zuping , HE yuying , chen sirui , Zhu Li , Wang Jiahe , Zhang Demao , Xie Jing , Zou Shujuan , Zhou Chenchen 
Published: April 2022

Abstract
Background: Orthodontic tooth movement always induces cementum resorption inevitably, which is an urgent problem for orthodontists to confront. Human Periodontal ligament stem cells (hPDLSCs) possess multidirectional differentiation ability. Connective tissue growth factor (CTGF) is an important extracellular matrix proteins for bone homeostasis and cell differentiation. The purpose is to explore the role of CTGF in cementum repair and cementogenesis, and to elucidate its underlying mechanism.Methods: The cementum defect model was established by the gravity tooth movement, and the cementum repair effect of CTGF was observed by Micro CT, HE staining and immunohistochemical staining. RT-qPCR, Western bolt (WB), alizarin red and ALP activity experiments verified the mineralization ability of hPDLSCs stimulated by CTGF. In vivo and in vitro experiments, the expression of Cx43 in periodontal ligament cells was detected after CTGF stimulation by WB and immunofluorescence (IF) experiments. Subsequently, the mineralization ability of hPDLSCs were observed after the application of small interfering RNA Si-Cx43 and CTGF. Additionally, the co-intervention of small interfering RNA Si-CTGF and Cx43 agonist ARAT on hPDLSCs was applied to deepen the mechanism. Next, WB, IF experiments and co-immunoprecipitation were applied to confirm whether CTGF triggered Cx43/β-catenin axis to regulate cementoblast differentiation of hPDLSCs.Results: Local oral injection of CTGF to the cementum defects in vivo facilitated cementum repair. CTGF facilitated the cementogenesis of hPDLSCs in concentration-dependent manners. Cx43 acted as a CTGF downstream effector protein to regulate cementoblast differentiation. Si-Cx43 diluted CTGF-induced cementoblast differentiation. Cx43 agonists ATRA restored the low differentiation capacity induced by Si-CTGF. Further mechanistic studies showed that CTGF triggered the activation of β-catenin in a dose-dependent manner. Besides, colocalization analysis by IF and co-immunoprecipitation demonstrated that Cx43 interacted with β-catenin at the cell-cell connection. Si-Cx43 attenuated the enormous expression of β-catenin induced by CTGF. Cx43 agonists reversed the Si-CTGF-induced inhibition of β-catenin. IF demonstrated that the nuclear importation of β-catenin is related to the immense expression of Cx43 at cell-cell junctions. Conclusions: Taken together, these data demonstrated that CTGF promoted cementum repair and cementogenesis through activation of the Cx43/β-catenin signaling axis.
Educational needs in the management of patients with eosinophilic esophagitis: results of a US-based multispecialty case survey
Authors: Stacy Sylvie , Belcher Emily , Salinas Gregory 
Published: April 2022

Abstract
BackgroundGiven that the incidence of eosinophilic esophagitis (EoE) has been increasing, it is crucial that physicians are able to identify EoE, begin appropriate treatment, adjust treatment as needed, and work with patients to ensure adherence.AimsThe purpose of this study was to understand physician practice patterns and perceptions relating to EoE management.MethodsA patient case-based survey was developed to investigate physician practices related to the management of EoE. It was distributed to primary care physicians, allergists, gastroenterologists, and emergency physicians in January 2021.ResultsWhen respondents (n = 652) were presented a patient with newly diagnosed EoE who had trialed a proton pump inhibitor, only about half would begin combination pharmacotherapy and dietary therapy. Of those beginning pharmacotherapy, 75% would recommend a topical glucocorticoid and 68% would continue a PPI. There was no consensus regarding specific recommendations for dietary therapy. In refractory EoE, more allergists (39%) would begin a biologic agent than other physicians (14%). Though the majority of pediatricians (62%) would defer to a gastroenterologist specialist, fewer PCPs (43%) or allergists (9%) would do so. More allergists and gastroenterologists than other specialty types indicated that their EoE management is guided by a standard approach. The most significant barrier to optimal management was felt to be poor patient adherence, though 25% of physicians would not routinely assess adherence at follow-up.ConclusionsResults highlight current gaps in managing EoE, which can inform areas of focus for future educational activities, potentially leading to less practice variation and increased use of evidence-based decision-making.
Adsorption of Methylene Blue on Babassu Coconut (Orbignya speciosa) Mesocarp Commercial Biochar
Authors: Kasemodel Mariana Consiglio , Romão Erica Leonor , Papa Thiago Bueno Ruiz 
Published: April 2022

Abstract
Removal of organic dyes from wastewater by adsorption has advantages over conventional materials due to its low cost, abundance, adsorption capacity, and recycling. In this context, this study aims to evaluate the adsorption capacity of methylene blue in commercial babassu coconut mesocarp biochar. For this, biochar was characterized using physico-chemical parameters, proximate analysis, specific surface area (SBET) and surface functional groups. Batch-tests were carried out to identify the influence of biochar dose, initial dye concentration, granulometric fraction and time in the adsorptive process. The mixture was kept on a rotary shaker at room temperature, and the concentration was determined in a UV-VIS spectrophotometer. Results were analyzed using kinetic and isotherm models. The SBET of the commercial biochar was of 484.9 m² g− 1. The optimal conditions were using a biochar dose of 5 g L− 1, initial dye concentration inferior to 300 mg L− 1 and biochar granulometric fraction inferior to 0.15 mm. Elovich kinetic model (R2 > 0.8742) was most suitable to represent the MB adsorption onto babassu coconut mesocarp biochar. The equilibrium adsorption data were best described by the Langmuir model (R2 > 0.9897), with qm = 67.6 mg g− 1.
A novel route for the synthesis of 2-chloro-3-[trans-4-(4-chlorophenyl) cyclohexyl]-1,4-naphthoquinone and its process development studies
Authors: S SANJAY S 
Published: April 2022

Abstract
Present work reports a novel and commercially viable method for the synthesis of 2-chloro-3-[trans-4-(4-chlorophenyl) cyclohexyl]-1,4-naphthoquinone 1, a renowned intermediate of Atovaquone (an antimalarial drug). Majority of the prior arts disclose the synthesis of this intermediate from the expensive starting material 2-chloro-1,4-naphthoquinone 2, in relatively low yield. In this regard, it was considered worthwhile to synthesize 1 by a novel route using cheaper starting material 2,3-dichloro-1,4-naphtoquinone 5, in high yield and purity. In the present study, emphasis was given for selecting the reagents and solvents, optimizing the reaction conditions, recovery and reuse of solvents and silver salt. This optimized novel process is cost effective and generate less effluents.
Coasting along the effects of climate change: the challenges of adapting our anthropogenic shorescapes to new uncertain conditions
Authors: Brugnach Marcela , Hoek Ronald van den 
Published: April 2022

Abstract
Nature Based Solutions (NbS) are mainstreamed as an innovative and adequate approach to climate change. Combining natural dynamics and materials with technical knowledge, NbS are seen as a promising venue for coastal adaptation. However, little still is known about the role that the many uncertainties associated with such projects play in the effectiveness of these solutions, and about how to cope with these uncertainties, considering the impacts NbS may have for our society. Here, we investigate, if and how, managing uncertainties via the cascades of interrelated uncertainties conceptual framework improves the governance capacity for implementing NbS coastal management projects. To this end, we conduct an ex-post analysis of the uncertainties in two NbS study cases: Sand Engine and Safety Buffer Oyster Dam BwN projects in The Netherlands, critically analyzing through the conceptual framework, how uncertainties were addressed and proposing better fit supporting alternatives. Our results indicate major benefits for uncertainty management, supporting project development and implementation: generating more flexibility in managing under unknown conditions, being able to anticipate conflict, providing opportunities of creating new supporting relationships and alternative solutions.
Prognostic Biomarker DPY19L1 Reduces Survival in Glioma Patients
Authors: Lin Po-Chun , Chung Ming-Hsuan , Wang Peng-Wei , Huang Li‑Chun , Chen Ssu‑Han , Hueng Dueng-Yuan , Hung Kuang-Chen 
Published: April 2022

Abstract
Four homologous genes of C. elegans dpy-19 had been recognized in human. DPY19L1 is critical in neuronal migration of cerebral corticogenesis. However, there is no study investigated in the correlation between DPY19L1 and human gliomas. We performed analyses of Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA) which revealed overexpression of DPY19L1 in higher-grade gliomas. Moreover, Kaplan-Meier survival analysis of TCGA and CGGA datasets demonstrated that higher DPY19L1 level shortened survival outcome in glioma patients (P < 0.05 by log-rank test). Furthermore, the gene expression, protein level of DPY19L1 were higher in glioma cell lines than in normal brain control corroborated by quantitative RT‑PCR and Western blot. Immunohistochemical staining of human glioma samples showed enhancement of DPY19L1 expression in high-grade glioma than in low-grade glioma. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was studied to explore the protein-protein interaction of DPY19L1. In conclusion, elevation in DPY19L1 expression associates with higher WHO pathological grading and poor prognosis, and DPY19L1 might serve as a predictive biomarker of disease progression in gliomas.
Deficiency of murine UFM1-specific E3 ligase causes microcephaly and inflammation
Authors: Zhang Jie , Zhu Huabin , Liu Siyang , Quintero Michaela , Zhu Tianyi , Xu Renshi , Cai Yafei , Han Ye , Li Honglin 
Published: April 2022

Abstract
The UFM1 conjugation system is a Ubiquitin (Ub) -like modification system that is essential for animal development and normal physiology of multiple tissues and organs. It consists of UFM1, a Ub-like modifier, and the UFM1-specific enzymes (namely E1 enzyme UBA5, E2 enzyme UFC1 E2, and E3 ligases) that catalyze conjugation of UFM1 to its specific protein targets. Clinical studies have identified rare genetic variants in human UFM1, UBA5 and UFC1 genes that were linked to early-onset encephalopathy and defective brain development, strongly suggesting the critical role of the UFM1 system in the nervous system. Yet the phsyiologica function of this system in adult brain remains not defined. In this study, we investigated the role of UFM1 E3 ligase in adult mouse and found that both UFL1 and UFBP1 proteins, two components of UFM1 E3 ligase, are essential for survival of mature neurons in adult mouse. Neuron-specific deletion of either UFL1 or UFBP1 led to significant neuronal loss and elevation of inflammatory response. Interestingly, loss of one allele of UFBP1 genes caused occurance of seizure-like events. Our study has provided genetic evidence for the indispensable role of UFM1 E3 ligase in mature neurons and further demonstrated the importance of the UFM1 system in the nervous system.
The Effects of Different Endodontic Cavities on the Fracture Resistance of Endodontically Treated Mandibular First Molars- A Three-dimensional Finite Element Analysis
Authors: Wang Xiao , Wang Wei , Wang Dan , Wang Yirong , Qiu Xinyu , Cheng Xiaogang , Ni Longxing , Tian Yu 
Published: April 2022

Abstract
Objectives: The purpose of this study was to predict the fracture resistance of endodontically treated mandibular first molars (MFMs) with diverse minimally invasive endodontic access cavities using finite element models.Materials and Methods: Based on microcomputed tomographic data of an MFM, five three-dimensional finite element models representing a natural tooth (NT) and 4 endodontically treated MFMs were generated using finite element analysis software (HyperWork 14.0, Altair, USA). Treated MFM models were with a traditional endodontic cavity (TEC) and minimal invasive endodontic (MIE) cavities, including a computer-aided designed guided endodontic cavity (GEC), contracted endodontic cavity (CEC) and truss endodontic cavity (TREC). Three loading conditions were applied, simulating a maximum bite force of 600 N vertically and a normal masticatory force of 225 N vertically and laterally. The distributions of von Mises (VM) stress and peak VM stress were calculated.Results: The peak VM stresses of the NT model were the lowest under normal masticatory forces. In endodontically treated models, the distribution of VM stress in GEC model under all loads was the most similar to NT model. The peak VM stresses of the GEC and CEC models under different forces were lower than those of TREC and TEC models. The peak VM stresses of the GEC were lower than those of the CEC under normal masticatory loads but higher under maximum bite load. Under two vertical loads, the peak VM stresses of the TREC model were the highest, while under the lateral load, the peak VM stress of the TEC model was the highest. However, the VM stress in most part of the TEC model was higher than that in TREC model under all loads. Conclusions: Compared with TEC, GEC and CEC could better improve the fracture resistance of teeth. TREC may have a limited effect on fracture resistance enhancement when compared to GEC and CEC.Clinical Relevance: Our data demonstrated that compared with TEC and TREC, GEC and CEC access could better improve the fracture resistance of endodontically treated teeth, which may be an alternative balancing biomechanical properties and clinical convenience.
Comprehensive Analysis of Prognostic Value and Immune Infiltration of Src Family Kinases in Hepatocellular Carcinoma
Authors: Yao Dingjin , Deng Yiran , Zhang Si , Liang Limiao , Zhang Li , Weng Shuqiang , Chen She 
Published: April 2022

Abstract
Background: Src family kinases (SFKs) belong to the non-receptor protein tyrosine kinases family which are generally dysregulated in a variety of tumors. This study aims to thoroughly investigate the mutation status, expression level, prognostic value and relationship with immune infiltration of SFKs in hepatocellular carcinoma (HCC). Methods: TIMER2.0, UALCAN, cBioPortal, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, STRING, GeneMANIA and XIANTAO platform were utilized to analyze differential expression, genetic alteration, prognostic value and immune cell infiltration of SFKs in HCC patients. Furthermore, we used quantitative real-time PCR (qPCR) and western blot analysis to measure SFKs mRNA and protein expression in matching specimens of normal tissue versus HCC. We analyzed the biological effects of overexpressing FYN in Huh7 cells and subcutaneous xenograft tumor model. Results: The mRNA expression levels of LYN, SRC and SRM were elevated in HCC tissues, whereas FYN was reduced. Around 10% genetic alterations rate of SFKs was observed in HCC. The mRNA levels of BLK, BRK, FRK, FYN, LCK, LYN, SRC, SRM and YES were correlated with clinical cancer stage. Elevated FYN mRNA level in HCC was positively correlated with overall survival (OS), while SRC was negatively correlated with OS. The interaction network and functional enrichment analysis implied that SFKs were closely associated with the regulation of immune cells, cell adhesion molecules and signaling pathways involved in tumorigenesis and development. And all SFKs members in HCC were significantly relevant to at least half of the six imune-infiltrating cells, including B cells, macrophages, dendritic cells, neutrophils, CD4+ T cells and CD8+ T cells. Furthermore, we confirmed that the protein expression level of FYN was decreased in HCC patients and human hepatoma cell line. Overexpression of FYN suppressed Huh7 cell proliferation, migration, invasion, and tumorigenesis in xenografts nude mice.Conclusion: Dysregulated FYN and SRC expression in HCC is associated with poor prognosis and might be used as novel potential prognostic biomarkers in HCC patients.
Harm reduction implementation among HIV service organizations (HSOs) in the U.S. South: a policy context analysis and results from a survey of HSOs.
Authors: Stanton Megan , McCormick Katie , Ali Samira 
Published: April 2022

Abstract
Background. HIV service organizations are integral to serving communities disproportionately impacted by the HIV and opioid epidemics in the U.S. South. Addressing these intersecting epidemics requires implementation of evidence-based approaches, such as harm reduction. However, little is known about the extent to which Southern HIV service organizations implement harm reduction. This manuscript examines: 1) the implementation context of harm reduction in the South, 2) Southern HIV service organization implementation of harm reduction, and 3) the impact of different contexts within the South on HIV service organization implementation of harm reduction. Methods. To examine implementation context, authors analyzed nation-wide harm reduction policy and drug-related mortality data. To examine HIV service organization implementation of harm reduction, authors performed frequency distributions on survey data (n=207 organizations). Authors then constructed logistic regressions, using state mortality data and policy context as predictors, to determine what contextual factors predicted HIV service organization implementation of harm reduction.Results. Drug-related mortality data revealed an increased need for harm reduction, and harm reduction policy data revealed an increased political openness to harm reduction. Frequency distributions revealed that approximately half of the HIV service organizations surveyed reported that their organizations reflect a harm reduction orientation, and only 26% reported providing harm reduction services. Despite low utilization rates, HIV service organizations indicated a strong interest in harm reduction. Logistic regressions revealed that while increased mortality rates do not predict HIV service organization implementation of harm reduction, a harm reduction-friendly policy context does. Discussion. This study highlights how regions within high-income countries can face unique barriers to healthcare and therefore require a unique understanding of implementation context. Study findings indicate a rapidly changing implementation context where increased need meets increased political opportunity to implement harm reduction, however there is a lag in HIV service organization adoption of harm reduction. Financial resources, capacity building, and continued policy advocacy are required for increased HIV service organization adoption of harm reduction.
Integrated Optical Frequency Comb for 5G NR Xhauls
Authors: Lima Eduardo Saia , Borges Ramon Maia , Andriolli Nicola , Conforti Evandro , Contestabile Giampiero , S Arismar Cerqueira. 
Published: April 2022

Abstract
We experimentally demonstrate the use of optical frequency combs (OFC), generated by a photonic integrated circuit (PIC), in a flexible optical distribution network based on fiber-optics and free-space optics (FSO) links, aiming the fifth generation of mobile network (5G) Xhauls. The Indium Phosphide (InP) monolithically integrated OFC is based on cascaded optical modulators and is broadly tunable in terms of operating wavelength and frequency spacing. Particularly, our approach relies on applying the PIC in a centralized radio access network (C-RAN) architecture, with the purpose of optically generating two low-phase noise mm-waves signals for simultaneously enabling a 12.5-km of single-mode fiber (SMF) fronthaul and a 12.5-km SMF midhaul, followed by a 10-m long FSO fronthaul link. Moreover, the demonstrator contemplates two 10-m reach 5G wireless access networks operating in the 26 GHz band, i.e. over the frequency range 2 (FR2) from the 5G NR standard. The proposed integrated OFC-based 5G system performance is in accordance to the 3rd Generation Partnership Project (3GPP) Release 15 requirements, achieving a total wireless throughput of 900 Mbit/s.
The role of pornography in the sex life of young adults - a cross-sectional cohort study on female and male German medical students
Authors: Jahnen Matthias , Zeng Leopold , Kron Martina , Meissner Valentin H. , Korte Alexander , Schiele Stefan , Schulwitz Helga , Dinkel Andreas , Gschwend Jürgen E. , Herkommer Kathleen 
Published: April 2022

Abstract
Background: Due to easy online accessibility of pornography its consumption is popular among adolescents and young adults. Considering recently developed frameworks on the effects of sexual media, we assessed how increased consumption of pornography is associated with the experience of certain aspects of offline and online sexual activity in German medical students. Methods: Between April 2018 and March 2020 medical students from the Technical University of Munich in Germany were anonymously surveyed with regards to their sexual behavior, consumption of pornography, and use of social media. 468 students (female: n=293; male: n=175) were included in the current analysis. Data was analyzed using simple and multiple Poisson regression analysis.Results: Only 7.3% of female students but the majority of male students (79.1%) consumed pornography more than 4 times in the last 4 weeks. Female and male students who reported to be inspired by pornography (female: 52.0%, male: 74.6%) and who have enjoyed the experience of anal intercourse in their life (female: 17.1%, male: 32.2%) consumed pornography more frequently. Female students who have experienced a “threesome” (9.0%), have sent erotic pictures of themselves (33.5%), or use social media in their dating life (27.6%) consumed pornography more frequently. Male students who did not experience a sexual transmitted disease (82.9%) and did not cheat on their partner (68.0%) consumed pornography more frequently (results of multiple Poisson regression analysis; all p < 0.05).Conclusions: Many students consider pornography as inspiration for their sex life and frequent consumption of pornography seems to be associated with gender specific characteristics congruent with short-term sexual quality . The desire of adolescents and young adults for practical information about sexual intercourse should be addressed openly and a proper understanding of the sexuality shown in pornography should be taught.
How Does Random Spike Timing Code Anything?
Authors: Gilbert Mike 
Published: April 2022

Abstract
Nerve cells send signals to each other by discharging action potentials (spikes), the fast and brief depolarisation of cell membrane potential which propagates away from the cell body (soma). Traditionally, the two main candidates to code information in signals are spike frequency (firing rate) and spike timing. However, some cells – including Purkinje cells in the cerebellum – spike with unpredictably irregular timing, so that it is not obvious how it could be either, or indeed how it codes anything at all. Purkinje cells powerfully modulate firing of the output cells of the cerebellum. This paper argues that information is coded in the millisecond-to-millisecond probability of a Purkinje cell spike. Coded this way, firing of a single cell is meaningless, but the probability is synchronised at the level of functional groups of Purkinje cells – microzones – which form part of the cerebellar circuit. Around forty Purkinje cells converge on a cerebellum output cell. Because spike probability, but not timing, is synchronised among microzone-grouped Purkinje cells, the combined spike rate received by an output cell accurately and smoothly represents the group-coded probability. In this manner, irregular spike timing of single Purkinje cells is turned into analog modulation of output cell firing.