bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma
Authors: Yang Mengkai , Zhang Tao , Zhang Yangfeng , Ma Xiaojun , Han Jing , Zeng Ke , Jiang Yafei , Wang Zongyi , Wang Zhuoying , Xu Jing , Hua Yingqi , Cai Zhengdong , Sun Wei 
Published: May 2021

Abstract
Background
Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown.

Methods
We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS.

Results
Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo.

Conclusion
Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients.
IDSM ChemWebRDF: SPARQLing small-molecule datasets
Authors: Galgonek Jakub , Vondrášek Jiří 
Published: May 2021

AbstractThe Resource Description Framework (RDF), together with well-defined ontologies, significantly increases data interoperability and usability. The SPARQL query language was introduced to retrieve requested RDF data and to explore links between them. Among other useful features, SPARQL supports federated queries that combine multiple independent data source endpoints. This allows users to obtain insights that are not possible using only a single data source. Owing to all of these useful features, many biological and chemical databases present their data in RDF, and support SPARQL querying. In our project, we primary focused on PubChem, ChEMBL and ChEBI small-molecule datasets. These datasets are already being exported to RDF by their creators. However, none of them has an official and currently supported SPARQL endpoint. This omission makes it difficult to construct complex or federated queries that could access all of the datasets, thus underutilising the main advantage of the availability of RDF data. Our goal is to address this gap by integrating the datasets into one database called the Integrated Database of Small Molecules (IDSM) that will be accessible through a SPARQL endpoint. Beyond that, we will also focus on increasing mutual interoperability of the datasets. To realise the endpoint, we decided to implement an in-house developed SPARQL engine based on the PostgreSQL relational database for data storage. In our approach, data are stored in the traditional relational form, and the SPARQL engine translates incoming SPARQL queries into equivalent SQL queries. An important feature of the engine is that it optimises the resulting SQL queries. Together with optimisations performed by PostgreSQL, this allows efficient evaluations of SPARQL queries. The endpoint provides not only querying in the dataset, but also the compound substructure and similarity search supported by our Sachem project. Although the endpoint is accessible from an internet browser, it is mainly intended to be used for programmatic access by other services, for example as a part of federated queries. For regular users, we offer a rich web application called ChemWebRDF using the endpoint. The application is publicly available at https://idsm.elixir-czech.cz/chemweb/.
The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation
Authors: Zhou Jing , Zhang Ning , Zhang Wei , Lu Caiju , Xu Fei 
Published: May 2021

AbstractBackgroundAsthma is a heterogeneous chronic inflammatory disease of the airway, involving reversible airflow limitation and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is limited understanding of the signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to investigate if the Yes-associated protein (YAP)/hypoxia inducible factor-1α (HIF-1α)/microRNA-182 (miR-182)/early growth response 2 (EGR2) axis is involved in mediating Th17 cell differentiation and disease severity in asthma.MethodsThe study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin-induced murine asthma models, and mouse naive CD4+T cells. The subpopulation of Th17 cells was examined by flow cytometry. The levels of interleukin-17A were determined by enzyme linked immunosorbent assay. Chromatin immunoprecipitation-quantitative polymerase chain reaction assays and dual-luciferase reporter gene assays were performed to examine interactions between HIF-1α and miR-182, and between miR-182 and EGR2.ResultsYAP, HIF-1α, and miR-182 were upregulated but EGR2 was downregulated in human and mouse peripheral blood mononuclear cells from the asthma group. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo overexpression of EGR2 countered the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction.ConclusionThese results indicate that activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, thus suggesting a potential therapeutic target for asthma.
Non-frontal facial expression recognition based on salient facial patches
Authors: Jiang Bin , Zhang Qiuwen , Li Zuhe , Wu Qinggang , Zhang Huanlong 
Published: May 2021

AbstractMethods using salient facial patches (SFPs) play a significant role in research on facial expression recognition. However, most SFP methods use only frontal face images or videos for recognition, and they do not consider head position variations. We contend that SFP can be an effective approach for recognizing facial expressions under different head rotations. Accordingly, we propose an algorithm, called profile salient facial patches (PSFP), to achieve this objective. First, to detect facial landmarks and estimate head poses from profile face images, a tree-structured part model is used for pose-free landmark localization. Second, to obtain the salient facial patches from profile face images, the facial patches are selected using the detected facial landmarks while avoiding their overlap or the transcending of the actual face range. To analyze the PSFP recognition performance, three classical approaches for local feature extraction, specifically the histogram of oriented gradients (HOG), local binary pattern, and Gabor, were applied to extract profile facial expression features. Experimental results on the Radboud Faces Database show that PSFP with HOG features can achieve higher accuracies under most head rotations.
Determinants of adherence to COVID-19 measures among the Belgian population: an application of the protection motivation theory
Authors: van Loenhout Joris Adriaan Frank , Vanderplanken Kirsten , Scheen Bénédicte , Van den Broucke Stephan , Aujoulat Isabelle 
Published: May 2021

Abstract
Background
Since the start of the COVID-19 outbreak, the Belgian government has implemented various infection prevention and control measures. This study assessed the extent to which the general population in Belgium adhered to these measures, and which determinants were associated with adherence.

Methods
We undertook an internet survey among a sample of the Belgian population, representative for sex, age, socio-economic status and province. The questionnaire included various demographic, socio-economic and health-related questions, and also drew upon the Protection Motivation Theory as a theoretical framework to measure levels of perceived severity, vulnerability, perceived usefulness of the measures (response efficacy), perceived personal capacity to adhere (self-efficacy), and past and future adherence. Data were collected in Dutch and French, the main languages of Belgium.

Results
Our study was carried out in September 2020, and the number of respondents was 2008. On average, respondents provided high scores for each of the measures in place in September in terms of response efficacy (range of 3.54–4.32 on 1 to 5 Likert-scale), self-efficacy (range of 3.00–4.00), past adherence (4.00–4.68) and future adherence (3.99–4.61). The measure that overall received the highest scores was wearing a face mask in public spaces, while ‘the social bubble of 5’ generally received the lowest scores. There was a statistically significant relationship between response efficacy and self-efficacy on the one hand and (past and future) adherence on the other hand, in a multivariate model corrected for confounders. Vulnerability and severity did not show statistical significance.

Conclusion
Risk communication regarding COVID-19 should place a stronger emphasis on helping people understand why implemented measures are useful and how they can be put into practice, more than on increasing fear appeals.
Housing, opportunities, motivation and engagement (HOME) for homeless youth at-risk for opioid use disorder: study protocol for a randomized controlled trial
Authors: Slesnick Natasha , Chavez Laura , Bunger Alicia , Famelia Ruri , Ford Jodi , Feng Xin , Higgins Sarah , Holowacz Eugene , Jaderlund Soren , Luthy Ellison , Mallory Allen , Martin Jared , Walsh Laura , Yilmazer Tansel , Kelleher Kelly 
Published: May 2021

AbstractBackgroundHomeless youth experience high rates of substance use disorders, exposures to violence, mental and physical health conditions, and mortality. They have been particularly affected by the opioid crisis. However, no study to date has used a randomized controlled design to test preventive interventions of opioid and other drug use among this vulnerable population. Resolution of youth homelessness through housing and supportive services including prevention services, often referred to as “Housing First,” has great potential to reduce the likelihood for the development of an opioid use disorder as well as other problem behaviors associated with living on the streets. Housing First has been tested through randomized trials among homeless adults with mental health and substance use disorders, but has not been empirically tested for opioid prevention among homeless youth.MethodsHomeless youth will be recruited from a drop-in shelter site frequented by disconnected youth; they will be screened for eligibility, including current homelessness, age 18–24 years, and not currently meeting criteria for opioid use disorder (OUD). In a controlled trial, 240 youth will then be randomized to one of two conditions, (1) housing + opioid and related risk prevention services, or (2) opioid and related risk prevention services alone. This project utilizes existing efficacious models of prevention to address opioid-related risks, including motivational interviewing, strengths-based outreach and advocacy, and an HIV risk preventive intervention. Follow-up will be conducted at 3, 6, 9 and 12-months post-baseline. The economic cost of each intervention will be determined to support implementation decisions with other providers and their funders.DiscussionThis study will provide essential information for researchers and providers on the efficacy of housing + opioid and related risk prevention services in an RCT for effects on opioid use and mechanisms underlying change. Because youth experiencing homelessness are at increased risk for a variety of adverse outcomes, the proposed intervention may produce substantial health care benefits to the youths and society at large.Trial registrationClinicalTrials.gov, NCT04135703, Registered October 13, 2019,https://clinicaltrials.gov/ct2/show/NCT04135703?term=NCT04135703&draw=2&rank=1#contacts
Patient outcomes and experience of a task-shared screening and brief intervention service for problem substance use in South African emergency centres: a mixed methods study
Authors: van der Westhuizen Claire , Malan Megan , Naledi Tracey , Roelofse Marinda , Myers Bronwyn , Stein Dan J. , Lahri Sa’ad , Sorsdahl Katherine 
Published: May 2021

Abstract
Background
Screening, brief intervention and referral to treatment (SBIRT) programmes have resulted in generally positive outcomes in healthcare settings, particularly for problem alcohol use, yet implementation is hampered by barriers such as concerns regarding the burden on healthcare professionals. In low-resourced settings, task-sharing approaches can reduce this burden by using non-professional healthcare workers, yet data are scarce regarding the outcomes and acceptability to patients within a SBIRT service. This study aims to evaluate patient-reported outcomes, patient acceptability, perceived benefits and recommendations for improving a task-shared SBIRT service in South African emergency centres (ECs).

Methods
This mixed methods study incorporates quantitative substance use screening and patient satisfaction data collected routinely within the service at three hospitals, and qualitative semi-structured interviews with 18 EC patient beneficiaries of the programme exploring acceptability and perceived benefits of the programme, as well as recommendations to improve the service. Approximately three months after the acute EC visit, a sub-sample of patients were followed up telephonically to assess patient-reported satisfaction and substance use outcomes.

Results
Of the 4847 patients eligible for the brief intervention, 3707 patients (76%) used alcohol as their primary substance and 794 (16%) used cannabis. At follow-up (n = 273), significant reductions in substance use frequency and severity were noted and over 95% of patients were satisfied with the service. In the semi-structured interviews, participants identified the non-judgemental caring approach of the counsellors, and the screening and psychoeducation components of the intervention as being the most valuable, motivating them to decrease substance use and make other positive lifestyle changes. Study participants made recommendations to include group sessions, market the programme in communities and extend the programme’s reach to include a broader age group and a variety of settings.

Conclusions
This task-shared SBIRT service was found to be acceptable to patients, who reported several benefits of a single SBIRT contact session delivered during an acute EC visit. These findings add to the SBIRT literature by highlighting the role of non-professional healthcare workers in delivering a low-intensity SBIRT service feasible to implement in low-resourced settings.
Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease
Authors: Cherry Jonathan D. , Esnault Camille D. , Baucom Zachary H. , Tripodis Yorghos , Huber Bertrand R. , Alvarez Victor E. , Stein Thor D. , Dickson Dennis W. , McKee Ann C. 
Published: May 2021

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.
Fertilizing behavior of extract of organomineral-activated biochar: low-dose foliar application for promoting lettuce growth
Authors: Kumar Abhay , Joseph Stephen , Graber Ellen R. , Taherymoosavi Sara , Mitchell David R. G. , Munroe Paul , Tsechansky Ludmila , Lerdahl Ove , Aker Walter , Sæbø Mona 
Published: May 2021

Abstract
Background
Fostering plant growth and improving agricultural yields by adding “macro”-sized biochar to soil has been extensively explored. However, the impact and mechanism of action of aqueous extracts of biochar applied as foliar fertilizer on plant growth and physiology is poorly understood, and was the objective of this study. Extracts were produced from biochars derived from pine wood:clay:sand (PCS-BC; 70:15:15) and wheat straw:bird manure (WB-BC; 50:50) and tested at two dilutions each. The plant influence of the biochar extracts and dilutions were compared with chemical fertilizer made up to the same minor trace element compositions as the applied extracts and a control treatment consisting of only deionized water.

Results
The WB-BC extract was more alkaline than the PCS-BC extract and exhibited higher electrical conductivity values. Similar to the biochars from which they were derived, the WB-BC extract had higher concentrations of dissolved mineral elements and organic matter than the PCS-BC extract. Despite major differences in chemical composition between the PCS-BC and WB-BC extracts, there was virtually no difference in plant performance between them at any chosen dilution. Foliar application of PCS25, WB50, and WB100 led to a significant increase in the plant fresh biomass in comparison to their corresponding chemical fertilizer and to deionized water. Plant growth parameters including number of leaves and chlorophyll contents in plants treated with biochar extract foliar sprays were significantly higher than in all the other treatments. Electron microscopy and spectroscopy studies showed the deposition of macro- and nanoscale organomineral particles and agglomerates on leaf surfaces of the examined PCS25-treated plant. Detailed study suggests that carbon nanomaterials and TiO2 or Si-rich nanoscale organomineral complexes or aluminosilicate compounds from biochar extract were main contributors to increased plant growth and improved plant performance.

Conclusion
These results suggest that biochar extracts have the potential to be used as nanofertilizer foliar sprays for enhancing plant growth and yield.
Paludification reduces black spruce growth rate but does not alter tree water use efficiency in Canadian boreal forested peatlands
Authors: Beaulne Joannie , Boucher Étienne , Garneau Michelle , Magnan Gabriel 
Published: May 2021

Abstract
Background
Black spruce (Picea mariana (Mill.) BSP)-forested peatlands are widespread ecosystems in boreal North America in which peat accumulation, known as the paludification process, has been shown to induce forest growth decline. The continuously evolving environmental conditions (e.g., water table rise, increasing peat thickness) in paludified forests may require tree growth mechanism adjustments over time. In this study, we investigate tree ecophysiological mechanisms along a paludification gradient in a boreal forested peatland of eastern Canada by combining peat-based and tree-ring analyses. Carbon and oxygen stable isotopes in tree rings are used to document changes in carbon assimilation rates, stomatal conductance, and water use efficiency. In addition, paleohydrological analyses are performed to evaluate the dynamical ecophysiological adjustments of black spruce trees to site-specific water table variations.

Results
Increasing peat accumulation considerably impacts forest growth, but no significant differences in tree water use efficiency (iWUE) are found between the study sites. Tree-ring isotopic analysis indicates no iWUE decrease over the last 100 years, but rather an important increase at each site up to the 1980s, before iWUE stabilized. Surprisingly, inferred basal area increments do not reflect such trends. Therefore, iWUE variations do not reflect tree ecophysiological adjustments required by changes in growing conditions. Local water table variations induce no changes in ecophysiological mechanisms, but a synchronous shift in iWUE is observed at all sites in the mid-1980s.

Conclusions
Our study shows that paludification induces black spruce growth decline without altering tree water use efficiency in boreal forested peatlands. These findings highlight that failing to account for paludification-related carbon use and allocation could result in the overestimation of aboveground biomass production in paludified sites. Further research on carbon allocation strategies is of utmost importance to understand the carbon sink capacity of these widespread ecosystems in the context of climate change, and to make appropriate forest management decisions in the boreal biome.