bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population genomics reveal rapid genetic differentiation in a recently invasive population of Rattus norvegicus
Authors: Chen Yi , Zhao Lei , Teng Huajing , Shi Chengmin , Liu Quansheng , Zhang Jianxu , Zhang Yaohua 
Published: January 2021

Abstract
Background
Invasive species bring a serious effect on local biodiversity, ecosystems, and even human health and safety. Although the genetic signatures of historical range expansions have been explored in an array of species, the genetic consequences of contemporary range expansions have received little attention, especially in mammal species. In this study, we used whole-genome sequencing to explore the rapid genetic change and introduction history of a newly invasive brown rat (Rattus norvegicus) population which invaded Xinjiang Province, China in the late 1970s.

Results
Bayesian clustering analysis, principal components analysis, and phylogenetic analysis all showed clear genetic differentiation between newly introduced and native rat populations. Reduced genetic diversity and high linkage disequilibrium suggested a severe population bottleneck in this colonization event. Results of TreeMix analyses revealed that the introduced rats were derived from an adjacent population in geographic region (Northwest China). Demographic analysis indicated that a severe bottleneck occurred in XJ population after the split off from the source population, and the divergence of XJ population might have started before the invasion of XJ. Moreover, we detected 42 protein-coding genes with allele frequency shifts throughout the genome for XJ rats and they were mainly associated with lipid metabolism and immunity, which could be seen as a prelude to future selection analyses in the novel environment of XJ.

Conclusions
This study presents the first genomic evidence on genetic differentiation which developed rapidly, and deepens the understanding of invasion history and evolutionary processes of this newly introduced rat population. This would add to our understanding of how invasive species become established and aid strategies aimed at the management of this notorious pest that have spread around the world with humans.
Identification and screening of host proteins interacting with ORFV-ORF047 protein
Authors: Chen Guohua , He Xiaobing , Jia Huaijie , Fang Yongxiang , Wang Xiaoxia , Lou Zhongzi , Yang Fan , Li Weike , Jing Zhizhong 
Published: January 2021

Abstract
Background
Orf virus (ORFV) is a member of the genus Parapoxvirus and family Poxviridae. The virus has a worldwide distribution and infects sheep, goats, humans, and wild animals. However, due to the complex structure of the poxvirus, the underlying mechanism of the entry and infection by ORFV remains largely unknown. ORFV ORF047 encodes a protein named L1R. Poxviral L1R serves as the receptor-binding protein and blocks virus binding and entry independently of glycosaminoglycans (GAGs). The study aimed to identify the host interaction partners of ORFV ORF047.

Methods
Yeast two-hybrid cDNA library of sheep testicular cells was applied to screen the host targets with ORF047 as the bait. ORF047 was cloned into a pBT3-N vector and expressed in the NMY51 yeast strain. Then, the expression of bait proteins was validated by Western blot analysis.

Results
Sheep SERP1and PABPC4 were identified as host target proteins of ORFV ORF047, and a Co-IP assay further verified their interaction.

Conclusions
New host cell proteins SERP1and PABPC4 were found to interact with ORFV ORF047 and might involve viral mRNA translation and replication.
Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers
Authors: Tumbo Anneth-Mwasi , Schindler Tobias , Dangy Jean-Pierre , Orlova-Fink Nina , Bieri Jose Raso , Mpina Maximillian , Milando Florence A. , Juma Omar , Hamad Ali , Nyakarungu Elizabeth , Chemba Mwajuma , Mtoro Ali , Ramadhan Kamaka , Olotu Ally , Makweba Damas , Mgaya Stephen , Stuart Kenneth , Perreau Matthieu , Stapleton Jack T. , Jongo Said , Hoffman Stephen L. , Tanner Marcel , Abdulla Salim , Daubenberger Claudia 
Published: January 2021

Abstract
Background
Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI).

Methods
HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI.

Results
The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5′ UTR and E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI.

Conclusions
HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.
Neuro-Muscular Dentistry: the “diamond” concept of electro-stimulation potential for stomato-gnathic and oro-dental conditions
Authors: Sandoval-Munoz Catalina P. , Haidar Ziyad S. 
Published: January 2021

AbstractOro-Pharyngeal Dysphagia - or simply dysphagia - is the difficulty (persistent) in swallowing/passing food and/or liquid from the mouth to the pharynx into the esophagus and finally the stomach; a deglutition disorder (a symptom, by definition, often due to neuro-degenerative/−muscular, drug-induced or localized structural pathologies such as head and neck tumors, lesions and associated surgical and/or radiation injuries) linked to severe consequences on Quality of Life (QoL), including malnutrition, dehydration, and even sudden death. Likewise, Temporo-Mandibular Jaw and Joint disorder(s) – or simply TMD – is a multifactorial etiological condition, regularly encountered in the dental office. Whether due to malocclusion, bruxism, stress and/or trauma, TMD destabilizes the whole cranio-mandibular system structurally and functionally, via affecting mastication, teeth, supporting structures, comfort and aesthetics, and thus, QoL, again. While several treatment regimens do exist for such conditions, some of which have been standardized for use over the years, most continue to lack proper evidence-based literature support. Hence, (1) caution is to be exercised; and (2) the need for alternative therapeutic strategies is amplified, subsequently, the door for innovation is wide open. Indeed, neuromuscular electrical stimulation or “NMES”, is perhaps a fine example. Herein, we present the interested oro-dental health care provider with an up-dated revision of this therapeutic modality, its potential benefits, risks and concerns, to best handle the dysphagic patient: an intra-disciplinary approach or strategy bridging contemporary dentistry with speech and language therapy; a rather obscure and un-discovered yet critical allied health profession. A pre-clinical and clinical prospectus on employing inventive NMES-based regimens and devices to manage TMD is also highlighted.
Prediction of hypericin content in Hypericum perforatum L. in different ecological habitat using artificial neural networks
Authors: Saffariha Maryam , Jahani Ali , Jahani Reza , Latif Sajid 
Published: January 2021

Abstract
Background
Hypericum is an important genus in the family Hypericaceae, which includes 484 species. This genus has been grown in temperate regions and used for treating wounds, eczema and burns. The aim of this study was to predict the content of hypericin in Hypericum perforatum in varied ecological and phenological conditions of habitat using artificial neural network techniques [MLP (Multi-Layer Perceptron), RBF (Radial Basis Function) and SVM (Support Vector Machine)].

Results
According to the results, the MLP model (R2 = 0.87) had an advantage over RBF (R2 = 0.8) and SVM (R2 = 0.54) models and it was relatively accurate in predicting hypericin content in H. perforatum based on the ecological conditions of site including soil types, its characteristics and plant phenological stages of habitat. The results of sensitivity analysis revealed that phenological stages, hill aspects, total nitrogen, altitude and organic carbon are the most influential factors that have an integral effect on the content of hypericin.

Conclusions
The designed graphical user interface will help pharmacognosist, manufacturers and producers of medicinal plants and so on to run the MLP model on new data to easily discover the content of hypericin in H. perforatum by entering ecological conditions of site, soil characteristics and plant phenological stages.
Opioid use, regulation, and harms in Brazil: a comprehensive narrative overview of available data and indicators
Authors: Maia Lucas O. , Daldegan-Bueno Dimitri , Fischer Benedikt 
Published: January 2021

Abstract
Background
Global opioid consumption increased multifold post-2000, disproportionately in high-income countries, with severe mortality/morbidity consequences. Latin America features comparatively low opioid availability; Brazil, the region’s most populous country, makes an interesting case study concerning opioid use/harms. In this comprehensive overview, we aimed to identify and summarize medical and non-medical data and indicators of opioid availability and use, regulation/control, and harm outcomes in Brazil since 2000.

Methods
We searched multiple scientific databases to identify relevant publications and conducted additional ‘grey’ literature searches to identify other pertinent information.

Results
Despite some essential indicators, opioid-related data are limited for Brazil. Data indicate that population-level availability of prescription opioids represents only a small fraction of use in comparison to high-income countries. However, within Latin America, Brazil ranks mid-level for opioid consumption, indicating relatively moderate consumption compared to neighboring jurisdictions. Brazil has implemented restrictive regulations to opioid prescribing and is considered ‘highly restricted’ for opioid access. Codeine remains the major opioid analgesic utilized, but stronger opioids such as oxycodone are becoming more common. Professional knowledge regarding medical opioid use and effects appears limited. National surveys indicate increases in non-medical use of prescription opioids, albeit lower than observed in North America, while illicit opioids (e.g., heroin) are highly uncommon.

Conclusions
Overall population-level opioid availability and corresponding levels of opioid-related harms in Brazil remain substantially lower than rates reported for North America. However, the available surveillance and analytical data on opioid use, policy/practice, and harms in Brazil are limited and insufficient. Since existing and acute (e.g., pain-related) needs for improved opioid utilization and practice appear to be substantiated, improved indicators for and understanding of opioid use, practice, and harms in Brazil are required.
Effect of a culturally safe student placement on students' understanding of, and confidence with, providing culturally safe podiatry care
Authors: West Matthew , Sadler Sean , Hawke Fiona , Munteanu Shannon E. , Chuter Vivienne 
Published: January 2021

AbstractBackgroundFor university‐based podiatry education there are little data available documenting the delivery method and impact of Aboriginal and Torres Strait Islander health curricula or the use of, and outcomes from, immersive clinical placements generally or specific to podiatry practice. Therefore, the primary aim of this study was to evaluate the effect of undertaking clinical placement in a culturally safe podiatry service for Aboriginal and Torres Strait Islander Peoples on podiatry students' understanding of, and confidence with, providing culturally safe podiatry care.MethodsFinal year University of Newcastle undergraduate podiatry students attending a culturally safe Aboriginal and Torres Strait Islander student clinic at a local hospital were purposively recruited to participate. Students completed a custom‐made and pilot‐tested cultural awareness and capability survey before and after placement. Survey domains were determined from a principle component analysis. The Wilcoxon Signed Rank test was used to compare pre‐placement scores on each domain of the survey to the post‐placements scores. Effect sizes were calculated and interpreted as small (0.1–0.29), medium (0.3–0.49), and large (≥0.5).ResultsThis study recruited 58 final year University of Newcastle podiatry students to complete baseline and follow‐up surveys. For survey domain 1 (level of understanding of power relationships), domain 2 (level of understanding of the interrelationship between culture and self‐perceived health), domain 3 (level of understanding of the importance of culture in clinical practice and access to health care), and domain 4 (level of confidence with providing culturally safe care) a statistically significant (p < 0.05) increase in scores was recorded post‐placement. The effect sizes were medium to large.ConclusionThis study demonstrated that an immersive student placement at a culturally safe podiatry clinic significantly improved students' understanding of, and confidence with, providing culturally appropriate care to Aboriginal and Torres Strait Islander Peoples. This study provides foundation evidence of the role that such placements have on developing students' cultural capability in a tertiary health care setting, and will help inform future curricula development at both educational institutions and health services, as well as form the basis for ongoing research.
Chinese herbal formula Xuefu Zhuyu for primary dysmenorrhea patients (CheruPDYS): a study protocol for a randomized placebo-controlled trial
Authors: Li Geng , Zhang Zhe , Zhou Li , Liao Shaojun , Sun Jing , Liu Yinghua , Wang Xin , Wen Zehuai 
Published: January 2021

Abstract
Background
Epidemiological studies have shown that young women often suffer from primary dysmenorrhea (PD) which is a common cause that affects their routine work and quality of life. Chinese herbal medicine has been widely used for PD in China. A systematic review found that Xuefu Zhuyu (XFZY) has a promising effect on PD management, yet there is a dearth of high-quality evidence in support of this claim. We want to conduct a randomized controlled trial to evaluate the efficacy and safety of XFZY for PD patients.

Methods
This is a protocol for a multicenter, randomized, placebo-controlled trial. A total of 248 participants with PD will be recruited at 6 centers and randomized into two groups—a herbal treatment group and a placebo group. The participants will receive either XFZY or placebo, three times per day, for 3 menstrual cycles, with a 12-week follow-up. The primary outcome will be the mean change in pain intensity as measured by VAS, while the change in menstrual pain duration, the change in peak pain intensity as measured by VAS, the Cox Menstrual Symptom Scale (CMSS), quality of life EQ-5D-5L, cumulative painkiller consumption, and health economics will be included as secondary outcomes. Adverse events will also be reported.

Discussion
This protocol describes a multicenter, double-blind, randomized, placebo-controlled trial that investigates the efficacy and safety of XFZY for primary dysmenorrhea. Validated evaluation tools will assess dysmenorrhea severity. We believe that this research will provide important evidence regarding the use of XFZY to treat dysmenorrhea.

Trial registration
Chinese Clinical Trial Registry ChiCTR1900026819. Registered on 23 October 2019
Concentration of survivin in children with oligo- and polyarticular juvenile idiopathic arthritis (JIA): diagnostic and prognostic value—a single-center study
Authors: Lipinska Joanna , Kaszkowiak Marcin , Malachowska Beata , Swidrowska-Jaros Joanna , Smolewska Elzbieta 
Published: January 2021

Abstract
Aim
The goal of the study was to assess the diagnostic and prognostic utility of survivin in patients with juvenile idiopathic arthritis (JIA).

Methods
Seventy children with JIA—59 newly diagnosed and 11 biologically treated (46 girls and 17 boys) aged 1.5–18 years and 29 healthy children as a control group, appropriately matched in terms of sex and age, were included in the study. The disease activity was established on the basis of the JADAS-27 criteria. The concentration of survivin was assessed by an ELISA test in serum and also 18 matched synovial fluid samples collected from patients with JIA.

Results
Children with JIA were divided according to the subtype of the JIA. In 65.7% of patients, oligoarthritis was diagnosed. The largest group comprised children of low disease activity (62.9%) according to JADAS-27. The serum concentration of survivin was significantly higher in children with JIA compared to the controls (p < 0.001). The concentration of survivin was higher among patients positive for anti-cyclic citrullinated peptide autoantibodies (ACPA) (p = 0.001). In all synovial fluid samples, the concentration of survivin was higher than in matched serum (p = 0.003). Serum survivin concentration was not significantly associated with radiological damage status or active synovitis assessed by joint ultrasonography. Survivin level was not significantly associated with disease duration time or treatment with TNF-α inhibitors in DMARD’s non-responders.

Conclusions
Survivin should be considered as a biomarker of joint inflammation helpful in the diagnosis of oligo- and polyarticular JIA and probably not dependent on treatment with TNF-α inhibitors.
Are meat options preferred to comparable vegetarian options? An experimental study
Authors: Pechey Rachel , Hollands Gareth J. , Marteau Theresa M. 
Published: January 2021

Abstract
Objective
Reducing meat consumption would have substantial benefits both in terms of health and environmental impact, but meat options may be more attractive to customers than meat-free options. This study tested this by presenting UK adults (n = 540) with a series of pictures showing two meal options and asking them to select which they would prefer to eat right now. They completed this task for every possible pair from a pool of six comparator meat-based options and six target options (66 pairs). Participants all saw identical comparator options, and were randomised to see the same pictures of target options but with descriptions that suggested they were either meat-based or vegetarian.

Results
Selections were used to rank the options for each individual from 1 (most-selected) to 12 (least-selected). Vegetarian target options were ranked worse [by 1.23 places (95% CI: 1.02, 1.44)] than meat target options. Higher self-reported consumption of meat predicted worse mean rankings of target options when these were vegetarian, but not when target options were meat-based. This suggests meat options are preferred to equivalent vegetarian options and may be more likely to be selected. This has implications for interventions aiming to reduce meat consumption to make diets healthier and more sustainable.
Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells
Authors: Theodossiou Sophia K. , Murray Jett B. , Hold LeeAnn A. , Courtright Jeff M. , Carper Anne M. , Schiele Nathan R. 
Published: January 2021

AbstractBackgroundTissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited.MethodsMouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed.ResultsTGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling.ConclusionsThese findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.