bluuebunny/crossref_metadata_2025_split huggingface dataset:
Migraine Genetic Variants Influence Cerebral Blood Flow
Authors: Knol Maria J. , Loehrer Elizabeth A. , Wen Ke‐xin , Bos Daniel , Ikram M. Kamran , Vernooij Meike W. , Adams Hieab H.H. , Ikram M. Arfan 
Published: September 2019

ObjectiveTo investigate the association of migraine genetic variants with cerebral blood flow (CBF).BackgroundMigraine is a common disorder with many genetic and non‐genetic factors affecting its occurrence. The exact pathophysiological mechanisms underlying the disease remain unclear, but are known to involve hemodynamic and vascular disruptions. Recent genome‐wide association studies have identified 44 genetic variants in 38 genetic loci that affect the risk of migraine, which provide the opportunity to further disentangle these mechanisms.MethodsWe included 4665 participants of the population‐based Rotterdam Study (mean age 65.0 ± 10.9 years, 55.6% women). Cross‐sectional area (mm2), flow velocity (mm/s), and blood flow (mL/min) were measured in both carotids and the basilar artery using 2‐dimensional phase‐contrast magnetic resonance imaging. We analyzed 43 previously identified migraine variants separately and calculated a genetic risk score (GRS). To assess the association with CBF, we used linear regression models adjusted for age, sex, and total brain volume. Hierarchical clustering was performed based on the associations with CBF measures and tissue enrichment.ResultsThe rs67338227 risk allele was associated with higher flow velocity and smaller cross‐sectional area in the carotids (Pminimum = 3.7 × 10−8). Other variants were related to CBF with opposite directions of effect, but not significantly after multiple testing adjustments (P < 1.4 × 10−4). The migraine GRS was not associated with CBF after multiple testing corrections. Migraine risk variants were found to be enriched for flow in the basilar artery (λ = 2.39).ConclusionsThese findings show that genetic migraine risk is complexly associated with alterations in cerebral hemodynamics.
Stimulator of interferon genes agonists attenuate type I diabetes progression in NOD mice
Authors: Lemos Henrique , Mohamed Eslam , Huang Lei , Chandler Phillip R. , Ou Rong , Pacholczyk Rafal , Mellor Andrew L. 
Published: September 2019

AbstractReagents that activate the signaling adaptor stimulator of interferon genes (STING) suppress experimentally induced autoimmunity in murine models of multiple sclerosis and arthritis. In this study, we evaluated STING agonists as potential reagents to inhibit spontaneous autoimmune type I diabetes (T1D) onset in non‐obese diabetic (NOD) female mice. Treatments with DNA nanoparticles (DNPs), which activate STING when cargo DNA is sensed, delayed T1D onset and reduced T1D incidence when administered before T1D onset. DNP treatment elevated indoleamine 2,3 dioxygenase (IDO) activity, which regulates T‐cell immunity, in spleen, pancreatic lymph nodes and pancreas of NOD mice. Therapeutic responses to DNPs were partially reversed by inhibiting IDO and DNP treatment synergized with insulin therapy to further delay T1D onset and reduce T1D incidence. Treating pre‐diabetic NOD mice with cyclic guanyl‐adenyl dinucleotide (cGAMP) to activate STING directly delayed T1D onset and stimulated interferon‐αβ (IFN‐αβ), while treatment with cyclic diguanyl nucleotide (cdiGMP) did not delay T1D onset or induce IFN‐αβ in NOD mice. DNA sequence analyses revealed that NOD mice possess a STING polymorphism that may explain differential responses to cGAMP and cdiGMP. In summary, STING agonists attenuate T1D progression and DNPs enhance therapeutic responses to insulin therapy.
Effects of biogenetic beliefs for schizophrenia on potential caregivers in China: Exploring the role of affiliate stigma
Authors: Yao Xiaohui , Wang Chunhui , Zhu Zhigang , Hui Jianwen 
Published: September 2019

AbstractSchizophrenia affects more than eight million people in China. Stigmatization of schizophrenia may prevent family members and close others from providing social support to those with schizophrenia. This article aims to investigate the potential use of a biogenetic approach to reduce the stigma of schizophrenia using a cross‐sectional (study 1, n = 141) and an experimental design (study 2, n = 100) in China. In the first study, mediation analysis reveals that perceived affiliate stigma, the negative prejudice, and discrimination towards family members of individuals with socially stigmatized identities due to their affiliation with the person mediates the path between biogenetic beliefs and desire for social distance. This pattern is replicated in study 2 in which two 10‐min lectures were created and used to influence participants’ beliefs in biogenetic causes of schizophrenia. Findings suggest that the biogenetic approach may increase Chinese participants’ desired social distance towards their family members with schizophrenia through increasing their concerns about the negative consequences of being affiliated with the family member. Therefore, future research should investigate aspects of biogenetic anti‐stigma campaigns that do not increase participants’ perception of affiliate stigma in China.
Increased circulating IgG levels, myocardial immune cells and IgG deposits support a role for an immune response in pre‐ and end‐stage heart failure
Authors: van den Hoogen Patricia , de Jager Saskia C. A. , Huibers Manon M. H. , Schoneveld Arjan H. , Puspitasari Yustina M. , Valstar Gideon B. , Oerlemans Marish I. F. J. , de Weger Roel A. , Doevendans Pieter A. , den Ruijter Hester M. , Laman Jon D. , Vink Aryan , Sluijter Joost P. G. 
Published: September 2019

AbstractThe chronic inflammatory response plays an important role in adverse cardiac remodelling and the development of heart failure (HF). There is also evidence that in the pathogenesis of several cardiovascular diseases, chronic inflammation is accompanied by antibody and complement deposits in the heart, suggestive of a true autoimmune response. However, the role of antibody‐mediated immune responses in HF progression is less clear. We assessed whether immune cell infiltration and immunoglobulin levels are associated with HF type and disease stage, taking sex differences into account. We found IgG deposits and increased infiltration of immune cells in the affected myocardium of patients with end‐stage HF with reduced ejection fraction (HFrEF, n = 20). Circulating levels of IgG1 and IgG3 were elevated in these patients. Furthermore, the percentage of transitional/regulatory B cells was decreased (from 6.9% to 2.4%) compared with healthy controls (n = 5). Similarly, increased levels of circulating IgG1 and IgG3 were observed in men with left ventricular diastolic dysfunction (LVDD, n = 5), possibly an early stage of HF with preserved EF (HFpEF). In conclusion, IgG deposits and infiltrates of immune cells are present in end‐stage HFrEF. In addition, both LVDD patients and end‐stage HFrEF patients show elevated levels of circulating IgG1 and IgG3, suggesting an antibody‐mediated immune response upon cardiac remodelling, which in the early phase of remodelling appear to differ between men and women. These immunoglobulin subclasses might be used as marker for pre‐stage HF and its progression. Future identification of auto‐antigens might open possibilities for new therapeutic interventions.
Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling
Authors: Wang Yunjiao , He Gang , Wang Feng , Zhang Chenke , Ge Zilu , Zheng Xiaolong , Deng Honghao , Yuan Chengsong , Zhou Binghua , Tao Xu , Zhang Jiqiang , Tang Kanglai 
Published: September 2019

AbstractTendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti‐inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin‐treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO‐Ohpic and IGF‐1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down‐regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.
miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8
Authors: Fan Xinlong , Zhao Yuejiao 
Published: September 2019

AbstractDespite the increasing incidence of papillary thyroid cancer in the past decade, the molecular mechanism underlying its progression remains unknown. Several studies have reported down‐regulation of miR‐451a or circular miR‐451a in papillary thyroid cancer cell lines or patients. However, the underlying molecular mechanism remains unknown. In this study, we found that overexpression of miR‐451a could inhibit proliferation, epithelial‐mesenchymal transition and induce apoptosis in papillary thyroid cancer cells. Proteasome subunit beta type‐8 was predicted to be a direct target of miR‐451a and was validated with a luciferase reporter assay. Further functional assays showed that miR‐451a could inhibit thyroid cancer progression by targeting proteasome subunit beta type‐8.
Comparison of platelet‐rich fibrin and cellulose in palatal wounds after graft harvesting
Authors: Patarapongsanti Arada , Bandhaya Panwadee , Sirinirund Benyapha , Khongkhunthian Sakornratana , Khongkhunthian Pathawee 
Published: September 2019

AbstractAimThe aim of the present study was to compare patient morbidity and healing outcomes of free gingival graft (FGG) harvesting at palatal donor sites and after using platelet‐rich fibrin (PRF) and oxidized regenerated cellulose (ORC). FGG harvesting leaves open palatal wounds, which heal by secondary intention. Patients might experience discomfort or pain during the first 2 weeks of healing.MethodsEighteen participants requiring two FGG were recruited. The test and control sites were covered with PRF membrane and ORC. The complete epithelialization of the palatal wound, the percentage of wound healing, and postoperative pain were evaluated, 1, 3, and 7 days and 2, 3, and 4 weeks after surgery.ResultsSimilar wound size reduction at 1 week (test: 36.87%, control: 38.78%) was found. At 2 weeks, the majority of the test group (88.89%) showed complete epithelialization, whereas 66.67% of the control group had complete epithelialization (P = .228). Pain was more prevalent in the control group (27.77%) than in the test group (11.1%) on day 1. None of the participants reported any pain or discomfort at the test sites on day 3.ConclusionsPRF seems to reduce patient morbidity, but there is no difference in palatal wound healing (P > .05).
A novel 3‐oxoacyl‐ACP reductase (FabG3) is involved in the xanthomonadin biosynthesis of Xanthomonas campestris pv. campestris
Authors: Yu Yonghong , Ma Jianrong , Guo Qiaoqiao , Ma Jincheng , Wang Haihong 
Published: September 2019

SummaryXanthomonas campestris pv. campestris (Xcc), the causal agent of black rot in crucifers, produces a membrane‐bound yellow pigment called xanthomonadin to protect against photobiological and peroxidative damage, and uses a quorum‐sensing mechanism mediated by the diffusible signal factor (DSF) family signals to regulate virulence factors production. The Xcc gene XCC4003, annotated as Xcc fabG3, is located in the pig cluster, which may be responsible for xanthomonadin synthesis. We report that fabG3 expression restored the growth of the Escherichia coli fabG temperature‐sensitive mutant CL104 under non‐permissive conditions. In vitro assays demonstrated that FabG3 catalyses the reduction of 3‐oxoacyl‐acyl carrier protein (ACP) intermediates in fatty acid synthetic reactions, although FabG3 had a lower activity than FabG1. Moreover, the fabG3 deletion did not affect growth or fatty acid composition. These results indicate that Xcc fabG3 encodes a 3‐oxoacyl‐ACP reductase, but is not essential for growth or fatty acid synthesis. However, the Xcc fabG3 knock‐out mutant abolished xanthomonadin production, which could be only restored by wild‐type fabG3, but not by other 3‐oxoacyl‐ACP reductase‐encoding genes, indicating that Xcc FabG3 is specifically involved in xanthomonadin biosynthesis. Additionally, our study also shows that the Xcc fabG3‐disrupted mutant affects Xcc virulence in host plants.
Transcriptome reprogramming in the shoot apical meristem of CymRSV‐infected Nicotiana benthamiana plants associates with viral exclusion and the lack of recovery
Authors: Medzihradszky Anna , Gyula Péter , Sós‐Hegedűs Anita , Szittya György , Burgyán József 
Published: September 2019

SummaryIn some plant–virus interactions plants show a sign of healing from virus infection, a phenomenon called symptom recovery. It is assumed that the meristem exclusion of the virus is essential to this process. The discovery of RNA silencing provided a possible mechanism to explain meristem exclusion and recovery. Here we show evidence that silencing is not the reason for meristem exclusion in Nicotiana benthamiana plants infected with Cymbidium ringspot virus (CymRSV). Transcriptome analysis followed by in situ hybridization shed light on the changes in gene expression in the shoot apical meristem (SAM) on virus infection. We observed the down‐regulation of meristem‐specific genes, including WUSCHEL (WUS). However, WUS was not down‐regulated in the SAM of plants infected with meristem‐invading viruses such as turnip vein‐clearing virus (TVCV) and cucumber mosaic virus (CMV). Moreover, there is no connection between loss of meristem function and fast shoot necrosis since TVCV necrotized the shoot while CMV did not. Our findings suggest that the observed transcriptional changes on virus infection in the shoot are key factors in tip necrosis and symptom recovery. We observed a lack of GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE (GAPDH) expression in tissues around the meristem, which likely stops virus replication and spread into the meristem.
Early unplanned return visits to a pediatric emergency department in Israel
Authors: Reiser Or , Diamand Raz , Shavit Itai 
Published: September 2019

AbstractBackgroundEarly unplanned return visits (EURV) to the emergency department (ED) are stressful for children and caregivers. Dissatisfaction with the first ED visit could influence the decision to revisit the ED. The aim was to evaluate comprehensively parents’ satisfaction with the first ED visit.MethodsA prospective questionnaire‐based study of parents of EURV patients was conducted in a pediatric ED. Participants were enrolled based on convenience sampling. The study instrument was the parental satisfaction questionnaire (PSQ). The 27 PSQ items evaluate four themes related to satisfaction: attitude and respect, information provided, continuity of care, and waiting times. Items are rated on a five‐point Likert scale.ResultsDuring the 18‐month study, 101 parents of EURV patients were surveyed and 98 agreed to participate. On the return visit, 63 EURV patients were discharged and 35 EURV patients were hospitalized. Eighty‐seven (88.7%) caregivers scored an overall level of satisfaction with the first visit of 8–10 on a 10‐point Likert scale. Median scores in 22 PSQ items were 4 (interquartile range [IQR] 4–5) or 4 (IQR 3–4). Median scores for “physicians attention and answering questions and concern” and “physicians clear and understood explanations” were 3 (IQR 3–4) and 2 (IQR 2–3), respectively. The PSQ scores were similar for patients who were discharged on the return visit and patients who were hospitalized.ConclusionsParents were satisfied with the care provided at the first ED visit. There was a lower level of satisfaction with physician interaction.
The effects of bosentan on hyperoxia‐induced lung injury in neonatal rats
Authors: Özdemir Özmert MA , Taban Özgün , Enli Yaşar , Bir Ferda , Şahin Barbaros , Ergin Hacer 
Published: September 2019

AbstractBackgroundBronchopulmonary dysplasia (BPD) remains an important cause of morbidity and mortality in premature infants. There is currently no proven effective treatment modality for BPD, and inflammation and oxidative injury play an important role in the pathogenesis of this disease. This study investigated the histopathological and biochemical effects of bosentan, which is a non‐specific endothelin receptor antagonist with known antioxidant and anti‐inflammatory properties, on hyperoxia‐induced lung injury (HILI) in neonatal rats.MethodsThe experiment was performed on newborn rats from the 3rd to the 13th postnatal day. The rats were randomly divided into six groups: Group 1 (air‐exposed + saline, n = 6); Group 2 (HILI, n = 8); Group 3 (air‐exposed + bosentan, n = 7); Group 4 (HILI + saline, n = 7); Group 5 (HILI + early bosentan‐treated group, n = 6), and Group 6 (HILI + late bosentan‐treated group, n = 7). Bosentan was administered (30 mg/kg/day) intraperitoneally. The histopathological effects of bosentan on lung tissue were assessed by their alveolar surface area, fibrosis, and smooth muscle actin (SMA) scores, and the biochemical effects on lung tissue were assessed by interleukin‐1 beta (IL‐1β), IL‐6, IL‐10, and tumor necrosis factor‐alpha (TNF‐α).ResultsThe alveolar surface area and fibrosis scores were found to be significantly higher in HILI groups compared with Group 1 (P < 0.01). The SMA scores in HILI groups were also significantly higher than Group 1 (P < 0.01). Bosentan treatment, especially late therapy, reduced all of these histopathological scores and the levels of IL‐6 and TNF‐α in the hyperoxia groups (P < 0.01).ConclusionThis experimental study showed that bosentan had a protective effect on hyperoxic lung injury through its anti‐inflammatory properties.
Targeting the Motivated? Ethnicity and the Pre‐emptive Use of Government Repression
Authors: Beiser‐McGrath Janina 
Published: September 2019

AbstractResearch on government repression often focuses on the comparison between states over time and provides little insight about the targets of repression within a state. This article unpacks government repression against different ethnic groups. It argues that non‐democratic governments use pre‐emptive and targeted repression against ethnic groups that are discriminated, strong, or have a history of protest or rebellion in order to prevent future ethnic rebellions. For democratic governments, on the other hand, the cost of pre‐emptive repression is too high. The article tests this argument in a quantitative analysis of government‐group dyads. It finds at least partial support for some implications of the argument: Autocratic governments use more repression than democracies against discriminated groups, but only when they are also weak, and against groups with a history of protest. There is little evidence that regimes of either type respond to previous violent mobilization or group strength with repression.
Characterization of repeat arrays in ultra‐long nanopore reads reveals frequent origin of satellite DNA from retrotransposon‐derived tandem repeats
Authors: Vondrak Tihana , Ávila Robledillo Laura , Novák Petr , Koblížková Andrea , Neumann Pavel , Macas Jiří 
Published: September 2019

SummaryAmplification of monomer sequences into long contiguous arrays is the main feature distinguishing satellite DNA from other tandem repeats, yet it is also the main obstacle in its investigation because these arrays are in principle difficult to assemble. Here we explore an alternative, assembly‐free approach that utilizes ultra‐long Oxford Nanopore reads to infer the length distribution of satellite repeat arrays, their association with other repeats and the prevailing sequence periodicities. Using the satellite DNA‐rich legume plant Lathyrus sativus as a model, we demonstrated this approach by analyzing 11 major satellite repeats using a set of nanopore reads ranging from 30 to over 200 kb in length and representing 0.73× genome coverage. We found surprising differences between the analyzed repeats because only two of them were predominantly organized in long arrays typical for satellite DNA. The remaining nine satellites were found to be derived from short tandem arrays located within LTR‐retrotransposons that occasionally expanded in length. While the corresponding LTR‐retrotransposons were dispersed across the genome, this array expansion occurred mainly in the primary constrictions of the L. sativus chromosomes, which suggests that these genome regions are favourable for satellite DNA accumulation.
A Course-Based Undergraduate Research Experience in Biofluid Mechanics
Authors: Clyne Alisa Morss , Shieh Adrian C. , Stanford Jennifer S. 
Published: September 2019

Abstract
Course-based undergraduate research experiences (CURE) are a valuable tool to increase research exposure for larger undergraduate cohorts. We implemented a CURE within a senior-level biofluid mechanics course that was primarily taught using a flipped classroom approach. Due to the large class size, the students analyzed data that was publicly available and produced by one of our laboratories. Student teams then developed hypotheses based on the data analysis and designed a set of in vitro and in vivo experiments to test those hypotheses. The hypotheses and experiments that were most highly rated by the class were then tested in our laboratory. At the end of the class, student gains were assessed by self-report and compared to those self-reported by students engaging in a traditional freshman undergraduate summer research experience. While the students in the CURE reported moderate gains in self-assessment of research-based skills, their self-reported gains were statistically significantly lower than those reported by students who participated in the traditional research experience. We believe that the CURE could be improved through implementation in a lower level class, enabling students to observe laboratory experiments, and providing additional feedback throughout the hypothesis development and experimental design process. Overall, the CURE is an innovative way to expand research experiences, in particular for engineering students who often do not participate in hypothesis-driven research during their undergraduate education.