bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding the missing link: when community-based outreach in public space is key to engage migrants in health prevention programmes in Paris, France
Authors: Gosselin Anne , Coulibaly Karna , Ravalihasy Andrainolo , Carillon Séverine , Ridde Valéry , Derche Nicolas , Mbiribindi Romain , Desgrées du Loû Annabel 
Published: April 2020

BackgroundOne of the classic challenges for prevention programmes is reaching the populations they serve. In France, a substantial number of African migrants living with HIV acquired their infection after migrating. The aim of this paper is to better understand the characteristics of the population reached by a community-based outreach approach.MethodsWe compared sociodemographic characteristics across three different groups in the Paris greater area: (1) the general African migrant population (Population census), (2) the African migrant population using either the regular healthcare system or the system for vulnerable populations (PARCOURS Survey) and (3) the African migrant population reached through a community-based mobile unit (Afrique Avenir). Comparisons were conducted according to sex, age, region of origin, duration of residence and occupational and legal statuses using χ2tests.ResultsThe migrants reached by the mobile unit were mostly men (69%), 52% of whom were younger than 35 years old. They more often lived in precarious situations than did the general sub-Saharan population (49% vs 35% were unemployed, respectively, p<0.001) and the ones accessing the regular healthcare system. Fewer of them lived in precarious situations than did migrants seeking healthcare consultations for vulnerable populations (42% in the mobile unit vs 54% in healthcare consultations were undocumented, p<0.028).ConclusionOur study shows that the outreach approach can constitute a missing link in the prevention chain among sub-Saharan African migrants, reaching a group that differs from the general migrant population and from the migrant population in healthcare services—not only the newly arrived migrants who live in more precarious situations but also those who have been in France for several years and are still affected by social hardship.
Incomplete Freund’s adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment
Authors: Pollack Karlyn E , Meneveau Max O , Melssen Marit M , Lynch Kevin T , Koeppel Alexander F , Young Samuel J , Turner Stephen , Kumar Pankaj , Sol-Church Katia , Mauldin Ileana S , Slingluff Jr Craig L 
Published: April 2020

BackgroundImmunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund’s adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME.MethodsBiopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3. Controls included normal skin and skin injected with IFA without peptides. Gene expression analysis was performed by RNAseq.ResultsVSME samples were evaluated from 27 patients. One vaccine with peptides in pICLC+IFA enhanced expression of CD80, CD83, CD86 (p<0.01), CD40 and CD40L (p<0.0001) over normal skin; these effects were significantly enhanced for SSV with peptides+IFA. Vaccines containing pICLC increased expression of TBX21 (T-bet) but did not decrease GATA3 over normal skin, whereas SSV with peptides in IFA dramatically enhanced TBX21 and decreased GATA3, with high expression of IFNγ and STAT1. SSV with peptides in IFA also reduced arginase-1 (ARG1) expression and enhanced expression of TLR adapter molecules TICAM-1 (TRIF) and MYD88. Furthermore, SSV with IFA and peptides also enhanced expression of chemokines associated with TLS formation.ConclusionsThese findings suggest that SSV with peptides in IFA enhances CD40L expression by CD4 T cells, supports a Th1 microenvironment, with accumulation of activated and mature DC. Increased expression of TLR adaptor proteins after SSV with peptides in IFA might implicate effects of the skin microbiome. Reduced ARG1 may reflect diminished suppressive myeloid activity in the VSME.Trial registration number(NCT00705640,NCT01585350).
Late Neoproterozoic–Silurian tectonic evolution of the Rödingsfjället Nappe Complex, orogen-scale correlations and implications for the Scandian suture
Authors: Slagstad Trond , Saalmann Kerstin , Kirkland Chris L. , Høyen Anne B. , Storruste Bergliot K. , Coint Nolwenn , Pin Christian , Marker Mogens , Bjerkgård Terje , Krill Allan , Solli Arne , Boyd Rognvald , Angvik Tine Larsen , Larsen Rune B. 
Published: April 2020

Abstract
The Scandinavian Caledonides consist of disparate nappes of Baltican and exotic heritage, thrust southeastwards onto Baltica during the Mid-Silurian Scandian continent–continent collision, with structurally higher nappes inferred to have originated at increasingly distal positions to Baltica. New U–Pb zircon geochronological and whole-rock geochemical and Sm–Nd isotopic data from the Rödingsfjället Nappe Complex reveal 623 Ma high-grade metamorphism followed by continental rifting and emplacement of the Umbukta gabbro at 578 Ma, followed by intermittent magmatic activity at 541, 510, 501, 484 and 465 Ma. Geochemical data from the 501 Ma Mofjellet Group is indicative of arc magmatism at this time. Syntectonic pegmatites document pre-Scandian thrusting at 515 and 475 Ma, and Scandian thrusting at 429 Ma. These results document a tectonic history that is compatible with correlation with peri-Laurentian and/or peri-Gondwanan terranes. The data allow correlation with nappes at higher and lower tectonostratigraphic levels, including at least parts of the Helgeland, Kalak and Seve nappe complexes, implying that they too may be exotic to Baltica. Neoproterozoic fragmentation of the hypothesized Rodinia supercontinent probably resulted in numerous coeval, active margins, producing a variety of peri-continental terranes that can only be distinguished through further combined geological, palaeomagnetic and palaeontological investigations.
Transfer of MicroRNA via Macrophage-Derived Extracellular Vesicles Promotes Proneural-to-Mesenchymal Transition in Glioma Stem Cells
Authors: Zhang Zongpu , Xu Jianye , Chen Zihang , Wang Huizhi , Xue Hao , Yang Chunlei , Guo Qindong , Qi Yanhua , Guo Xiaofan , Qian Mingyu , Wang Shaobo , Qiu Wei , Gao Xiao , Zhao Rongrong , Guo Xing , Li Gang 
Published: April 2020

Abstract
Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages triggered PMT in glioma stem cells (GSC) via small extracellular vesicles (sEV). sEVs from monocyte-derived macrophages transferred miR-27a-3p, miR-22-3p, and miR-221-3p to GSCs, and these miRNAs promoted several mesenchymal phenotypes in proneural (PN) GSCs by simultaneously targeting CHD7. We found that CHD7 played a critical role in the maintenance of the PN phenotype, and CHD7 knockdown significantly promoted PMT in GSCs via the RelB/P50 and p-STAT3 pathways. The induction of PMT by sEVs containing miR-27a-3p, miR-22-3p, and miR-221-3p in a xenograft nude mouse model exacerbated radiotherapy resistance and thus decreased the benefits of radiotherapy. Collectively, these findings identified macrophage-derived sEVs as key regulators of PMT in GSCs and demonstrated that CHD7 is a novel inhibitor of PMT.
Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection
Authors: Saleh Moussa , Gabriels James , Chang David , Soo Kim Beom , Mansoor Amtul , Mahmood Eitezaz , Makker Parth , Ismail Haisam , Goldner Bruce , Willner Jonathan , Beldner Stuart , Mitra Raman , John Roy , Chinitz Jason , Skipitaris Nicholas , Mountantonakis Stavros , Epstein Laurence M. 
Published: April 2020

Background:
The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death.

Methods:
Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death.

Results:

Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms,
P
=0.834). The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms,
P
=0.004). Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation. No arrhythmogenic deaths were reported.

Conclusions:
In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.
ZO-1 Regulates Intercalated Disc Composition and Atrioventricular Node Conduction
Authors: Dai Wenli , Nadadur Rangarajan D. , Brennan Jaclyn A. , Smith Heather L. , Shen Kaitlyn M. , Gadek Margaret , Laforest Brigitte , Wang Mingyi , Gemel Joanna , Li Ye , Zhang Jing , Ziman Bruce D. , Yan Jiajie , Ai Xun , Beyer Eric C. , Lakata Edward G. , Kasthuri Narayanan , Efimov Igor R. , Broman Michael T. , Moskowitz Ivan P. , Shen Le , Weber Christopher R. 
Published: April 2020

Rationale:

ZO-1 (Zona occludens 1), encoded by the tight junction protein 1 (
TJP1
) gene, is a regulator of paracellular permeability in epithelia and endothelia. ZO-1 interacts with the actin cytoskeleton, gap, and adherens junction proteins and localizes to intercalated discs in cardiomyocytes. However, the contribution of ZO-1 to cardiac physiology remains poorly defined.

Objective:
We aim to determine the role of ZO-1 in cardiac function.

Methods and Results:

Inducible cardiomyocyte-specific
Tjp1
deletion mice (
Tjp1

fl/fl

;
Myh6

Cre/Esr1*

) were generated by crossing the
Tjp1
floxed mice and
Myh6

Cre/Esr1*

transgenic mice. Tamoxifen-induced loss of ZO-1 led to atrioventricular (AV) block without changes in heart rate, as measured by ECG and ex vivo optical mapping. Mice with tamoxifen-induced conduction system-specific deletion of
Tjp1
(
Tjp1

fl/fl

; Hcn4

CreERt2

) developed AV block while tamoxifen-induced conduction system deletion of
Tjp1
distal to the AV node (
Tjp1

fl/fl

; Kcne1

CreERt2

) did not demonstrate conduction defects. Western blot and immunostaining analyses of AV nodes showed that ZO-1 loss decreased Cx (connexin) 40 expression and intercalated disc localization. Consistent with the mouse model study, immunohistochemical staining showed that ZO-1 is abundantly expressed in the human AV node and colocalizes with Cx40. Ventricular conduction was not altered despite decreased localization of ZO-1 and Cx43 at the ventricular intercalated disc and modestly decreased left ventricular ejection fraction, suggesting ZO-1 is differentially required for AV node and ventricular conduction.

Conclusions:
ZO-1 is a key protein responsible for maintaining appropriate AV node conduction through maintaining gap junction protein localization.
Behavioural and physiological responses to simulated predator-induced stress in the eastern box turtle, Terrapene carolina carolina
Authors: Preston Victoria L. , Vannatta Jessica M. , Klukowski Matthew 
Published: April 2020

Abstract
In spite of the fully-hinged shell being the defining characteristic of box turtles, few studies have quantified the behavioural use of the shell in response to predator encounters. While it is often assumed that box turtles simply withdraw into their shell in response to threats, we expected variability among individuals in shell usage and in the degree of head and limb retraction because withdrawal is likely to be costly. We tested the behavioural and physiological responses of free-ranging eastern box turtles to stimuli of varying intensity: observation only, a visual stimulus, a poke on the leg, or a pinch on the leg before being flipped. The more intense the simulated predatory stimulus, the more likely turtles were to fully close their shell. However, stimulus intensity did not affect plasma corticosterone or lactate levels. This may be due to too brief or weak of a stimulus, increased parasympathetic activity, or seasonal effects. Upon capture and during handling, almost all turtles withdrew into their shells and closed their anterior plastron, although fewer closed their posterior plastron, and a few engaged in other behaviours such as biting and urinating. Older, larger turtles were able to close their shells with greater strength than younger and smaller turtles. Our results indicate that in spite of their fully closable shell, box turtles exhibit a graded response to perceived threats. This suggests that full closure of the shell is likely to be costly and occurs only in response to the most intense stimuli.
Limitations to Freedom of Religion or Belief in Denmark
Authors: Lassen Eva Maria 
Published: April 2020

Abstract
The article analyses legislative changes in the area of freedom of religion or belief in Denmark between 2014 and 2018. Recent legislation has placed pressure particularly on religious minorities to limit certain religious manifestations, and it is possible to trace a certain “juridification” of freedom of religion, by which the values underlying freedom of religion according to international standards are not always fully reflected. Additionally, there is a tendency to address societal concerns by means of legal interventions. The article argues that by making increased use of soft law developed by the EU, the Council of Europe and the UN, Danish lawmakers would be able to reach a more comprehensive understanding of freedom of religion or belief as well as include non-legal solutions to societal concerns. It further argues that while Denmark’s national (Lutheran) church possess the majority of constituents, nonetheless its privileged position may paradoxically strengthen freedom of religion for religious minorities.
A Numerical Study on the Influences of Sumatra Topography and Synoptic Features on Tropical Cyclone Formation over the Indian Ocean
Authors: Wang Chung-Chieh , Ma Shin-Kai , Johnson Richard H. 
Published: April 2020

Abstract
Spanning across the equator with a northwest–southeast orientation, the island of Sumatra can exert significant influences on low-level flow. Under northeasterly flow, in particular, lee vortices can form and some of them may subsequently develop into tropical cyclones (TCs) in the Indian Ocean (IO). Building upon the recent work of Fine et al., this study investigates the roles of the Sumatra topography and other common features on the formation of selected cases for analysis and numerical experiments. Four cases in northern IO were selected for analysis and two of them [Nisha (2008) and Ward 2009)] for simulation at a grid size of 4 km. Sensitivity tests without the Sumatra topography were also performed. Our results indicate that during the lee stage, most pre-TC vortices tend to be stronger with a clearer circulation when the topography is present. However, the island’s terrain is a helpful but not a deciding factor in TC formation. Specifically, the vortices in the no-terrain tests also reach TC status, but just at a later time. Some common ingredients contributing to a favorable environment for TC genesis are identified. They include northeasterly winds near northern Sumatra, westerly wind bursts along the equator, and migratory disturbances (TC remnants or Borneo vortices) to provide additional vorticity/moisture from the South China Sea. These factors also appear in most of the 22 vortices in northern IO during October–December in 2008 and 2009. For the sole case (Cleo) examined in southern IO, the deflection of equatorial westerlies into northwesterlies by Sumatra (on the windward side) is also helpful to TC formation.
How short is too short? A randomised controlled trial evaluating short-term existential behavioural therapy for informal caregivers of palliative patients
Authors: Kühnel Martina B , Marchioro Linda , Deffner Veronika , Bausewein Claudia , Seidl Hildegard , Siebert Sarah , Fegg Martin 
Published: April 2020

Background: Informal caregivers of palliative patients show higher levels of depression and distress compared with the general population. Fegg’s (2013) existential behavioural therapy was shortened to two individual 1-h sessions (short-term existential behavioural therapy). Aim: Testing the effectiveness of sEBT on psychological symptoms of informal caregivers in comparison with active control. Design: Randomised controlled trial. Setting/participants: Informal caregivers of palliative in-patients. Methods: The primary outcome was depression; secondary outcomes were anxiety, subjective distress and minor mental disorders, positive and negative affect, satisfaction with life, quality of life and direct health care costs. General linear mixed models allow several measurements per participant and change over time. Reasons for declining the intervention were investigated by Rosenstock’s Health Belief Model. Results: Overall inclusion rate was 41.0%. Data of 157 caregivers were available (63.1% females; mean age: 54.6 years, standard deviation (SD): 14.1); 127 participants were included in the main analysis. Participation in sEBT or active control was not significantly associated with post-treatment depression. Outcomes showed prevailingly significant association with time of investigation. Self-efficacy, scepticism of benefit of the intervention, belief of better coping alone and support by family and friends were significant factors in declining participation in the randomised controlled trial. Conclusion: Inclusion rate was tripled compared with a previously evaluated longer EBT group intervention. By shortening the intervention, inclusion rate was traded for effectiveness and the intervention could not impact caregivers’ psychological state. Early integration of sEBT and combination of individual and group setting and further study of the optimal length for caregiver interventions are suggested.
Economic evaluation of a combined screening and stepped-care treatment program targeting psychological distress in patients with metastatic colorectal cancer: A cluster randomized controlled trial
Authors: El Alili Mohamed , Schuurhuizen Claudia S.E.W , Braamse Annemarie M.J. , Beekman Aartjan T.F. , van der Linden Mecheline H. , Konings Inge R. , Dekker Joost , Bosmans Judith E. 
Published: April 2020

Background: Psychological distress is highly prevalent among patients with metastatic colorectal cancer. Aims: To perform an economic evaluation of a combined screening and treatment program targeting psychological distress in patients with metastatic colorectal cancer in comparison with usual care. Design: Societal costs were collected alongside a cluster randomized controlled trial for 48 weeks. A total of 349 participants were included. Setting: Participants were recruited from oncology departments at 16 participating hospitals in the Netherlands. Methods: Outcome measures were the Hospital Anxiety and Depression Scale and quality-adjusted life-years. Missing data were imputed using multiple imputation. Uncertainty was estimated using bootstrapping. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty surrounding the cost-effectiveness estimates. Sensitivity analyses were performed to check robustness of results. Results: Between treatment arms, no significant differences were found in Hospital Anxiety and Depression Scale score (mean difference: –0.058; 95% confidence interval: –0.13 to 0.011), quality-adjusted life-years (mean difference: 0.042; 95% confidence interval: –0.015 to 0.099), and societal costs (mean difference: –1152; 95% confidence interval: –5058 to 2214). Cost-effectiveness acceptability curves showed that the probability of cost-effectiveness was 0.64 and 0.74 at willingness-to-pay values of €0 and €10,000 per point improvement on the Hospital Anxiety and Depression Scale, respectively. The probability that the intervention was cost-effective compared to usual care for quality-adjusted life-years was 0.64 and 0.79 at willingness-to-pay values of €0 and €20,000 per quality-adjusted life-year, respectively. Conclusion: The intervention is dominant over usual care, primarily due to lower costs in the intervention group. However, there were no statistically significant differences in clinical effects and the uptake of the intervention was quite low. Therefore, widespread implementation cannot be recommended.
Endoscopic endonasal open reduction for fractures of the frontal process of the maxilla
Authors: Meng Xiangming , Wen Qingbo , Gu Jianhong , Wang Yangyang 
Published: April 2020

Objective This study was performed to evaluate the clinical efficacy of endoscopic endonasal open reduction of fractures of the frontal process of the maxilla (FFPM). Methods We performed a retrospective study of patients who underwent endoscopic endonasal open reduction of FFPM from December 2013 to October 2018. The preoperative assessment included nasal endoscopy, computed tomography imaging, and three-dimensional craniofacial reconstruction. The clinical results were evaluated with a visual analog scale at 2 days and 1 year postoperatively. Results Thirty-two patients (25 male, 7 female) with an average age of 39 years were included in the study. All patients successfully underwent a surgical operation via the endoscopic endonasal approach with a nasal mucosal incision, and the nasal deformities were corrected. At the 1-year follow-up, six (18.8%) and 26 (81.2%) patients were somewhat satisfied and very satisfied with the aesthetic result, respectively, and five (15.6%) and 27 (84.4%) were somewhat satisfied and very satisfied with the functional result, respectively. Conclusion Endoscopic endonasal open reduction can be considered a reliable method for anatomical reduction of FFPM. This technology provides a viable choice for the treatment of FFPM.