bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cohort profile: the ChicagO Multiethnic Prevention and Surveillance Study (COMPASS)
Authors: Aschebrook-Kilfoy Briseis , Kibriya Muhammad G , Jasmine Farzana , Stepniak Liz , Gopalakrishnan Rajan , Craver Andrew , Zakin Paul , Tasmin Saira , Kim Karen E , Goss Kathleen H , List Marcy , LeBeau Michelle , Ahsan Habibul 
Published: September 2020

PurposeThe ChicagO Multiethnic Prevention and Surveillance Study or ‘COMPASS’ is a population-based cohort study with a goal to examine the risk and determinants of cancer and chronic disease. COMPASS aims to address factors causing and/or exacerbating health disparities using a precision health approach by recruiting diverse participants in Chicago, with an emphasis on those historically underrepresented in biomedical research.ParticipantsNearly 8000 participants have been recruited from 72 of the 77 Chicago community areas. Enrolment entails the completion of a 1-hour long survey, consenting for past and future medical records from all sources, the collection of clinical and physical measurement data and the on-site collection of biological samples including blood, urine and saliva. Indoor air monitoring data and stool samples are being collected from a subset of participants. On collection, all biological samples are processed and aliquoted within 24 hours before long-term storage and subsequent analysis.Findings to dateThe cohort reported an average age of 53.7 years, while 80.5% identified as African-American, 5.7% as Hispanic and 47.8% as men. Over 50% reported earning less than US$15 000 yearly, 35% were obese and 47.8% were current smokers. Moreover, 38% self-reported having had a diagnosis of hypertension, while 66.4% were measured as hypertensive at enrolment.Future plansWe plan to expand recruitment up to 100 000 participants from the Chicago metropolitan area in the next decade using a hybrid community and clinic-based recruitment framework that incorporates data collection through mobile medical units. Follow-up data collection from current cohort members will include serial samples, as well as longitudinal health, lifestyle and behavioural assessment. We will supplement self-reported data with electronic medical records, expand the collection of biometrics and biosamples to facilitate increasing digital epidemiological study designs and link to state and/or national level databases to ascertain outcomes. The results and findings will inform potential opportunities for precision disease prevention and mitigation in Chicago and other urban areas with a diverse population.RegistrationNA.
“It’s not just hacking for the sake of it”: a qualitative study of health innovators’ views on patient-driven open innovations, quality and safety
Authors: Rivard Lysanne , Lehoux Pascale , Alami Hassane 
Published: September 2020

BackgroundOpen do-it-yourself (DIY) health innovations raise new dilemmas for patient-oriented and service-oriented scholars and healthcare providers. Our study aimed to generate practical insights into quality and safety issues to patient care raised by two volunteer-run, open DIY solutions: Nightscout Project (patient-driven, open-source software for type 1 diabetes management) and e-NABLE (volunteers who design and three-dimensionally print upper-limb assistive devices). To this end, we examined the views of health innovators who are knowledgeable about medical devices standards and regulations.MethodsWe applied a multimedia-based, data-elicitation technique to conduct indepth interviews with a diversified sample of 31 health innovators practising in two Canadian provinces (Quebec and Ontario). An exploratory thematic analysis approach was used to identify respondents’ reasoning processes and compare their overall judgements of Nightscout and e-NABLE.ResultsRespondents pondered the following quality and safety issues: importance of the need addressed; accessibility; volunteers’ ability to develop and maintain a safe solution of good quality; risks involved for users; consequences of not using the solution; and liability. Overall, innovators see Nightscout as a high-risk DIY solution that requires expert involvement and e-NABLE as a low-risk one that fills a hard-to-meet gap.ConclusionHealth innovators generally support patient-driven initiatives but also call for the involvement of professionals who possess complementary skills and knowledge. Our findings provide a list of issues healthcare providers may discuss with patients during clinical consultations to document potential risks and benefits of open DIY solutions. To inform new policy approaches, we propose the development of publicly funded umbrella organisations to act as intermediaries between open DIY solutions and regulatory bodies to help them meet quality and safety standards.
Incidence, predictors, and prognostic impact of recurrent acute myocardial infarction in China
Authors: Song Jiali , Murugiah Karthik , Hu Shuang , Gao Yan , Li Xi , Krumholz Harlan M , Zheng Xin 
Published: September 2020

BackgroundIncidence, predictors, and prognostic impact of recurrent acute myocardial infarction (AMI) after initial AMI remain poorly understood. Data on recurrent AMI in China is unknown.MethodsUsing the China Patient-centred Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study, we studied 3387 patients admitted to 53 hospitals for AMI and discharged alive. The association of recurrent AMI with 1-year mortality was evaluated using time-dependent Cox regression. Recurrent AMI events were classified as early (1–30 days), late (31–180 days), and very late (181–365 days). Their impacts on 1-year mortality were estimated by Kaplan-Meier methodology and compared by the log-rank test. Multivariable modelling was used to identify factors associated with recurrent AMI.ResultsThe mean (SD) age was 60.7 (11.9) years and 783 (23.1%) were women. The observed 1-year recurrent AMI rate was 2.5% (95% CI 2.00 to 3.07) with 35.7% events occurring within the first 30 days. Recurrent AMI was associated with 1-year mortality with an adjusted HR of 25.42 (95% CI 15.27 to 42.34). Early recurrent AMI was associated with the highest 1-year mortality rate of 53.3% (log-rank p<0.001). Predictors of recurrent AMI included age 75–84, in-hospital percutaneous coronary intervention, heart rate >90 min/beats at initial admission, renal dysfunction, and not being prescribed any of guideline-based medications at discharge.ConclusionsOne-third of recurrent AMI events occurred early. Recurrent AMI is strongly associated with 1-year mortality, particularly if early. Heightened surveillance during this early period and improving prescription of recommended discharge medications may reduce recurrent AMI in China.
Modulating TNFα activity allows transgenic IL15-Expressing CLL-1 CAR T cells to safely eliminate acute myeloid leukemia
Authors: Ataca Atilla Pinar , McKenna Mary K , Tashiro Haruko , Srinivasan Madhuwanti , Mo Feiyan , Watanabe Norihiro , Simons Brian Wesley , McLean Stevens Alexandra , Redell Michele S , Heslop Helen E , Mamonkin Maksim , Brenner Malcolm K , Atilla Erden 
Published: September 2020

BackgroundC-type lectin-like molecule 1 (CLL-1) is highly expressed in acute myeloid leukemia (AML) but is absent in primitive hematopoietic progenitors, making it an attractive target for a chimeric antigen receptor (CAR) T-cell therapy. Here, we optimized our CLL-1 CAR for anti-leukemic activity in mouse xenograft models of aggressive AML.MethodsFirst, we optimized the CLL-1 CAR using different spacer, transmembrane and costimulatory sequences. We used a second retroviral vector to coexpress transgenic IL15. We measured the effects of each construct on T cell phenotype and sequential (recursive) co culture assays with tumor cell targets to determine the durability of the anti tumor activity by flow cytometry. We administered CAR T cells to mice engrafted with patient derived xenografts (PDX) and AML cell line and determined anti tumor activity by bioluminescence imaging and weekly bleeding, measured serum cytokines by multiplex analysis. After euthanasia, we examined formalin-fixed/paraffin embedded sections. Unpaired two-tailed Student’s t-tests were used and values of p<0.05 were considered significant. Survival was calculated using Mantel-Cox log-rank test.ResultsIn vitro, CLL-1 CAR T cells with interleukin-15 (IL15) were less terminally differentiated (p<0.0001) and had superior expansion compared with CD28z-CD8 CAR T cells without IL15 (p<0.001). In both AML PDX and AML cell line animal models, CLL-1 CAR T coexpressing transgenic IL15 initially expanded better than CD28z-CD8 CAR T without IL15 (p<0.0001), but produced severe acute toxicity associated with high level production of human tumor necrosis factor α (TNFα), IL15 and IL2. Histopathology showed marked inflammatory changes with tissue damage in lung and liver. This acute toxicity could be managed by two strategies, individually or in combination. The excessive TNF alpha secretion could be blocked with anti-TNF alpha antibody, while excessive T cell expansion could be arrested by activation of an inducible caspase nine safety switch by administration of dimerizing drug. Both strategies successfully prolonged tumor-free survival.ConclusionCombinatorial treatment with a TNFα blocking antibody and subsequent activation of the caspase-9 control switch increased the expansion, survival and antileukemic potency of CLL-1 CAR T-cells expressing transgenic IL15 while avoiding the toxicities associated with excessive cytokine production and long-term accumulation of activated T-cells.
Boundary conditions for dynamic wetting - A mathematical analysis
Authors: Fricke Mathis , Bothe Dieter 
Published: September 2020

AbstractThe moving contact line paradox discussed in the famous paper by Huh and Scriven has lead to an extensive scientific discussion about singularities in continuum mechanical models of dynamic wetting in the framework of the two-phase Navier–Stokes equations. Since the no-slip condition introduces a non-integrable and therefore unphysical singularity into the model, various models to relax the singularity have been proposed. Many of the relaxation mechanisms still retain a weak (integrable) singularity, while other approaches look for completely regular solutions with finite curvature and pressure at the moving contact line. In particular, the model introduced recently in [A.V. Lukyanov, T. Pryer, Langmuir 33, 8582 (2017)] aims for regular solutions through modified boundary conditions. The present work applies the mathematical tool of compatibility analysis to continuum models of dynamic wetting. The basic idea is that the boundary conditions have to be compatible at the contact line in order to allow for regular solutions. Remarkably, the method allows to compute explicit expressions for the pressure and the curvature locally at the moving contact line for regular solutions to the model of Lukyanov and Pryer. It is found that solutions may still be singular for the latter model.
Steady moving contact line of water over a no-slip substrate
Authors: Lācis Uǧis , Johansson Petter , Fullana Tomas , Hess Berk , Amberg Gustav , Bagheri Shervin , Zaleski Stephané 
Published: September 2020

AbstractThe movement of the triple contact line plays a crucial role in many applications such as ink-jet printing, liquid coating and drainage (imbibition) in porous media. To design accurate computational tools for these applications, predictive models of the moving contact line are needed. However, the basic mechanisms responsible for movement of the triple contact line are not well understood but still debated. We investigate the movement of the contact line between water, vapour and a silica-like solid surface under steady conditions in low capillary number regime. We use molecular dynamics (MD) with an atomistic water model to simulate a nanoscopic drop between two moving plates. We include hydrogen bonding between the water molecules and the solid substrate, which leads to a sub-molecular slip length. We benchmark two continuum methods, the Cahn–Hilliard phase-field (PF) model and a volume-of-fluid (VOF) model, against MD results. We show that both continuum models reproduce the statistical measures obtained from MD reasonably well, with a trade-off in accuracy. We demonstrate the importance of the phase-field mobility parameter and the local slip length in accurately modelling the moving contact line.
Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML
Authors: Li Sheng , Chen Xiaowen , Wang Jiahui , Meydan Cem , Glass Jacob L. , Shih Alan H. , Delwel Ruud , Levine Ross L. , Mason Christopher E. , Melnick Ari M. 
Published: September 2020

Abstract

Epigenetic allele diversity is linked to inferior prognosis in acute myeloid leukemia (AML). However, the source of epiallele heterogeneity in AML is unknown. Herein we analyzed epiallele diversity in a genetically and clinically annotated AML cohort. Notably, AML driver mutations linked to transcription factors and favorable outcome are associated with epigenetic destabilization in a defined set of susceptible loci. In contrast, AML subtypes linked to inferior prognosis manifest greater abundance and highly stochastic epiallele patterning. We report an epiallele outcome classifier supporting the link between epigenetic diversity and treatment failure. Mouse models with TET2 or IDH2 mutations show that epiallele diversity is especially strongly induced by IDH mutations, precedes transformation to AML, and is enhanced by cooperation between somatic mutations. Furthermore, epiallele complexity was partially reversed by epigenetic therapies in AML driven by TET2/IDH2, suggesting that epigenetic therapy might function in part by reducing population complexity and fitness of AMLs.

Significance:
We show for the first time that epigenetic clonality is directly linked to specific mutations and that epigenetic allele diversity precedes and potentially contributes to malignant transformation. Furthermore, epigenetic clonality is reversible with epigenetic therapy agents.
This article is highlighted in the In This Issue feature, p. 1775
Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers
Authors: Song Xinxin , Zhou Zhuan , Li Hongchun , Xue Yifan , Lu Xinghua , Bahar Ivet , Kepp Oliver , Hung Mien-Chie , Kroemer Guido , Wan Yong 
Published: September 2020

Abstract

Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells. NGI-1, which inhibits B7-H4 glycosylation causing its ubiquitination and subsequent degradation, improves the immunogenic properties of cancer cells treated with doxorubicin, enhancing their phagocytosis by dendritic cells and their capacity to elicit CD8+ IFNγ-producing T-cell responses. In preclinical models of TNBC, a triple combination of NGI-1, camsirubicin (a noncardiotoxic doxorubicin analogue) and PD-L1 blockade was effective in reducing tumor growth. Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule B7-H4.

Significance:
This work unravels the regulation of B7-H4 stability by ubiquitination and glycosylation, which affects tumor immunogenicity, particularly regarding immune-cold breast cancers. The inhibition of B7-H4 glycosylation can be favorably combined with immunogenic chemotherapy and PD-L1 blockade to achieve superior immuno-infiltration of cold tumors, as well as improved tumor growth control.
See related commentary by Pearce and Läubli, p. 1789.
This article is highlighted in the In This Issue feature, p. 1775
A presença dos clássicos na arte escultórica de João Turin e a identidade paranaense
Authors: Fonseca Barbara 
Published: September 2020

A partir das ideias do historiador britânico Martin Bernal, entendemos a presença do passado antigo nas políticas da modernidade e percebemos que esse é moldado conforme o seu momento histórico. Assim, notando a presença de elementos greco-romanos no Movimento Paranista, nos questionamos de que maneira a cultura clássica influenciou e foi usada na construção da identidade paranaense do início do século XX. Para tanto, analisamos a revista Illustração Paranaense, principal meio de comunicação entre a elite curitibana e destacamos João Turin como um dos principais artista do movimento, autor de obras em que se combinam os elementos paranaenses e greco-romanos. Dessa forma, no presente artigo, focamos na obra Columna Paranaense, criada por Turin, a fim de responder em que medida o uso da arte greco-romana em território paranaense serviu para exaltar o novo comportamento e a identidade paranista.
Reciprocal Interaction Between Pericytes and Macrophage in Poststroke Tissue Repair and Functional Recovery
Authors: Shibahara Tomoya , Ago Tetsuro , Tachibana Masaki , Nakamura Kuniyuki , Yamanaka Kei , Kuroda Junya , Wakisaka Yoshinobu , Kitazono Takanari 
Published: September 2020

Background and Purpose:
Poststroke tissue repair, comprised of macrophage-mediated clearance of myelin debris and pericyte-mediated fibrotic response within the infarct area, is an important process for functional recovery. Herein, we investigated the reciprocal interaction between pericytes and macrophages during poststroke repair and functional recovery.

Methods:

We performed a permanent middle cerebral artery occlusion in both wild-type and pericyte-deficient PDGFRβ (platelet-derived growth factor receptor β) heterozygous knockout (
Pdgfrb
+/−
) mice and compared histological changes and neurological functions between the 2 groups. We also examined the effects of conditioned medium harvested from cultured pericytes, or bone marrow-derived macrophages, on the functions of other cell types.

Results:

Localization of PDGFRβ-positive pericytes and F4/80-positive macrophages was temporally and spatially very similar following permanent middle cerebral artery occlusion. Intrainfarct accumulation of macrophages was significantly attenuated in
Pdgfrb
+/−
mice. Intrainfarct pericytes expressed CCL2 (C-C motif ligand 2) and CSF1 (colony stimulating factor 1), both of which were significantly lower in
Pdgfrb
+/−
mice. Cultured pericytes expressed
Ccl2
and
Csf1
, both of which were significantly increased by PDGF-BB and suppressed by a PDGFRβ inhibitor. Pericyte conditioned medium significantly enhanced migration and proliferation of bone marrow-derived macrophages. Poststroke clearance of myelin debris was significantly attenuated in
Pdgfrb
+/−
mice. Pericyte conditioned medium promoted phagocytic activity in bone marrow-derived macrophages, also enhancing both STAT3 (signal transducer and activator of transcription 3) phosphorylation and expression of scavenger receptors,
Msr1
and
Lrp1
. Macrophages processing myelin debris produced trophic factors, enhancing PDGFRβ signaling in pericytes leading to the production of ECM (extracellular matrix) proteins and oligodendrogenesis. Functional recovery was significantly attenuated in
Pdgfrb
+/−
mice, parallel with the extent of tissue repair.

Conclusions:
A reciprocal interaction between pericytes and macrophages is important for poststroke tissue repair and functional recovery.
Inhibition of EZH2 (Enhancer of Zeste Homolog 2) Attenuates Neuroinflammation via H3k27me3/SOCS3/TRAF6/NF-κB (Trimethylation of Histone 3 Lysine 27/Suppressor of Cytokine Signaling 3/Tumor Necrosis Factor Receptor Family 6/Nuclear Factor-κB) in a Rat Model of Subarachnoid Hemorrhage
Authors: Luo Yujie , Fang Yuanjian , Kang Ruiqing , Lenahan Cameron , Gamdzyk Marcin , Zhang Zeyu , Okada Takeshi , Tang Jiping , Chen Sheng , Zhang John H. 
Published: September 2020

Background and Purpose:
Neuroinflammation has been proven to play an important role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). EZH2 (enhancer of zeste homolog 2)-mediated H3K27Me3 (trimethylation of histone 3 lysine 27) has been recognized to play a critical role in multiple inflammatory diseases. However, there is still a lack of evidence to address the effect of EZH2 on the immune response of SAH. Therefore, the aim of this study was to determine the role of EZH2 in SAH-induced neuroinflammation and explore the effect of EZH2 inhibition with its specific inhibitor EPZ6438.

Methods:
The endovascular perforation method was performed on rats to induce subarachnoid hemorrhage. EPZ6438, a specific EZH2 inhibitor, was administered intraperitoneally at 1 hour after SAH. SOCS3 (Suppressor of cytokine signaling 3) siRNA and H3K27me3 CRISPR were administered intracerebroventricularly at 48 hours before SAH to explore potential mechanisms. The SAH grade, short-term and long-term neurobehavioral tests, immunofluorescence staining, and western blots were performed after SAH.

Results:
The expression of EZH2 and H3K27me3 peaked at 24 hours after SAH. In addition, inhibition of EZH2 with EPZ6438 significantly improved neurological deficits both in short-term and long-term outcome studies. Moreover, EPZ6438 treatment significantly decreased the levels of EZH2, H3K27Me3, pathway-related proteins TRAF6 (TNF [tumor necrosis factor] receptor family 6), NF-κB (nuclear factor-κB) p65, proinflammatory cytokines TNF-α, IL (interleukin)-6, IL-1β, but increased the expression levels of SOCS3 and anti-inflammatory cytokine IL-10. Furthermore, administration of SOCS3 siRNA and H3k27me3-activating CRISPR partly abolished the neuroprotective effect of EPZ6438, which indicated that the neuroprotective effect of EPZ6438 acted, at least partly, through activation of SOCS3.

Conclusions:
In summary, the inhibition of EZH2 by EPZ6438 attenuated neuroinflammation via H3K27me3/SOCS3/TRAF6/NF-κB signaling pathway after SAH in rats. By targeting EZH2, this study may provide an innovative method to ameliorate early brain injury after SAH.
Simulations of Atmospheric Rivers, Their Variability, and Response to Global Warming Using GFDL’s New High-Resolution General Circulation Model
Authors: Zhao Ming 
Published: September 2020

AbstractA 50-km-resolution GFDL AM4 well captures many aspects of observed atmospheric river (AR) characteristics including the probability density functions of AR length, width, length–width ratio, geographical location, and the magnitude and direction of AR mean vertically integrated vapor transport (IVT), with the model typically producing stronger and narrower ARs than the ERA-Interim results. Despite significant regional biases, the model well reproduces the observed spatial distribution of AR frequency and AR variability in response to large-scale circulation patterns such as El Niño–Southern Oscillation (ENSO), the Northern and Southern Hemisphere annular modes (NAM and SAM), and the Pacific–North American (PNA) teleconnection pattern. For global warming scenarios, in contrast to most previous studies that show a large increase in AR length and width and therefore the occurrence frequency of AR conditions at a given location, this study shows only a modest increase in these quantities. However, the model produces a large increase in strong ARs with the frequency of category 3–5 ARs rising by roughly 100%–300% K−1. The global mean AR intensity as well as AR intensity percentiles at most percent ranks increases by 5%–8% K−1, roughly consistent with the Clausius–Clapeyron scaling of water vapor. Finally, the results point out the importance of AR IVT thresholds in quantifying modeled AR response to global warming.