bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of big-5 personality traits with cognitive impairment and dementia: a longitudinal study
Authors: Singh-Manoux A , Yerramalla M S , Sabia S , Kivimäki Mika , Fayosse A , Dugravot A , Dumurgier J 
Published: April 2020

BackgroundPersonality traits have been liked to cognitive outcomes such as dementia, but whether these associations are robust to the effects of third variables remains the subject of debate. We examined the role of socioeconomic status, depression (history and depressive symptoms), health behaviours and chronic conditions in the association of the big-5 personality traits with cognitive performance, cognitive impairment and incidence of dementia.MethodsData on 6135 persons (30% women), aged 60–83 years in 2012/13, are drawn from the Whitehall II Study. Participants responded to the 26-item Midlife Development Inventory to assess personality traits (openness, conscientiousness, extraversion, agreeableness and neuroticism), underwent cognitive testing in 2012/13 and 2015/16 and were followed for incidence of dementia (N=231) until 2019.ResultsLogistic regression, adjusted for sociodemographic factors, suggested a cross-sectional association with cognitive impairment for four of the five traits but only neuroticism was associated with incident cognitive impairment. All associations were completely attenuated when the analyses were adjusted for depression. Cox regression (mean follow-up: 6.18 years) adjusted for sociodemographic variables showed higher conscientiousness (HR per SD increment=0.72; 95% CI 0.65 to 0.81) and extraversion (HR=0.85; 95% CI 0.75 to 0.97) to be associated with lower dementia risk; higher neuroticism (HR=1.32; 95% CI 1.17 to 1.49) was associated with increased risk. Further adjustment for depression led to only conscientiousness retaining an association with dementia (HR=0.81; 95% CI 0.69 to 0.96), which was robust to adjustment for all covariates (HR=0.84; 95% CI 0.71 to 0.91; P=0.001).ConclusionOur results show that only conscientiousness has an association with incidence of dementia that is not attributable to socioeconomic status or depression. The association of neuroticism with dementia was explained by depression.
Cultural participation and all-cause mortality, with possible gender differences: an 8-year follow-up in the HUNT Study, Norway
Authors: Løkken B I , Merom D , Sund E R , Krokstad S , Rangul V 
Published: April 2020

BackgroundCultural activities can promote health and longevity, but longitudinal studies examining a broad spectrum of participation are scarce. This study investigated the gender-specific association between all-causes of mortality and participation in single types of cultural activities, amount and participation frequency.MethodsWe used cohort data from the Nord-Trøndelag Health Study (HUNT Study), Norway (2006–2008), resulting in 35 902 participants, aged 20 and above. Cultural participation in receptive and creative activities was measured. HRs were reported for partially and fully adjusted models.ResultsA total of 1905 participants died during the median 8-year follow-up. Mortality risk was higher for non-participants in any receptive or creative activities, except sport event attendees. Gender association was also evaluated: among men, we found similar results as above except for parish work, while women increased their longevity only through creative activity participation. When a number of receptive activities was associated with all-cause mortality, reduced risk occurred with attendance in 2 or 3–4 activities (21% and 31%, respectively). Risk was reduced through creative activities, with participation in 3–5 activities (43%). Gender-specific analyses showed a clear gradient of protective effect in creative activity participation: for men, 28%, 44% and 44% reduction with 1, 2 or 3–5 activities, respectively, and a 28%, 35% and 44% reduction for women.ConclusionFrequently attending at least one cultural activity influenced longevity. Creative activities lowered mortality in both genders, while receptive activity benefits were mostly found for men. Thus, promoting and facilitating engaged cultural lifestyles are vital for longevity.
Do men avoid seeking medical advice? A register-based analysis of gender-specific changes in primary healthcare use after first hospitalisation at ages 60+ in Denmark
Authors: Höhn Andreas , Gampe Jutta , Lindahl-Jacobsen Rune , Christensen Kaare , Oksuyzan Anna 
Published: April 2020

BackgroundIt remains unclear whether women’s greater primary healthcare use reflects a lower treatment-seeking threshold or a health disadvantage. We address this question by studying primary healthcare use surrounding a major health shock.MethodsThis cohort study utilises routinely-collected healthcare data covering the Danish population aged 60+ years between 1996 and 2011. Using a hurdle model, we investigate levels of non-use and levels of primary healthcare use before and after first inpatient hospitalisation for stroke, myocardial infarction (MI), chronic obstructive pulmonary disease (COPD) and gastrointestinal cancers (GIC).ResultsBefore hospitalisation, irrespective of cause, men were more likely than women to be non-users of primary healthcare (OR (95% CI): stroke 1.802 (1.731 to 1.872); MI 1.841 (1.760 to 1.922); COPD 2.160 (2.028 to 2.292); GIC 1.609 (1.525 to 1.693)). Men who were users had fewer primary healthcare contacts than women (proportional change (eβ) (95% CI): stroke 0.821 (0.806 to 0.836); MI 0.796 (0.778 to 0.814); COPD 0.855 (0.832 to 0.878); GIC 0.859 (0.838 to 0.881)). Following hospitalisation, changes in the probability of being a non-user (OR (95% CI): stroke 0.965 (0.879 to 1.052); MI 0.894 (0.789 to 0.999); COPD 0.755 (0.609 to 0.900); GIC 0.895 (0.801 to 0.988)) and levels of primary healthcare use (eβ(95% CI): stroke 1.113 (1.102 to 1.124); MI 1.112 (1.099 to 1.124); COPD 1.078 (1.063 to 1.093); GIC 1.097 (1.079 to 1.114)) were more pronounced among men. Gender differences widened after accounting for survival following hospitalisation.ConclusionWomen’s consistently higher levels of primary healthcare use are likely to be explained by a combination of a lower treatment-seeking threshold and a health disadvantage resulting from better survival in bad health.
C reactive protein impairs adaptive immunity in immune cells of patients with melanoma
Authors: Yoshida Tatsuya , Ichikawa Junya , Giuroiu Iulia , Laino Andressa S , Hao Yuhan , Krogsgaard Michelle , Vassallo Melinda , Woods David M , Stephen Hodi F , Weber Jeffrey 
Published: April 2020

BackgroundHigh C reactive protein (CRP) levels have been reported to be associated with a poor clinical outcome in a number of malignancies and with programmed cell death protein 1 immune checkpoint blockade in patients with advanced cancer. Little is known about the direct effects of CRP on adaptive immunity in cancer. Therefore, we investigated how CRP impacted the function of T cells and dendritic cells (DCs) from patients with melanoma.MethodsThe effects of CRP on proliferation, function, gene expression and phenotype of patient T cells and DCs, and expansion of MART-1 antigen-specific T cells were analyzed by multicolor flow cytometry and RNA-seq. Additionally, serum CRP levels at baseline from patients with metastatic melanoma treated on the Checkmate-064 clinical trial were assessed by a Luminex assay.ResultsIn vitro, CRP inhibited proliferation, activation-associated phenotypes and the effector function of activated CD4+ and CD8+ T cells from patients with melanoma. CRP-treated T cells expressed high levels of interleukin-1β, which is known to enhance CRP production from the liver. CRP also suppressed formation of the immune synapse and inhibited early events in T-cell receptor engagement. In addition, CRP downregulated the expression of costimulatory molecules on mature DCs and suppressed expansion of MART-1-specific CD8+ T cells in a dose-dependent manner by impacting on both T cells and antigen-presenting cells. High-serum CRP levels at baseline were significantly associated with a shorter survival in both nivolumab-treated and ipilimumab-treated patients.ConclusionsThese findings suggest that high levels of CRP induce an immunosuppressivemilieuin melanoma and support the blockade of CRP as a therapeutic strategy to enhance immune checkpoint therapies in cancer.Trial registration numberNCT01783938andNCT02983006.
Viral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinoma
Authors: Ho Won Jin , Danilova Ludmila , Lim Su Jin , Verma Rohan , Xavier Stephanie , Leatherman James M , Sztein Marcelo B , Fertig Elana J , Wang Hao , Jaffee Elizabeth , Yarchoan Mark 
Published: April 2020

Background and aimsImmune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in hepatocellular carcinoma (HCC), but only a subset of patients respond to these therapies, highlighting a need for novel biomarkers to improve clinical benefit. HCC usually occurs in the setting of liver cirrhosis from chronic hepatitis B or C viral infection, but the effects of viral status on the tumor immune microenvironment and clinical responses to ICIs in HCC remains unclear.MethodsWe conducted a meta-analysis to estimate the objective response rates for PD-1/PD-L1 inhibitors in virally-infected and uninfected patients, and examined the effects of viral etiology on the tumor microenvironment using data from The Cancer Genome Atlas, as well as peripheral blood responses using an independent cohort of patients studied by mass cytometry (cytometry by time-of-flight (CyTOF)).ResultsMeta-analysis comparing objective response rates (ORR) between virally-infected and uninfected patients showed no clinically meaningful difference (absolute difference of ORR in virally-infected vs uninfected=−1.4%, 95% CI: −13.5% to 10.6%). There was no relationship between viral etiology on features of the tumor immune microenvironment that are known to modulate responses to PD-1/PD-L1 inhibitors, and the tumor mutational burden was similar between virally-infected and uninfected HCC. RNA sequencing of tissue-resident T cell and B cell repertoires similarly showed no effect of viral status on their diversity. CyTOF analysis of peripheral blood specimens further demonstrated similar expression of immune-related markers in response to PD-1 inhibitor therapy in virally-infected and uninfected HCC.ConclusionThere is no significant effect of viral etiology on the tumor immune microenvironment in HCC, and viral status should not be used as a criterion to select patients for PD-1/PD-L1 therapy.
The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones
Authors: Poschke Isabel C. , Hassel Jessica C. , Rodriguez-Ehrenfried Aaron , Lindner Katharina A.M. , Heras-Murillo Ignacio , Appel Lena M. , Lehmann Johanna , Lövgren Tanja , Wickström Stina L. , Lauenstein Claudia , Roth Jasmin , König Anna-Katharina , Haanen John B.A.G. , van den Berg Joost , Kiessling Rolf , Bergmann Frank , Flossdorf Michael , Strobel Oliver , Offringa Rienk 
Published: April 2020

Abstract

Purpose:
During our efforts to develop tumor-infiltrating lymphocyte (TIL) therapy to counter the devastating recurrence rate in patients with primary resectable pancreatic ductal adenocarcinoma (PDA), we found that PDA TILs can readily be expanded in vitro and that the majority of resulting TIL cultures show reactivity against the autologous tumor. However, the fraction of tumor-reactive T cells is low. We investigated to which extent this was related to the in vitro expansion.

Experimental Design:
We compared the clonal composition of TIL preparations before and after in vitro expansion using T-cell receptor (TCR) deep sequencing. Our findings for PDA were benchmarked to experiments with melanoma TILs.

Results:
We found that the TIL TCR repertoire changes dramatically during in vitro expansion, leading to loss of tumor- dominant T-cell clones and overgrowth by newly emerging T-cell clones that are barely detectable in the tumor. These changes are primarily driven by differences in the intrinsic in vitro expansion capacity of T-cell clones. Single-cell experiments showed an association between poor proliferative capacity and expression of markers related to antigen experience and dysfunction. Furthermore, we found that spatial heterogeneity of the TIL repertoire resulted in TCR repertoires that are greatly divergent between TIL cultures derived from distant tumor samples of the same patient.

Conclusions:
Culture-induced changes in clonal composition are likely to affect tumor reactivity of TIL preparations. TCR deep sequencing provides important insights into the factors that govern the outcome of in vitro TIL expansion and thereby a path toward optimization of the production of TIL preparations with high therapeutic efficacy.
See related commentary by Lozano-Rabella and Gros, p. 4177
Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer
Authors: Kim Richard D. , Azad Nilofer S. , Morse Michael A. , Poplin Elizabeth , Mahipal Amit , Tan Benjamin , Mavroukakis Sharon A. , Fantini Massimo , Tsang Kwong Y. , Zaki Anjum , Torrealba Jose , Arlen Philip M. , Beg Muhammad S. 
Published: April 2020

Abstract

Purpose:
Patients with metastatic colorectal cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer.

Patients and Methods:
Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required on the basis of the assumption that ensituximab would improve median overall survival (OS) by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients.

Results:
Sixty-three patients with advanced, refractory colorectal cancer were enrolled and 53 subjects were treated in phase II arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment-related adverse events (AE) at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%), and diarrhea (6%). Serious AEs at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin, and hypoxia. No patients discontinued treatment due to drug-related AEs.

Conclusions:
Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer.
As teorias da integração regional
Authors: Silva Armstrong Pereira da 
Published: April 2020

Este texto é uma resenha do livro “Las teorías de la Integración regional: más allá del eurocentrismo” escrito por Briceño Ruiz e publicado em 2018 pelo “Centro de Pensamiento Global”. O livro representa o coroamento da evolução das ideias desse autor, em que ele não só valoriza as práxis e as teorias do Sul Global, como também expressa a sua crítica às interpretações e aplicações acríticas da teoria europeia no entendimento de outras iniciativas de integração regional nos levando a crer que esta obra represente um ponto de interseção entre a disciplina de Regionalismo Internacional e o movimento vanguardista decolonial que também questiona o eurocentrismo a partir da Geopolítica do Conhecimento e Colonização do Saber.
Indústria cultural, ditadura e outras mumunhas mais
Authors: Tomaz Matheus Araujo 
Published: April 2020

O presente artigo busca analisar como as questões ligadas ao desenvolvimento das forças produtivas em “Baby” (1968) de Caetano Veloso e “Roda Viva” (1967) de Chico Buarque foram formalizadas. Para isso, foram utilizados os escritos de Adorno e Horkheimer sobre a indústria cultural e de Roberto Schwarz sobre seus desdobramentos no Brasil como ponto de partida.
Epidemiology and Outcomes of Acute Decompensated Heart Failure in Children
Authors: Lasa Javier J. , Gaies Michael , Bush Lauren , Zhang Wenying , Banerjee Mousumi , Alten Jeffrey A. , Butts Ryan J. , Cabrera Antonio G. , Checchia Paul A. , Elhoff Justin , Lorts Angela , Rossano Joseph W. , Schumacher Kurt , Shekerdemian Lara S. , Price Jack F. ,   for the Pediatric Cardiac Critical Care Consortium (PC)
Published: April 2020

Background:
Acute decompensated heart failure (ADHF) is a highly morbid condition among adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF.

Methods:
Cardiac intensive care unit (CICU) patients ≤18 years of age meeting Pediatric Cardiac Critical Care Consortium criteria for ADHF were included. ADHF was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis, therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality were identified using logistic regression.

Results:

Among 26 294 consecutive admissions (23 centers), 1494 (6%) met criteria for analysis. Median age was 0.93 years (interquartile range, 0.1–9.3 years). Patients with congenital heart disease (CHD) comprised 57% of the cohort. Common therapies included the following: vasoactive infusions (88%), central venous catheters (86%), mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%). Median length of CICU stay was 7.9 days (interquartile range, 3–18 days) and the CICU readmission rate was 22%. Overall, CICU mortality was 15% although higher for patients with CHD versus non-CHD (19% versus 11%;
P
<0.001). Independent risk factors associated with CICU mortality included age <30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary hypertension, extracorporeal membrane oxygenation, and cardiac arrest.

Conclusions:
ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with CHD. Opportunities exist to determine best practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal heart transplantation candidacy to improve outcomes for these patients.
Transcatheter Aortic Valve Replacement Programs: Clinical Outcomes and Developments
Authors: Kumar Vinayak , Sandhu Gurpreet S. , Harper Charles M. , Ting Henry H. , Rihal Charanjit S. 
Published: April 2020

Abstract:
Transcatheter aortic valve replacement is a relatively recent revolutionary treatment that has now become a standard procedure for treating severe aortic stenosis. In this article, the authors review the clinical history of transcatheter aortic valve replacement, summarize the major clinical trials, and describe the evolution of the technique over time. In doing so, the authors hope to provide a clear and concise review of the history and clinical evidence behind transcatheter aortic valve replacement.
Between Old and New in Yemenite Midrashic Literature
Authors: Schlossberg Eliezer 
Published: April 2020

Abstract
The Midrashim mentioned and described briefly in this article—R. Avraham ben Shlomo’s commentary on the early and later prophets, the Midrash Shoʿel U-Meshiv, and the anonymous Midrash on the Torah written at the beginning of the sixteenth century—represent the transitional stage between the classic and the later Yemenite Midrash. The former are written in a mixture of Hebrew and Arabic, based on rabbinic writings and on the teachings of great medieval scholars such as R. Saadia Gaon and Maimonides, while the latter are written almost solely in Hebrew and based mainly on esoteric, symbolic, allegorical, and kabbalistic elements. Those written in the intermediate period between the old and the new combine all these characteristics.
Networked Church
Authors: Roberts Richard John 
Published: April 2020

Abstract
This article explores some of the recent deliberations concerning the nature of networked church. According to earlier sociological theory, the usual trajectory for newly formed churches (and religious movements) is that they become denominations, particularly in the context of the transition to second-generation leadership. Recent history suggests that this is not an inevitable trajectory, as many churches founded in the middle of the twentieth century continue to exist in the form of networks. Theological and sociological factors are relevant to the question of whether these churches will eventually become denominations. This article summarizes different attempts to understand the nature of networks and suggests that it is possible to conceptualize a continuum from loose networks to highly centralized ecclesial bodies. This continuum indicates possible transitions from one type of structure to another, but such transitions are not inevitable, and network structures may prove to be enduring.
Albert B. Norton and the Mukti Revival
Authors: Danielson Robert A. 
Published: April 2020

Abstract
Albert Benjamin Norton (1847–1923) is an obscure but important figure in the history of Pentecostalism in India. As a Holiness faith missionary who arrived in India at the calling of Bishop William Taylor, Norton worked in Central India before returning to the United States. He and his wife returned to India at the request of Pandita Ramabai to help build the Mukti Mission and later the accompanying Dhond home for boys. It was Norton who first introduced the speaking of tongues at the Mukti Mission in The Apostolic Faith in 1907, and he remained a friend of Ramabai’s throughout her life. Norton moved from the holiness position to Pentecostalism but maintained his position as an independent faith-based missionary throughout his ministry. This article demonstrates Norton’s connections to the Holiness Movement through Taylor and the first Free Methodist missionaries and argues for his influence on Ramabai as a partner in mission.
Let’s (Not) (Dis)Agree to Disagree!? Some Thoughts on the ‘Dispute’ Requirement in International Adjudication
Authors: Kulick Andreas 
Published: April 2020

Abstract
International courts and tribunals only enjoy jurisdiction to settle a ‘dispute’. ‘Dispute’ requires disagreement. However, what if the parties disagree over whether there actually exists such disagreement? What if, before the International Court of Justice, the respondent argues that there is no ‘dispute’ because it declined to react to the applicant’s contentions? In other words, can a disputing party avoid a dispute by playing dead? On the other hand, where does one draw the line in order to prevent the applicant from seizing an international court or tribunal where there is in fact no real disagreement between the parties? This article critically assesses the Court’s case law on the ‘dispute’ requirement and argues for a fragmented approach to ‘dispute’ in international adjudication that carefully defines this jurisdictional requirement along the lines of the judicial function of the respective international judicial dispute settlement forum.