bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study
Authors: Wilkinson Chris , Clegg Andrew , Todd Oliver , Rockwood Kenneth , Yadegarfar Mohammad E , Gale Chris P , Hall Marlous 
Published: November 2020

Abstract

Background
Atrial fibrillation (AF) is common in older people and is associated with increased stroke risk that may be reduced by oral anticoagulation (OAC). Frailty also increases with increasing age, yet the extent of OAC prescription in older people according to extent of frailty in people with AF is insufficiently described.

Methods
An electronic health records study of 536,955 patients aged ≥65 years from ResearchOne in England (384 General Practices), over 15.4 months, last follow-up 11th April 2017. OAC prescription for AF with CHA2DS2-Vasc ≥2, adjusted (demographic and treatments) risk of all-cause mortality, and subsequent cerebrovascular disease, bleeding and falls were estimated by electronic frailty index (eFI) category of fit, mild, moderate and severe frailty.

Results
AF prevalence and mean CHA2DS2-Vasc for those with AF increased with increasing eFI category (fit 2.9%, 2.2; mild 11.2%, 3.2; moderate 22.2%, 4.0; and severe 31.5%, 5.0). For AF with CHA2DS2-Vasc ≥2, OAC prescription was higher for mild (53.2%), moderate (55.6%) and severe (53.4%) eFI categories than fit (41.7%). In those with AF and eligible for OAC, frailty was associated with increased risk of death (HR for severe frailty compared with fit 4.09, 95% confidence interval 3.43–4.89), gastrointestinal bleeding (2.17, 1.45–3.25), falls (8.03, 4.60–14.03) and, among women, stroke (3.63, 1.10–12.02).

Conclusion
Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.
Mechanisms of Vascular Remodeling in Hypertension
Authors: Humphrey Jay D 
Published: November 2020

Abstract
Hypertension is both a cause and a consequence of central artery stiffening, which in turn is an initiator and indicator of myriad disease conditions and thus all-cause mortality. Such stiffening results from a remodeling of the arterial wall that is driven by mechanical stimuli and mediated by inflammatory signals, which together lead to differential gene expression and concomitant changes in extracellular matrix composition and organization. This review focuses on biomechanical mechanisms by which central arteries remodel in hypertension within the context of homeostasis—what promotes it, what prevents it. It is suggested that the vasoactive capacity of the wall and inflammatory burden strongly influence the ability of homeostatic mechanisms to adapt the arterial wall to high blood pressure or not. Maladaptation, often reflected by inflammation-driven adventitial fibrosis, not just excessive intimal–medial thickening, significantly diminishes central artery function and disturbs hemodynamics, ultimately compromising end organ perfusion and thus driving the associated morbidity and mortality. It is thus suggested that there is a need for increased attention to controlling both smooth muscle phenotype and inflammation in hypertensive remodeling of central arteries, with future studies of the often adaptive response of medium-sized muscular arteries promising to provide additional guidance.
Trajectories of Alcohol Use and Related Harms for Managed Alcohol Program Participants over 12 Months Compared with Local Controls: A Quasi-Experimental Study
Authors: Stockwell T , Zhao J , Pauly B , Chow C , Vallance K , Wettlaufer A , Saunders J B , Chick J 
Published: November 2020

Abstract

Aim
Investigate changes in alcohol use and related harm using the first multisite, controlled, longitudinal study of Managed Alcohol Programs (MAPs). MAPs provide regular doses of alcohol, accommodation, social supports and healthcare to unstably housed people with alcohol dependence.

Methods
A multisite, quasi-experimental, longitudinal study was conducted in day centres, shelters and residential programs for unstably housed people. There were 59 MAP participants from six Canadian cities and 116 local controls. Self-reported alcohol consumption and harms were assessed at 0-2, 6 and 12 months. Liver function test results were accessed for MAP participants.

Results
Both groups had similar reductions in mean drinks per day (MAP: -8.11; controls: -8.54 controls, P &lt; 0.001) and days drinking per month (MAP: -2.51 days, P &lt; 0.05; control: -4.81 days, P = 0.0001) over 6–-12 months. Both reduced non-beverage alcohol consumption. MAP participants reported significantly fewer harms at both 0-2 and 6 months than controls. MAP participants had similar total consumption to controls, but spread out over more days (25.41 versus 19.64 days per month, P = 0.001). After leaving a MAP, participants’ liver status deteriorated, with increases in both aspartate transaminase and bilirubin levels. MAP sites with effective policies on outside drinking drank less and had fewer harms.

Conclusion
MAP participants drank less hazardously than controls, especially with effective management of non-MAP drinking. Reductions in alcohol use and harms occurred for both groups, although MAP participants reported fewer harms at 0-6 months. Departing an MAP was associated with deterioration in liver status. Although providing stable housing, MAPs did not worsen health or increase alcohol use.
Towards deep phenotyping pregnancy: a systematic review on artificial intelligence and machine learning methods to improve pregnancy outcomes
Authors: Davidson Lena , Boland Mary Regina 
Published: November 2020

Abstract

Objective
Development of novel informatics methods focused on improving pregnancy outcomes remains an active area of research. The purpose of this study is to systematically review the ways that artificial intelligence (AI) and machine learning (ML), including deep learning (DL), methodologies can inform patient care during pregnancy and improve outcomes.

Materials and methods
We searched English articles on EMBASE, PubMed and SCOPUS. Search terms included ML, AI, pregnancy and informatics. We included research articles and book chapters, excluding conference papers, editorials and notes.

Results
We identified 127 distinct studies from our queries that were relevant to our topic and included in the review. We found that supervised learning methods were more popular (n = 69) than unsupervised methods (n = 9). Popular methods included support vector machines (n = 30), artificial neural networks (n = 22), regression analysis (n = 17) and random forests (n = 16). Methods such as DL are beginning to gain traction (n = 13). Common areas within the pregnancy domain where AI and ML methods were used the most include prenatal care (e.g. fetal anomalies, placental functioning) (n = 73); perinatal care, birth and delivery (n = 20); and preterm birth (n = 13). Efforts to translate AI into clinical care include clinical decision support systems (n = 24) and mobile health applications (n = 9).

Conclusions
Overall, we found that ML and AI methods are being employed to optimize pregnancy outcomes, including modern DL methods (n = 13). Future research should focus on less-studied pregnancy domain areas, including postnatal and postpartum care (n = 2). Also, more work on clinical adoption of AI methods and the ethical implications of such adoption is needed.
Parallelized calculation of permutation tests
Authors: Ekvall Markus , Höhle Michael , Käll Lukas 
Published: November 2020

AbstractMotivationPermutation tests offer a straightforward framework to assess the significance of differences in sample statistics. A significant advantage of permutation tests are the relatively few assumptions about the distribution of the test statistic are needed, as they rely on the assumption of exchangeability of the group labels. They have great value, as they allow a sensitivity analysis to determine the extent to which the assumed broad sample distribution of the test statistic applies. However, in this situation, permutation tests are rarely applied because the running time of naïve implementations is too slow and grows exponentially with the sample size. Nevertheless, continued development in the 1980s introduced dynamic programming algorithms that compute exact permutation tests in polynomial time. Albeit this significant running time reduction, the exact test has not yet become one of the predominant statistical tests for medium sample size. Here, we propose a computational parallelization of one such dynamic programming-based permutation test, the Green algorithm, which makes the permutation test more attractive.ResultsParallelization of the Green algorithm was found possible by non-trivial rearrangement of the structure of the algorithm. A speed-up—by orders of magnitude—is achievable by executing the parallelized algorithm on a GPU. We demonstrate that the execution time essentially becomes a non-issue for sample sizes, even as high as hundreds of samples. This improvement makes our method an attractive alternative to, e.g. the widely used asymptotic Mann-Whitney U-test.Availabilityand implementationIn Python 3 code from the GitHub repository https://github.com/statisticalbiotechnology/parallelPermutationTest under an Apache 2.0 license.Supplementary informationSupplementary data are available at Bioinformatics online.
Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition
Authors: Wang Zilong , Jiang Changyu , Yao Hongyu , Chen Ouyang , Rahman Sreya , Gu Yun , Zhao Junli , Huh Yul , Ji Ru-Rong 
Published: November 2020

Abstract
Opioids such as morphine are mainstay treatments for clinical pain conditions. Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Recent progress has advanced our understanding of itch circuits in the spinal cord. However, the mechanisms underlying opioid-induced itch are not fully understood, although an interaction between µ-opioid receptor (MOR) and gastrin-releasing peptide receptor (GRPR) in spinal GRPR-expressing neurons has been implicated. In this study we investigated the cellular mechanisms of intrathecal opioid-induced itch by conditional deletion of MOR-encoding Oprm1 in distinct populations of interneurons and sensory neurons. We found that intrathecal injection of the MOR agonists morphine or DAMGO elicited dose-dependent scratching as well as licking and biting, but this pruritus was totally abolished in mice with a specific Oprm1 deletion in Vgat+ neurons [Oprm1-Vgat (Slc32a1)]. Loss of MOR in somatostatin+ interneurons and TRPV1+ sensory neurons did not affect morphine-induced itch but impaired morphine-induced antinociception. In situ hybridization revealed Oprm1 expression in 30% of inhibitory and 20% of excitatory interneurons in the spinal dorsal horn. Whole-cell recordings from spinal cord slices showed that DAMGO induced outward currents in 9 of 19 Vgat+ interneurons examined. Morphine also inhibited action potentials in Vgat+ interneurons. Furthermore, morphine suppressed evoked inhibitory postsynaptic currents in postsynaptic Vgat− excitatory neurons, suggesting a mechanism of disinhibition by MOR agonists. Notably, morphine-elicited itch was suppressed by intrathecal administration of NPY and abolished by spinal ablation of GRPR+ neurons with intrathecal injection of bombesin-saporin, whereas intrathecal GRP-induced itch response remained intact in mice lacking Oprm1-Vgat. Intrathecal bombesin-saporin treatment reduced the number of GRPR+ neurons by 97% in the lumber spinal cord and 91% in the cervical spinal cord, without changing the number of Oprm1+ neurons. Additionally, chronic itch from DNFB-induced allergic contact dermatitis was decreased by Oprm1-Vgat deletion. Finally, naloxone, but not peripherally restricted naloxone methiodide, inhibited chronic itch in the DNFB model and the CTCL model, indicating a contribution of central MOR signalling to chronic itch. Our findings demonstrate that intrathecal morphine elicits itch via acting on MOR on spinal inhibitory interneurons, leading to disinhibition of the spinal itch circuit. Our data also provide mechanistic insights into the current treatment of chronic itch with opioid receptor antagonist such as naloxone.
Comparative Genomics of Strictly Vertically Transmitted, Feminizing Microsporidia Endosymbionts of Amphipod Crustaceans
Authors: Cormier Alexandre , Chebbi Mohamed Amine , Giraud Isabelle , Wattier Rémi , Teixeira Maria , Gilbert Clément , Rigaud Thierry , Cordaux Richard 
Published: November 2020

AbstractMicrosporidia are obligate intracellular eukaryotic parasites of vertebrates and invertebrates. Microsporidia are usually pathogenic and undergo horizontal transmission or a mix of horizontal and vertical transmission. However, cases of nonpathogenic microsporidia, strictly vertically transmitted from mother to offspring, have been reported in amphipod crustaceans. Some of them further evolved the ability to feminize their nontransmitting male hosts into transmitting females. However, our understanding of the evolution of feminization in microsporidia is hindered by a lack of genomic resources. We report the sequencing and analysis of three strictly vertically transmitted microsporidia species for which feminization induction has been demonstrated (Nosema granulosis) or is strongly suspected (Dictyocoela muelleri and Dictyocoela roeselum), along with a draft genome assembly of their host Gammarus roeselii. Contrary to horizontally transmitted microsporidia that form environmental spores that can be purified, feminizing microsporidia cannot be easily isolated from their host cells. Therefore, we cosequenced symbiont and host genomic DNA and devised a computational strategy to obtain genome assemblies for the different partners. Genomic comparison with feminizing Wolbachia bacterial endosymbionts of isopod crustaceans indicated independent evolution of feminization in microsporidia and Wolbachia at the molecular genetic level. Feminization thus represents a remarkable evolutionary convergence of eukaryotic and prokaryotic microorganisms. Furthermore, a comparative genomics analysis of microsporidia allowed us to identify several candidate genes for feminization, involving functions such as DNA binding and membrane fusion. The genomic resources we generated contribute to establish Gammarus roeselii and its microsporidia symbionts as a new model to study the evolution of symbiont-mediated feminization.
Attitudes of Homebound Older Adults and Their Caregivers Toward Research and Participation as Research Advisors
Authors: Eaton England Ashley L , Ritchie Christine S , Mickler Alexandria , Perissinotto Carla M , Garrigues Sarah K , Leff Bruce , Sheehan Orla C , Harrison Krista L 
Published: November 2020

Abstract

Background and Objectives
Homebound older adults and their caregivers have not historically been engaged as advisors in patient-centered outcomes research. This study aimed to understand the attitudes of homebound older adults and their caregivers toward research and participation as research advisors.

Research Design and Methods
Descriptive thematic analysis of semistructured interviews conducted with 30 homebound older adults and caregivers recruited from home-based medical care practices. Interview questions addressed opinions on research and preferences for engaging as research advisors.

Results
Of 30 participants, 22 were female, 17 were people of color, and 11 had Medicaid. Two themes emerged related to perceptions of research overall: (a) utility of research and (b) relevance of research. Overall, participants reported positive attitudes toward research and felt that research could affect people like them. Three themes emerged related to participating as research advisors: (a) motivators, (b) barriers, and (c) preferences. Participants were open to engaging in a variety of activities as research advisors. Most participants were motivated by helping others. Common barriers included time constraints and caregiving responsibilities, and physical barriers for homebound individuals. Participants also reported fears such as lacking the skills or expertise to contribute as advisors. Many were willing to participate if these barriers were accommodated and shared their communication preferences.

Discussion and Implications
Diverse homebound older adults and caregivers are willing to be engaged as research advisors and provided information to inform future engagement strategies. Findings can inform efforts to meet new age-inclusive requirements of the National Institutes of Health.
Midlife Marital Dissolution and the Onset of Cognitive Impairment
Authors: Brown Susan L , Lin I-Fen , Vielee Alyssa , Mellencamp Kagan A 
Published: November 2020

Abstract

Background and Objectives
Marital dissolution has become more common in midlife with the doubling of the divorce rate among middle-aged adults. Guided by the stress model that stipulates losing economic, social, and psychological resources lowers well-being, we posited that midlife adults who experienced divorce or widowhood were at greater risk of cognitive impairment than the continuously married. Subsequent repartnering was expected to negate the increased risk.

Research Design and Methods
We used data from the 1998–2016 Health and Retirement Study to estimate discrete-time event history models using logistic regression to predict cognitive impairment onset for men and women.

Results
Roughly 27% of men who experienced spousal death in midlife went on to experience mild cognitive impairment by age 65. For women, experiencing divorce or widowhood was associated with higher odds of cognitive impairment onset although these differentials were accounted for by economic, social, and psychological resources. Men and women who repartnered after marital dissolution did not appreciably differ from their continuously married counterparts in terms of their likelihoods of cognitive impairment onset.

Discussion and Implications
A stressful life event, midlife marital dissolution can be detrimental to cognitive well-being, placing individuals at increased risk of developing dementia in later life. The growing diversity of partnership experiences during the second half of life points to the continued importance of examining how union dissolution and formation shape health and well-being.
A scoping review of theories and conceptual frameworks used to analyse health financing policy processes in sub-Saharan Africa
Authors: Jones Catherine M , Gautier Lara , Ridde Valéry 
Published: November 2020

AbstractHealth financing policies are critical policy instruments to achieve Universal Health Coverage, and they constitute a key area in policy analysis literature for the health policy and systems research (HPSR) field. Previous reviews have shown that analyses of policy change in low- and middle-income countries are under-theorised. This study aims to explore which theories and conceptual frameworks have been used in research on policy processes of health financing policy in sub-Saharan Africa and to identify challenges and lessons learned from their use. We conducted a scoping review of literature published in English and French between 2000 and 2017. We analysed 23 papers selected as studies of health financing policies in sub-Saharan African countries using policy process or health policy-related theory or conceptual framework ex ante. Theories and frameworks used alone were from political science (35%), economics (9%) and HPSR field (17%). Thirty-five per cent of authors adopted a ‘do-it-yourself’ (bricolage) approach combining theories and frameworks from within political science or between political science and HPSR. Kingdon’s multiple streams theory (22%), Grindle and Thomas’ arenas of conflict (26%) and Walt and Gilson’s policy triangle (30%) were the most used. Authors select theories for their empirical relevance, methodological rational (e.g. comparison), availability of examples in literature, accessibility and consensus. Authors cite few operational and analytical challenges in using theory. The hybridisation, diversification and expansion of mid-range policy theories and conceptual frameworks used deductively in health financing policy reform research are issues for HPSR to consider. We make three recommendations for researchers in the HPSR field. Future research on health financing policy change processes in sub-Saharan Africa should include reflection on learning and challenges for using policy theories and frameworks in the context of HPSR.
The association between the pattern of change in N-terminal pro-B-type natriuretic peptide and short-term outcomes in children undergoing surgery for congenital heart disease
Authors: Zheng Haiqing , Cui Yanqin , Li Kuanrong , Zhang Jiexin , Qu Jiangbo , Shi Hui , Li LiJuan , Xia Huimin , Chen Xinxin , Liang Huiying 
Published: November 2020

Abstract

OBJECTIVES
This study aimed to determine whether changes in perioperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with short-term outcomes in children undergoing surgery for congenital heart disease (CHD).

METHODS
We retrospectively included 873 consecutive children with CHD after cardiac surgery. NT-proBNP concentrations were collected from each child prior to and at 1, 12, 36 and 72 h after surgery. The patients had postsurgical follow-ups at 30, 90 and 180 days. The end point was postoperative composite adverse events.

RESULTS
The patients were classified into 3 groups using joint latent class mixture time-to-event models: (i) relatively stable (86.7%), (ii) decreasing (7.2%) and (iii) increasing (6.1%). In total, 257 (29.4%) adverse events occurred. The joint latent class mixture time-to-event models showed that increasing NT-proBNP was strongly associated with adverse events, with adjusted hazard ratio of 2.33 (95% confidence interval 1.52–3.60). Multinomial logistic regression showed that the variables associated with the pattern of change were age, weight at surgery, mode of delivery and cardiopulmonary bypass time.

CONCLUSIONS
The pattern of dynamic postsurgical changes in NT-proBNP may facilitate outcome stratification and identification of a high risk for adverse events.
Who Owns What in Macondo? The Flexibilization of the Rules of Evidence in Land Restitution in Colombia
Authors: Ruiz González Luis Enrique , Peña-Huertas Rocío Del Pilar , Parada-Hernández María Mónica , Lozano Valcárcel Alfonso Javier , Triana Ancínez Bryan , Valencia-Herrera Milton Alberto 
Published: November 2020

Abstract
Land restitution programmes, as part of transitional justice systems, make victims face obstacles to prove their material and legal relationship with their dispossessed land. The literature suggests that these obstacles can be overcome by changing the rules of evidence, such as reversing the burden of proof, introducing different legal presumptions and adopting alternative forms of evidence. In Colombia, the Land Restitution Law introduced changes to the rules of evidence for processing land restitution claims. In this article, we claim that this flexibilization of the rules of evidence is essential to guarantee the restitution of property rights to victims, based on a comparison of the evidentiary rules that must be fulfilled by the victims of land dispossession under two transitional justice systems, both of which have been implemented in Colombia in recent years.