bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detrital zircon populations of the eastern Laurentian margin in the Appalachians
Authors: Kuiper Yvette D. , Hepburn J. Christopher 
Published: October 2020

Abstract
Newly compiled U-Pb detrital zircon data from eight geographic domains along the eastern Laurentian margin from Newfoundland (Canada) to Alabama (United States) show a highly consistent signature along strike, with only minor local variations. The Precambrian signature is characterized by a small ca. 2.7 Ga population and a major ca. 1.9–0.9 Ga population that peaks at ca. 1.2–1.0 Ga. Detrital zircon populations are from Laurentian Archean crust (ca. 2.7 Ga population), Paleoproterozoic orogens (ca. 1.9–1.6 Ga), the Granite-Rhyolite Province (ca. 1.5–1.4 Ga), and the Elzevir terrane and Grenville Province (ca. 1.3–0.9 Ga). The Mesoproterozoic populations vary in size depending on proximity to the ca. 1.5–1.4 Ga Granite-Rhyolite Province, the ca. 1245–1225 Ma Elzevir terrane, and the ca. 1.2–0.9 Ga Grenville Province. A middle Ordovician zircon population varies in size along strike depending on input from the Taconic orogenic belt, but it is strongest in the northern Appalachians. Because of the general along-strike consistency in detrital zircon age populations, the compilation of all 7534 concordant U-Pb detrital zircon data can be used in future U-Pb detrital zircon studies as an indicator for eastern Laurentian margin sources.
Childhood morbidity and its determinants: evidence from 31 countries in sub-Saharan Africa
Authors: Adedokun Sulaimon T , Yaya Sanni 
Published: October 2020

BackgroundAlthough under-five mortality reduced globally from 93 per 1000 live births in 1990 to 39 in 2018, sub-Saharan Africa witnessed an increase from 31% in 1990 to 54% in 2018. Morbidity has been reported to contribute largely to these deaths. This study examined the factors that are associated with childhood morbidity in sub-Saharan Africa.MethodsDemographic and Health Surveys of 31 countries in sub-Saharan Africa were used in this study. The study involved 189 069 children who had or did not have fever, cough or diarrhoea in the 2 weeks preceding the surveys. Descriptive statistics and binary logistic regression were applied in the analysis.ResultsAbout 22% of the children suffered from fever, 23% suffered from cough and 16% suffered from diarrhoea. While the odds of experiencing fever increased by 37% and 18%, respectively, for children from poorest and poorer households, children of women aged 15–24 and 25–34 years are 47% and 23%, respectively, more likely to experience diarrhoea. The probability of suffering from morbidity increased for children who are 12–23 months, of higher order birth, small in size at birth and from households with non-improved toilet facility.ConclusionsThis study has shown that childhood morbidity remains a major health challenge in sub-Saharan Africa with socioeconomic, maternal, child’s and environmental factors playing significant roles. Efforts at addressing this problem should consider these factors.
Spatial variations and associated factors of modern contraceptive use in Ethiopia: a spatial and multilevel analysis
Authors: Tegegne Teketo Kassaw , Chojenta Catherine , Forder Peta Michelle , Getachew Theodros , Smith Roger , Loxton Deborah 
Published: October 2020

ObjectiveTo assess spatial variations in modern contraceptive use and to identify factors associated with it among married women in Ethiopia.DesignCross-sectional analysis of population-based and health facility data.SettingEthiopia Demographic and Health Survey data linked to Service Provision Assessment data.Population8473 married women and 1020 facilities that reported providing family planning services.MethodsA linked secondary data analysis of population and health facility data was carried out. Both multilevel and spatial analyses were conducted to identify key determinants of women’s use of modern contraceptive and spatial clustering of modern contraceptive use.Main outcome measureModern contraceptive use.ResultsAbout 24% of the variation in the use of modern contraception was accounted for by location. A one-unit increase in the mean score of health facilities’ readiness to provide short-term modern contraceptives in a typical region was associated with a 20-fold increase in the odds of modern contraceptive use (adjusted OR (AOR) 20.49, 95% CI 1.44 to 29.54). In the spatial analysis, it was found that Addis Ababa and the Amhara region had high clusters of modern contraceptive use rates. On the other hand, low rates of contraceptive use were clustered in the Afar and Somali regions.ConclusionThere were significant variations in the use of modern contraceptives across the different regions of Ethiopia. Therefore, regions with low contraceptive rates and high fertility rates should be targeted for scaling up and tailoring of services to the culture and lifestyles of the population of those regions.
Prevalence and determinants of breast cancer screening in four sub-Saharan African countries: a population-based study
Authors: Ba Djibril M , Ssentongo Paddy , Agbese Edeanya , Yang Yanxu , Cisse Ramata , Diakite Brehima , Traore Cheick Bougadari , Kamate Bakarou , Kassogue Yaya , Dolo Guimogo , Dembele Etienne , Diallo Hama , Maiga Mamoudou 
Published: October 2020

ObjectivesBreast cancer is the most prevalent cancer and the second leading cause of cancer-related deaths among women after cervical cancer in much of sub-Saharan Africa. This study aims to examine the prevalence and sociodemographic–socioeconomic factors associated with breast cancer screening among women of reproductive age in sub-Saharan Africa.DesignA weighted population-based cross-sectional study using Demographic and Health Surveys (DHS) data. We used all available data on breast cancer screening from the DHS for four sub-Saharan African countries (Burkina Faso, Ivory Coast, Kenya and Namibia). Breast cancer screening was the outcome of interest for this study. Multivariable Poisson regression was used to identify independent factors associated with breast cancer screening.SettingFour countries participating in the DHS from 2010 to 2014 with data on breast cancer screening.ParticipantsWomen of reproductive age 15–49 years (N=39 646).ResultsThe overall prevalence of breast cancer screening was only 12.9% during the study period, ranging from 5.2% in Ivory Coast to 23.1% in Namibia. Factors associated with breast cancer screening were secondary/higher education with adjusted prevalence ratio (adjusted PR)=2.33 (95% CI: 2.05 to 2.66) compared with no education; older participants, 35–49 years (adjusted PR=1.73, 95% CI : 1.56 to 1.91) compared with younger participants 15–24 years; health insurance coverage (adjusted PR=1.57, 95% CI: 1.47 to 1.68) compared with those with no health insurance and highest socioeconomic status (adjusted PR=1.33, 95% CI : 1.19 to 1.49) compared with lowest socioeconomic status.ConclusionDespite high breast cancer mortality rates in sub-Saharan Africa, the prevalence of breast cancer screening is substantially low and varies gradually across countries and in relation to factors such as education, age, health insurance coverage and household wealth index level. These results highlight the need for increased efforts to improve the uptake of breast cancer screening in sub-Saharan Africa.
Implementing a triage tool to improve appropriateness of care for children coming to the emergency department in a small hospital in India
Authors: Joshi Neha , Wadhwani Rakhi , Nagpal Jitender , Bhartia Saru 
Published: October 2020

BackgroundIn 2015, senior consultants at Sitaram Bhartia Institute of Science and Research saw several sick children in their outpatient clinics for which they had been seen in the emergency department the previous day. These children seemed to require admission but were sent home. This prompted us to review the paediatric care provided in our emergency department.MethodsA multidisciplinary team was formed to run this improvement initiative. Review of literature suggested that establishing a triage system around a prevalidated triage tool would help us deliver more appropriate care. The South African Triage Scale was selected and adapted.InterventionsWith the aim of delivering appropriate care to at least 50% of children, a series of sequential interventions were tested using the improvement methodology of Plan-Do-Study-Act (PDSA) cycles, an approach recommended by the Institute for Healthcare Improvement. Learnings from the PDSA cycle of the previous intervention helped decide the subsequent change idea. The interventions included training in use of tool, increasing nurse staffing levels, using team huddles as feedback opportunities, introducing nurse reminders, reducing non-productive work, developing local leadership and training a restricted group of locum paediatricians. Qualitative and quantitative information was analysed to retain or reject change ideas.ResultsAt baseline only 16%–17% of children were receiving appropriate care. The sequential changes resulted in a gradual improvement to a median of 63% of children receiving appropriate care by the end of 20 months.ConclusionsWe succeeded in establishing a paediatric emergency triage system and culture in the given setting through a unique enriching experience. We worked on removing systemic barriers and facilitating change while facing several unexpected outcomes. A sustained iterative approach may be the best way to achieving significant improvement in difficult settings like ours.
Physical activity and sedentary time in a rural adult population in Malawi compared with an age-matched US urban population
Authors: Pratt Michael , Sallis James F , Cain Kelli L , Conway Terry L , Palacios-Lopez Amparo , Zezza Alberto , Spoon Chad , Geremia Carrie M , Gaddis Isis , Amankwah Akuffo , Friedman Jed , Kilic Talip 
Published: October 2020

ObjectivesThis study was designed to assess patterns of objectively measured physical activity (PA) and sedentary behaviour in a sample of adults in a rural setting from a low-income Sub-Saharan African country (Malawi). The patterns of PA and sedentary behaviour in Malawi were compared with US data collected and analysed using the same methodology.MethodsThe Malawi PA data were collected as part of a survey experiment on the measurement of agricultural labor conducted under the World Bank Living Standards Measurement Study program. ActiGraph accelerometers (model GT3X) were worn on the right hip in a household-based sample of 414 working-age adults (15–85 years).ResultsMean total and 95% CIs for PA by category in min/day for Malawi adults were: sedentary 387.6 (377.4–397.8), low-light 222.1 (214.7–229.5), high-light 136.3 (132.7–139.9), moderate 71.6 (68.8–74.5), vigorous 1.1 (0.5–1.8) and moderate-to-vigorous physical activity (MVPA) 72.8 (69.7–75.9). Mean of PA and sedentary behavior (min/day) summed across age and sex groups are compared between Malawi and US samples: sedentary behaviour, 387.6 vs 525.8 (p<0.001); low-light, 222.1 vs 217.0 (p=ns); high-light, 136.3 vs 45.6 (p<0.001); moderate, 71.6 vs 28.0 (p<0.001); vigorous, 1.1 vs 2.5 (p<0.001); MVPA, 72.8 vs 30.5 (p<0.001). Compared with the USA, Malawi participants averaged consistently less sedentary time/day and more minutes/day in all intensity levels of PA, except for low-light and vigorous PA.ConclusionOverall, levels of MVPA and high-light activity in adults in Malawi were substantially higher and sedentary time was substantially lower than those observed in US samples using near identical data collection, scoring and analysis.
Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis
Authors: Lu Liming , Zheng Xiaoyan , Wang Shengwen , Tang Chunzhi , Zhang Yuqing , Yao Gaolei , Zeng Jingchun , Ge Shuqi , Wen Hao , Xu Mingzhu , Guyatt Gordon , Xu Nenggui 
Published: October 2020

Objective
To assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer’s disease.

Methods
The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.

Results

Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI −0.40 to 0.81;
I
2
=99.8%; minimal important difference 3.1–3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: −0.96, 95% CI −0.99 to −0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.

Discussion
From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.

Trial registration number
PROSPERO registration number CRD42019126272.
ATAC-Seq Reveals an
Isl1
Enhancer That Regulates Sinoatrial Node Development and Function
Authors: Galang Giselle , Mandla Ravi , Ruan Hongmei , Jung Catherine , Sinha Tanvi , Stone Nicole R. , Wu Roland S. , Mannion Brandon J. , Allu Prasanna K.R. , Chang Kevin , Rammohan Ashwin , Shi Marie B. , Pennacchio Len A. , Black Brian L. , Vedantham Vasanth 
Published: October 2020

Rationale:

Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the
cis
-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified.

Objective:
To define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function.

Methods and Results:

We used ATAC-seq on sorted neonatal mouse SAN to compare regions of accessible chromatin in PCs and right atrial cardiomyocytes. PC-enriched assay for transposase-accessible chromatin peaks, representing candidate SAN regulatory elements, were located near established SAN genes and were enriched for distinct sets of TF (transcription factor) binding sites. Among several novel SAN enhancers that were experimentally validated using transgenic mice, we identified a 2.9-kb regulatory element at the
Isl1
locus that was active specifically in the cardiac inflow at embryonic day 8.5 and throughout later SAN development and maturation. Deletion of this enhancer from the genome of mice resulted in SAN hypoplasia and sinus arrhythmias. The mouse SAN enhancer also directed reporter activity to the inflow tract in developing zebrafish hearts, demonstrating deep conservation of its upstream regulatory network. Finally, single nucleotide polymorphisms in the human genome that occur near the region syntenic to the mouse enhancer exhibit significant associations with resting heart rate in human populations.

Conclusions:

(1) PCs have distinct regions of accessible chromatin that correlate with their gene expression profile and contain novel SAN enhancers, (2)
cis
-regulation of
Isl1
specifically in the SAN depends upon a conserved SAN enhancer that regulates PC development and SAN function, and (3) a corresponding human
ISL1
enhancer may regulate human SAN function.
Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells
Authors: Aherrahrou Redouane , Guo Liang , Nagraj V. Peter , Aguhob Aaron , Hinkle Jameson , Chen Lisa , Yuhl Soh Joon , Lue Dillon , Alencar Gabriel F. , Boltjes Arjan , van der Laan Sander W. , Farber Emily , Fuller Daniela , Anane-Wae Rita , Akingbesote Ngozi , Manichaikul Ani W. , Ma Lijiang , Kaikkonen Minna U. , Björkegren Johan L.M. , Önengüt-Gümüşcü Suna , Pasterkamp Gerard , Miller Clint L. , Owens Gary K. , Finn Aloke , Navab Mohamad , Fogelman Alan M. , Berliner Judith A. , Civelek Mete 
Published: October 2020

Rationale:
Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes.

Objective:
To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs.

Methods and Results:

We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors
MIA3
. The G allele of the lead risk single nucleotide polymorphism (SNP) rs67180937 was associated with lower VSMC
MIA3
expression and lower proliferation. Lentivirus-mediated silencing of MIA3 (melanoma inhibitory activity protein 3) in VSMCs resulted in lower proliferation, consistent with human genetics findings. Furthermore, we observed a significant reduction of MIA3 protein in VSMCs in thin fibrous caps of late-stage atherosclerotic plaques compared to early fibroatheroma with thick and protective fibrous caps in mice and humans.

Conclusions:

Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high
MIA3
expression may promote atheroprotective VSMC phenotypic transitions, including increased proliferation, which is essential in the formation or maintenance of a protective fibrous cap.
Association Between Adherence to Quality Indicators and 7-Day In-Hospital Mortality After Acute Ischemic Stroke
Authors: Haas Kirsten , Rücker Viktoria , Hermanek Peter , Misselwitz Björn , Berger Klaus , Seidel Günter , Janssen Alfred , Rode Susanne , Burmeister Christoph , Matthis Christine , Koennecke Hans-Christian , Heuschmann Peter U. ,   on behalf of the German Stroke Register Study Group (ADSR)
Published: October 2020

Background and Purpose:
Quality indicators (QI) are an accepted tool to measure performance of hospitals in routine care. We investigated the association between quality of acute stroke care defined by overall adherence to evidence-based QI and early outcome in German acute care hospitals.

Methods:
Patients with ischemic stroke admitted to one of the hospitals cooperating within the ADSR (German Stroke Register Study Group) were analyzed. The ADSR is a voluntary network of 9 regional stroke registers monitoring quality of acute stroke care across 736 hospitals in Germany. Quality of stroke care was defined by adherence to 11 evidence-based indicators of early processes of stroke care. The correlation between overall adherence to QI with outcome was investigated by assessing the association between 7-day in-hospital mortality with the proportion of QI fulfilled from the total number of QI the individual patient was eligible for. Generalized linear mixed model analysis was performed adjusted for the variables age, sex, National Institutes of Health Stroke Scale and living will and as random effect for the variable hospital.

Results:

Between 2015 and 2016, 388 012 patients with ischemic stroke were reported (median age 76 years, 52.4% male). Adherence to distinct QI ranged between 41.0% (thrombolysis in eligible patients) and 95.2% (early physiotherapy). Seven-day in-hospital mortality was 3.4%. The overall proportion of QI fulfilled was median 90% (interquartile range, 75%–100%). In multivariable analysis, a linear association between overall adherence to QI and 7-day in-hospital-mortality was observed (odds ratio adherence <50% versus 100%, 12.7 [95% CI, 11.8–13.7];
P
<0.001).

Conclusions:
Higher quality of care measured by adherence to a set of evidence-based process QI for the early phase of stroke treatment was associated with lower in-hospital mortality.
Gastrointestinal Disorders and Risk of First-Ever Ischemic Stroke
Authors: Roth William H. , Cai Anna , Zhang Cenai , Chen Monica L. , Merkler Alexander E. , Kamel Hooman 
Published: October 2020

Background and Purpose:
Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke.

Methods:
We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors.

Results:
Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15–1.19]) and functional (1.16 [95% CI, 1.15–1.17]), inflammatory (1.13 [95% CI, 1.12–1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12–1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94–1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94–1.00]).

Conclusions:
In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.