bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of diagnosed diabetes in American Indian and Alaska Native adults, 2006–2017
Authors: Bullock Ann , Sheff Karen , Hora Israel , Burrows Nilka Rios , Benoit Stephen R , Saydah Sharon H , Hardin Carmen Licavoli , Gregg Edward W 
Published: April 2020

IntroductionThe objective of this study was to examine recent trends in diagnosed diabetes prevalence for American Indian and Alaska Native (AI/AN) adults aged 18 years and older in the Indian Health Service (IHS) active clinical population.Research design and methodsData were extracted from the IHS National Data Warehouse for AI/AN adults for each fiscal year from 2006 (n=729 470) through 2017 (n=1 034 814). The prevalence of diagnosed diabetes for each year and the annual percentage change were estimated for adults overall, as well as by sex, age group, and geographic region.ResultsAfter increasing significantly from 2006 to 2013, diabetes prevalence for AI/AN adults in the IHS active clinical population decreased significantly from 2013 to 2017. Prevalence was 14.4% (95% CI 13.9% to 15.0%) in 2006; 15.4% (95% CI 14.8% to 16.0%) in 2013; and 14.6% (95% CI 14.1% to 15.2%) in 2017. Trends for men and women were similar to the overall population, as were those for all age groups. For all geographic regions, prevalence either decreased significantly or leveled off in recent years.ConclusionsDiabetes prevalence in AI/AN adults in the IHS active clinical population has decreased significantly since 2013. While these results cannot be generalized to all AI/AN adults in the USA, this study documents the first known decrease in diabetes prevalence for AI/AN people.
The equity impact of a universal child health promotion programme
Authors: Pulkki-Brännström Anni-Maria , Lindkvist Marie , Eurenius Eva , Häggström Jenny , Ivarsson Anneli , Sampaio Filipa , Feldman Inna 
Published: April 2020

BackgroundReal-world evaluations of complex interventions are scarce. We evaluated the effect of the Salut Programme, a universal child health promotion intervention in northern Sweden, on income-related inequalities in positive birth outcomes and healthcare utilisation up to 2 years after delivery.MethodsUsing the mother’s place of residence at delivery, the child and the mother were classified as belonging to either the control area (received care-as-usual) or the intervention area (where the intervention was implemented from 2006) and either the premeasure (children born between 2002 and 2004) or the postmeasure (children born between 2006 and 2008) period. Parents’ earned income was used as the socioeconomic ranking variable. The Relative Concentration Index was computed for six binary birth outcome indicators and for inpatient and day patient care for children and their mothers. Changes in inequality over time were compared using a difference-in-difference approach.ResultsIncome-related inequalities in birth outcomes and child healthcare utilisation were absent, except that full-term pregnancies were concentrated among the poor at premeasure in the intervention area. In contrast, mothers’ healthcare utilisation was significantly pro-poor in the control area. The extent of inequality changed differentially between premeasure and postmeasure for two birth outcomes: full-term pregnancies and infants with normal birth weight. Inequalities in healthcare utilisation did not change significantly in either area over time.ConclusionIn northern Sweden, income-related inequalities in birth outcomes and child healthcare utilisation are largely absent. However, relative inequalities in mothers’ healthcare utilisation are large. We found no evidence that the Salut Programme affected changes in inequality over time.
Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study
Authors: Xie Haibiao , Ma Kaifang , Zhang Jiufeng , Hong Baoan , Zhou Jingcheng , Li Lei , Zhang Kenan , Gong Kan , Cai Lin 
Published: April 2020

BackgroundVon Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome resulting from mutations in the VHL gene lineage, and its prognosis is generally poor. This study aimed to provide a more valuable genotype–phenotype correlation based on the Elongin C binding site in VHL disease.MethodsThis study included 553 patients (194 families) who were diagnosed with VHL disease in our centre from September 2010 to February 2019. According to the type of gene mutation, the patients were divided into the Elongin C binding site missense mutation (EM) group, the non-Elongin C binding site missense mutation (nEM) group and the truncation mutation (TR) group. We analysed and compared the age-related tumour risk and prognosis of the three groups.ResultsA total of 14 new intragenic mutations were found in this cohort. The age-related risk of central nervous system haemangioblastoma (CHB) and pancreatic tumour in the EM group was lower than in the combined nEM-TR group, while the corresponding risk of pheochromocytoma (PHEO) was higher. Additionally, the prognoses of EM and nEM-TR were analysed. The median survival period in the EM group was longer than that in the nEM-TR group, and both the total survival and the CHB-specific survival of the EM group were better than those of the nEM-TR group.ConclusionIn conclusion, our study demonstrated that the EM was an independent risk factor for PHEO. The EM is also an independent protective factor for CHB age-related risk, overall survival and CHB-specific survival in VHL disease. This modified genotype–phenotype correlation integrates gene mutation, the Elongin B binding site, and phenotypic diversity and provides a reference for clinical diagnosis.
Gravitational waves with orbital angular momentum
Authors: Baral Pratyusava , Ray Anarya , Koley Ratna , Majumdar Parthasarathi 
Published: April 2020

AbstractCompact orbiting binaries like the black hole binary system observed in GW150914 carry large amount of orbital angular momentum. The post-ringdown compact object formed after merger of such a binary configuration has only spin angular momentum, and this results in a large orbital angular momentum excess. One significant possibility is that the gravitational waves generated by the system carry away this excess orbital angular momentum. An estimate of this excess is made. Arguing that plane gravitational waves cannot possibly carry any orbital angular momentum, a case is made in this paper for gravitational wave beams carrying orbital angular momentum, akin to optical beams. Restricting to certain specific beam-configurations, we predict that such beams may produce a new type of strain, in addition to the longitudinal strains measured at aLIGO for GW150914 and GW170817. Current constraints on post-ringdown spins, derived within the plane-wave approximation of gravitational waves, therefore stand to improve. The minimal modification that might be needed on a laser-interferometer detector (like aLIGO or VIRGO) to detect such additional strains is also briefly discussed.
Spatiotemporal Regulation of ΔNp63 by TGFβ-Regulated miRNAs Is Essential for Cancer Metastasis
Authors: Bui Ngoc H.B. , Napoli Marco , Davis Andrew John , Abbas Hussein A. , Rajapakshe Kimal , Coarfa Cristian , Flores Elsa R. 
Published: April 2020

Abstract

ΔNp63 is a transcription factor of the p53 family and has crucial functions in normal development and disease. The expression pattern of ΔNp63 in human cancer suggests dynamic regulation of this isoform during cancer progression and metastasis. Many primary and metastatic tumors express high levels of ΔNp63, while ΔNp63 loss is crucial for tumor dissemination, indicating an oscillatory expression of ΔNp63 during cancer progression. Here, we use genetically engineered orthotopic mouse models of breast cancer to show that while depletion of ΔNp63 inhibits primary mammary adenocarcinoma development, oscillatory expression of ΔNp63 in established tumors is crucial for metastatic dissemination in breast cancer. A TGFβ-regulated miRNA network acted as upstream regulators of this oscillatory expression of ΔNp63 during cancer progression. This work sheds light on the pleiotropic roles of ΔNp63 in cancer and unveils critical functions of TGFβ in the metastatic process.

Significance:
This study unveils TGFβ signaling and a network of four miRNAs as upstream regulators of ΔNp63, providing key information for the development of therapeutic strategies to treat cancers that commonly overexpress ΔNp63.
Blocking Angiopoietin-2 Promotes Vascular Damage and Growth Inhibition in Mouse Tumors Treated with Small Doses of Radiation
Authors: Kallio Pauliina , Jokinen Elina , Högström Jenny , Das Suvendu , Heino Sarika , Lähde Marianne , Brodkin Jefim , Korhonen Emilia A. , Alitalo Kari 
Published: April 2020

Abstract

Abnormal vasculature in tumors leads to poor tissue perfusion and cytostatic drug delivery. Although drugs inducing vascular normalization, for example, angiopoietin-2 (Ang2)-blocking antibodies, have shown promising results in preclinical tumor models, clinical studies have so far shown only little efficacy. Because Ang2 is known to play a protective role in stressed endothelial cells, we tested here whether Ang2 blocking could enhance radiation-induced tumor vascular damage. Tumor-bearing mice were treated with anti-Ang2 antibodies every 3 or 4 days starting 3 days before 3 × 2 Gy or 4 × 0.5 Gy whole-body or tumor-focused radiation. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal tumors. Single-cell RNA-sequencing revealed that Ang2 blocking rescued radiation-induced decreases in T cells and cells of the monocyte/macrophage lineage. In addition, anti-Ang2 enhanced radiation-induced apoptosis in cultured endothelial cells. In vivo, combination treatment decreased tumor vasculature and increased tumor necrosis in comparison with tumors treated with monotherapies. These results suggest that a combination of Ang2-blocking antibodies with radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice.

Significance:
These findings offer a preclinical rationale for further testing of the use of radiation in combination with Ang2-blocking antibodies to improve the overall outcome of cancer treatment.
Ablation at Right Coronary Cusp as an Alternative and Favorable Approach to Eliminate Premature Ventricular Complexes Originating From the Proximal Left Anterior Fascicle
Authors: Chen Songwen , Lu Xiaofeng , Peng Shi , Xue Yumei , Zhou Genqing , Ling Zhiyu , Wei Yong , Yang Keping , Fu Wenjun , Cai Lidong , Xu Juan , Ouyang Feifan , Liu Shaowen 
Published: April 2020

Background:
Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC’s characteristics.

Methods:
Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC.

Results:

The earliest activation site (EAS), with Purkinje potential during both PVC and sinus rhythm, was localized at proximal LAF in 8 patients (proximal group) and at nonproximal LAF in 12 patients (nonproximal group). The Purkinje potential preceding PVC-QRS at the EAS in proximal group (32.6±2.5 ms) was significantly earlier than that in nonproximal group (28.3±4.5 ms,
P
=0.025). Similar difference in the Purkinje potentials preceding sinus rhythm QRS at the EAS was also observed between proximal and nonproximal groups (35.1±4.7 versus 25.2±5.0 ms,
P
<0.001). In proximal group, the distance between the EAS to left His bundle and to RCC was shorter than that of nonproximal group (12.3±2.8 versus 19.7±5.0 mm,
P
=0.002, and 3.9±0.8 versus 15.7±7.8 mm,
P
<0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the 2 groups. PVCs were successfully eliminated from RCC for all proximal groups but at left ventricular EAS for nonproximal groups. The radiofrequency application times, ablation time, and procedure time of nonproximal group were longer than that of proximal group. Electrocardiographic analysis showed that, when compared with nonproximal group, the PVCs of proximal group had narrower QRS duration; smaller S wave in leads I, V
5
, and V
6
; lower R wave in leads I, aVR, aVL, V
1
, V
2
, and V
4
; and smaller q wave in leads III and aVF. The QRS duration difference (PVC-QRS and sinus rhythm QRS) <15 ms predicted the proximal LAF origin with high sensitivity and specificity.

Conclusions:
PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.
Irrigated Microwave Catheter Ablation Can Create Deep Ventricular Lesions Through Epicardial Fat With Relative Sparing of Adjacent Coronary Arteries
Authors: Qian Pierre C. , Barry Michael A. , Tran Vu T. , Lu Juntang , McEwan Alistair , Thiagalingam Aravinda , Thomas Stuart P. 
Published: April 2020

Background:
Radiofrequency ablation depth can be inadequate to reach intramural or epicardial substrate, and energy delivery in the pericardium is limited by penetration through epicardial fat and coronary anatomy. We hypothesized that open irrigated microwave catheter ablation can create deep myocardial lesions endocardially and epicardially though fat while acutely sparing nearby the coronary arteries.

Methods:
In-house designed and constructed irrigated microwave catheters were tested in in vitro phantom models and in 15 sheep. Endocardial ablations were performed at 140 to 180 W for 4 minutes; epicardial ablations via subxiphoid access were performed at 90 to 100 W for 4 minutes at sites near coronary arteries.

Results:
Epicardial ablations at 90 to 100 W produced mean lesion depth of 10±4 mm, width 18±10 mm, and length 29±8 mm through median epicardial fat thickness of 1.2 mm. Endocardial ablations at 180 W reached depths of 10.7±3.3 mm, width of 16.6±5 mm, and length of 20±5 mm. Acute coronary occlusion or spasm was not observed at a median separation distance of 2.7 mm (IQR, 1.2–3.4 mm). Saline electrodes recorded unipolar and bipolar electrograms; microwave ablation caused reductions in voltage and changes in electrogram morphology with loss of pace-capture. In vitro models demonstrated the heat sink effect of coronary flow, as well as preferential microwave coupling to myocardium and blood as opposed to lung and epicardial fat phantoms.

Conclusions:
Irrigated microwave catheter ablation may be an effective ablation modality for deep ventricular lesion creation with capacity for fat penetration and sparing of nearby coronary arteries because of cooling endoluminal flow. Clinical translation could improve the treatment of ventricular tachycardia arising from mid myocardial or epicardial substrates.
Validation of Risk Prediction Models to Detect Asymptomatic Carotid Stenosis
Authors: Poorthuis Michiel H. F. , Halliday Alison , Massa M. Sofia , Sherliker Paul , Clack Rachel , Morris Dylan R. , Clarke Robert , de Borst Gert J. , Bulbulia Richard , Lewington Sarah 
Published: April 2020

Background

Significant asymptomatic carotid stenosis (
ACS
) is associated with higher risk of strokes. While the prevalence of moderate and severe
ACS
is low in the general population, prediction models may allow identification of individuals at increased risk, thereby enabling targeted screening. We identified established prediction models for
ACS
and externally validated them in a large screening population.

Methods and Results

Prediction models for prevalent cases with ≥50% ACS were identified in a systematic review (975 studies reviewed and 6 prediction models identified [3 for moderate and 3 for severe
ACS
]) and then validated using data from 596 469 individuals who attended commercial vascular screening clinics in the United States and United Kingdom. We assessed discrimination and calibration. In the validation cohort, 11 178 (1.87%) participants had ≥50% ACS and 2033 (0.34%) had ≥70%
ACS
. The best model included age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, vascular and cerebrovascular disease, measured blood pressure, and blood lipids. The area under the receiver operating characteristic curve for this model was 0.75 (95%
CI,
0.74–0.75) for ≥50%
ACS
and 0.78 (95%
CI,
0.77–0.79) for ≥70%
ACS
. The prevalence of ≥50%
ACS
in the highest decile of risk was 6.51%, and 1.42% for ≥70%
ACS
. Targeted screening of the 10% highest risk identified 35% of cases with ≥50%
ACS
and 42% of cases with ≥70%
ACS
.

Conclusions

Individuals at high risk of significant
ACS
can be selected reliably using a prediction model. The best‐performing prediction models identified over one third of all cases by targeted screening of individuals in the highest decile of risk only.
Generating Global Priority for Addressing Rheumatic Heart Disease: A Qualitative Policy Analysis
Authors: Shawar Yusra Ribhi , Shiffman Jeremy 
Published: April 2020

Background
Rheumatic heart disease (RHD) poses a high burden in low‐income countries, as well as among indigenous and other socioeconomically disadvantaged populations in high‐income countries. Despite its severity and preventability, RHD receives insufficient global attention and resources. We conducted a qualitative policy analysis to investigate the reasons for recent growth but ongoing inadequacy in global priority for addressing RHD.

Methods and Results

Drawing on social science scholarship, we conducted a thematic analysis, triangulating among peer‐reviewed literature, organizational documents, and 20 semistructured interviews with individuals involved in RHD research, clinical practice, and advocacy. The analysis indicates that RHD proponents face 3 linked challenges, all shaped by the nature of the issue. With respect to
leadership and governance
, the fact that RHD affects mostly poor populations in dispersed regions complicates efforts to coordinate activities among RHD proponents and to engage international organizations and donors. With respect to
solution definition
, the dearth of data on aspects of clinical management in low‐income settings, difficulties preventing and addressing the disease, and the fact that RHD intersects with several disease specialties have fueled proponent disagreements about how best to address the disease. With respect to
positioning
, a perception that RHD is largely a problem for low‐income countries and the ambiguity on its status as a noncommunicable disease have complicated efforts to convince policy makers to act.

Conclusions
To augment RHD global priority, proponents will need to establish more effective governance mechanisms to facilitate collective action, manage differences surrounding solutions, and identify positionings that resonate with policy makers and funders.
Phenome‐Wide Analysis of Short‐ and Long‐Run Disease Incidence Following Recurrent Pregnancy Loss Using Data From a 39‐Year Period
Authors: Westergaard David , Nielsen Anna Pors , Mortensen Laust Hvas , Nielsen Henriette Svarre , Brunak Søren 
Published: April 2020

Background

It is unclear how recurrent pregnancy loss (
RPL
) impacts disease risk and whether there is a difference in risk between women with or without a live birth before
RPL
(primary versus secondary
RPL
). We investigated the disease risk following
RPL
, and whether there was a difference between primary and secondary
RPL
.

Methods and Results

Using population‐wide healthcare registries from Denmark, we identified a cohort of 1 370 896 ever‐pregnant women aged 12 to 40 years between 1977 and 2016. Of this cohort, 10 691 (0.77%) fulfilled the criteria for
RPL
(50.0% primary
RPL
). Average follow‐up was 15.8 years. Incidence rate ratios were calculated in a phenome‐wide manner. Diagnoses related to assessment and diagnosis of
RPL
and those appearing later in life were separated using a mixture model. Primary
RPL
increased the risk of subsequent cardiovascular disorders, including atherosclerosis, cerebral infarction, heart failure, and pulmonary embolism, as well as systemic lupus erythematosus, chronic obstructive pulmonary disease, anxiety, and obsessive‐compulsive disorder. Women with secondary
RPL
had no increased risk of cardiovascular disorders. However, we observed an increased risk of gastrointestinal disorders such as irritable bowel syndrome and intestinal malabsorption, as well as mental disorders and obstetric complications.

Conclusions

RPL
is a risk factor for a spectrum of disorders, which is different for primary and secondary
RPL
. Screening following
RPL
explains some associations, but the remaining findings suggest that
RPL
influences or shares cause with cardiovascular disorders, autoimmune disorders, and mental disorders. Research into the pathophysiology of
RPL
and later diseases merits further investigation.
Association Between Walking Pace and Stroke Incidence
Authors: Hayes Sara , Forbes John F. , Celis-Morales Carlos , Anderson Jana , Ferguson Lyn , Gill Jason M.R. , Gray Stuart , Hastie Claire , Iliodromoti Stamatina , Lyall Donald , Pellicori Pierpaolo , Sattar Naveed , Welsh Claire E. , Pell Jill 
Published: April 2020

Background and Purpose—
Stroke incidence in younger and middle-aged people is growing. Despite this, its associations in this subset of the stroke population are unknown, and prevention strategies are not tailored to meet their needs. This study examined the association between self-reported walking pace and incident stroke.

Methods—
Data from the UK Biobank were used in a prospective population-based study. Three hundred and sixty-three thousand, one hundred and thirty-seven participants aged 37 to 73 years (52% women) were recruited. The associations of self-reported walking pace with stroke incidence over follow-up were investigated using Cox proportional-hazard models.

Results—

Among 363,137 participants, 2705 (0.7%) participants developed a fatal or nonfatal stroke event over the mean follow-up period of 6.1 years (interquartile range, 5.4–6.7). Slow walking pace was associated with a higher hazard for stroke incidence (hazard ratio [HR], 1.45 [95% CI, 1.26–1.66];
P
<0.0001). Stroke incidence was not associated with walking pace among people <65 years of age. However, slow walking pace was associated with a higher risk of stroke among participants aged ≥65 years (HR, 1.42 [95% CI, 1.17–1.72];
P
<0.0001). A higher risk for stroke was observed on those with middle (HR, 1.28 [95% CI, 1.01–1.63];
P
=0.039) and higher (HR, 1.29 [95% CI, 1.05–1.69];
P
=0.012) deprivation levels but not in the least deprived individuals. Similarly, overweight (HR, 1.30 [95% CI, 1.04–1.63];
P
=0.019) and obese (HR, 1.33 [95% CI, 1.09–1.63];
P
=0.004) but not normal-weight individuals had a higher risk of stroke incidence.

Conclusions—
Slow walking pace was associated with a higher risk of stroke among participants over 64 years of age in this population-based cohort study. The addition of the measurement of self-reported walking pace to primary care or public health clinical consultations may be a useful screening tool for stroke risk.