bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Biomarkers and Risk of Atrial Fibrillation
Authors: Staerk Laila , Preis Sarah R. , Lin Honghuang , Lubitz Steven A. , Ellinor Patrick T. , Levy Daniel , Benjamin Emelia J. , Trinquart Ludovic 
Published: January 2020

Background:
Identification of protein biomarkers associated with incident atrial fibrillation (AF) may improve the understanding of the pathophysiology, risk prediction, and development of new therapeutics for AF. We examined the associations between 85 protein biomarkers and incident AF.

Methods:
We included participants ≥50 years of age from the FHS (Framingham Heart Study) Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 SD increment of rank-normalized biomarker [hazard ratio]) and 95% CIs for incident AF were calculated using Cox regression models adjusted for age, sex, height, weight, current smoking, systolic blood pressure, diastolic blood pressure, hypertension treatment, diabetes mellitus, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the false discovery rate to account for multiple testing.

Results:
The study sample comprised 3378 participants (54% women) with mean (SD) age of 61.5 (8.4) years. In total, 401 developed AF over a mean follow-up of 12.3±3.8 years. We observed lower hazard of incident AF associated with higher mean levels of IGF1 (insulin-like growth factor 1; hazard ratio per 1 SD increment in protein level, 0.84 [95% CI, 0.76–0.93]), and higher hazard of incident AF associated with higher mean levels of both IGFBP1 (insulin-like growth factor-binding protein 1; hazard ratio, 1.24 [95% CI, 1.1–1.39]) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio, 1.73 [95% CI, 1.52–1.96]).

Conclusions:
Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.
Time Trends in Cardiovascular Disease Mortality Across the BRICS
Authors: Zou Zhiyong , Cini Karly , Dong Bin , Ma Yinghua , Ma Jun , Burgner David P. , Patton George C. 
Published: January 2020

Background:
Brazil, Russia, India, China, and South Africa (BRICS) are emerging economies making up almost half the global population. We analyzed trends in cardiovascular disease (CVD) mortality across the BRICS and associations with age, period, and birth cohort.

Methods:
Mortality estimates were derived from the Global Burden of Disease Study 2017. We used age-period-cohort modeling to estimate cohort and period effects in CVD between 1992 and 2016. Period was defined as survey year, and period effects reflect population-wide exposure at a circumscribed point in time. Cohort effects are defined as differences in risks across birth cohort. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated.

Results:
In 2016, there were 8.4 million CVD deaths across the BRICS. Between 1992 and 2016, the reduction in CVD age-standardized mortality rate in BRICS (−17%) was less than in North America (−39%). Eighty-eight percent of the increased number of all-cause deaths resulted from the increase in CVD deaths. The age-standardized mortality rate from stroke and hypertensive heart disease declined by approximately one-third across the BRICS, whereas ischemic heart disease increased slightly (2%). Brazil had the largest age-standardized mortality rate reductions across all CVD categories, with improvement both over time and in recent birth cohorts. South Africa was the only country where the CVD age-standardized mortality rate increased. Different age-related CVD mortality was seen in those ≥50 years of age in China, ≤40 years of age in Russia, 35 to 60 years of age in India, and ≥55 years of age in South Africa. Improving period and cohort risks for CVD mortality were generally found across countries, except for worsening period effects in India and greater risks for ischemic heart disease in Chinese cohorts born in the 1950s and 1960s.

Conclusions:
Except for Brazil, reductions of CVD mortality across the BRICS have been less than that in North America, such that China, India, and South Africa contribute an increasing proportion of global CVD deaths. Brazil’s example suggests that prevention policies can both reduce the risks for younger birth cohorts and shift the risks for all age groups over time.
Orphan G Protein–Coupled Receptor GPRC5B Controls Smooth Muscle Contractility and Differentiation by Inhibiting Prostacyclin Receptor Signaling
Authors: Carvalho Jorge , Chennupati Ramesh , Li Rui , Günther Stefan , Kaur Harmandeep , Zhao Wencai , Tonack Sarah , Kurz Michael , Mößlein Nadja , Bünemann Moritz , Offermanns Stefan , Wettschureck Nina 
Published: January 2020

Background:
G protein–coupled receptors are important regulators of contractility and differentiation in vascular smooth muscle cells (SMCs), but the specific function of SMC-expressed orphan G protein–coupled receptor class C group 5 member B (GPRC5B) is unclear.

Methods:

We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMCs in vitro and in iSM-
Gprc5b
-KO (tamoxifen-inducible, SMC-specific knockout) mice under conditions of arterial hypertension and atherosclerosis in vivo.

Results:

Mesenteric arteries from SMC-specific
Gprc5b
-KOs showed ex vivo significantly enhanced prostacyclin receptor (IP)–dependent relaxation, whereas responses to other relaxant or contractile factors were normal. In vitro, knockdown of GPRC5B in human aortic SMCs resulted in increased IP-dependent cAMP production and consecutive facilitation of SMC relaxation. In line with this facilitation of IP-mediated relaxation, iSM-
Gprc5b
-KO mice were protected from arterial hypertension, and this protective effect was abrogated by IP antagonists. Mechanistically, we show that knockdown of GPRC5B increased the membrane localization of IP both in vitro and in vivo and that GPRC5B, but not other G protein–coupled receptors, physically interacts with IP. Last, we show that enhanced IP signaling in GPRC5B-deficient SMCs not only facilitates relaxation but also prevents dedifferentiation during atherosclerosis development, resulting in reduced plaque load and increased differentiation of SMCs in the fibrous cap.

Conclusions:
Taken together, our data show that GPRC5B regulates vascular SMC tone and differentiation by negatively regulating IP signaling.
Variation in Ultrasound Diagnostic Thresholds for Carotid Stenosis in the United States
Authors: Columbo Jesse A. , Zwolak Robert M. , Arous Edward J. , Goodney Philip P. , Lilly Michael P. , Welch H. Gilbert 
Published: January 2020

Background:
Individuals with carotid stenosis enter surveillance or are considered for surgery on the basis of disease severity assessed by ultrasound. However, there is variation in the ultrasound diagnostic thresholds used to determine disease severity. Our objective was to describe this variation and its potential impact on patients.

Methods:
To describe the variation in carotid ultrasound diagnostic thresholds, we examined testing protocols from 338 accredited vascular testing centers in the United States. To determine the potential impact of this variation, we applied the range of thresholds to carotid ultrasound parameters from 2 groups: a population-based sample ≥65 years of age in the Cardiovascular Health Study (n=4791), and a cohort of patients who underwent surgery for asymptomatic carotid stenosis in the Vascular Quality Initiative registry (n=28 483).

Results:
Internal carotid artery peak systolic velocity was used by all centers to assess disease severity, with 60 distinct thresholds in use. The peak systolic velocity threshold for moderate (≥50%) stenosis ranged from 110 to 245 cm/s (median, 125; 5th and 95th percentile, 125 and 150), and the threshold for severe (≥70%) stenosis ranged from 175 to 340 cm/s (median, 230; 5th and 95th percentile, 230 and 275). In the population-based sample, the 5th percentile threshold would assign a diagnosis of moderate carotid stenosis to twice as many individuals as the 95th percentile threshold (7.9% versus 3.9%; relative risk, 2.01 [CI, 1.70–2.38]). In the surgical cohort, 1 in 10 (9.8%) patients had peak systolic velocity values that warranted the diagnosis of severe carotid stenosis at centers in the 5th percentile, but not in the 95th.

Conclusions:
The diagnostic threshold for carotid stenosis varies considerably. Whether or not a person is said to have moderate stenosis and enters surveillance, and whether or not they have severe stenosis and are candidates for surgery, can depend on which center performs their ultrasound.
Validation of the CERES Edition-4A Surface-Only Flux Algorithms
Authors: Kratz David P. , Gupta Shashi K. , Wilber Anne C. , Sothcott Victor E. 
Published: January 2020

AbstractSurface radiative fluxes have been derived with the objective of supplementing top-of-atmosphere (TOA) radiative fluxes being measured under NASA’s Clouds and the Earth’s Radiant Energy System (CERES) project. This has been accomplished by using combinations of CERES TOA measurements, parameterized radiative transfer algorithms, and high-quality meteorological datasets available from reanalysis projects. Current CERES footprint-level products include surface fluxes derived from two shortwave (SW) and three longwave (LW) algorithms designated as SW models A and B and LW models A, B, and C. The SW and LW models A work for clear conditions only; the other models work for both clear and cloudy conditions. The current CERES Edition-4A computed surface fluxes from all models are validated against ground-based flux measurements from high-quality surface networks like the Baseline Surface Radiation Network and NOAA’s Surface Radiation Budget Network (SURFRAD). Validation results as systematic and random errors are provided for all models, separately for five different surface types and combined for all surface types as tables and scatterplots. Validation of surface fluxes is now a part of CERES processing and is used to continually improve the above algorithms. Since both models B work for clear and cloudy conditions alike and meet the accuracy requirement, their results are considered to be the most reliable and most likely to be retained for future work. Both models A have limited use given that they work for clear skies only. Models B will continue to undergo further improvement as more validation results become available.
Higher Sea Levels at Hawaii Caused by Strong El Niño and Weak Trade Winds
Authors: Long Xiaoyu , Widlansky Matthew J. , Schloesser Fabian , Thompson Philip R. , Annamalai H. , Merrifield Mark A. , Yoon Hyang 
Published: January 2020

AbstractHawaii experienced record-high sea levels during 2017, which followed the 2015 strong El Niño and coincided with weak trade winds in the tropical northeastern Pacific. The record sea levels were associated with a combination of processes, an important contributing factor of which was the persistent high sea level (~10 cm above normal) over a large region stretching between Hawaii and Mexico. High sea levels at Mexico are known to occur during strong El Niño as the coastal thermocline deepens. Planetary wave theory predicts that these coastal anomalies propagate westward into the basin interior; however, high sea levels at Hawaii do not occur consistently following strong El Niño events. In particular, Hawaii sea levels remained near normal following the previous strong El Niño of 1997. The processes controlling whether Hawaii sea levels rise after El Niño have so far remained unknown. Atmosphere-forced ocean model experiments show that anomalous surface cooling, controlled by variable trade winds, impacts sea level via mixed layer density, explaining much of the difference in Hawaiian sea level response after the two recent strong El Niño events. In climate model projections with greenhouse warming, more frequent weak trade winds following El Niño events are expected, suggesting that the occurrence of high sea levels at Hawaii will increase as oceanic anomalies more often traverse the basin.
Immune dysregulation in patients with RAG deficiency and other forms of combined immune deficiency
Authors: Delmonte Ottavia M. , Villa Anna , Notarangelo Luigi D. 
Published: January 2020

AbstractTraditionally, primary immune deficiencies have been defined based on increased susceptibility to recurrent and/or severe infections. However, immune dysregulation, manifesting with autoimmunity or hyperinflammatory disease, has emerged as a common feature. This is especially true in patients affected by combined immune deficiency (CID), a group of disorders caused by genetic defects that impair, but do not completely abolish, T-cell function. Hypomorphic mutations in the recombination activating genes RAG1 and RAG2 represent the prototype of the broad spectrum of clinical and immunological phenotypes associated with CID. The study of patients with RAG deficiency and with other forms of CID has revealed distinct abnormalities in central and peripheral T- and B-cell tolerance as the key mechanisms involved in immune dysregulation. Understanding the pathophysiology of autoimmunity and hyperinflammation in these disorders may also permit more targeted therapeutic interventions.
Current genetic landscape in common variable immune deficiency
Authors: Abolhassani Hassan , Hammarström Lennart , Cunningham-Rundles Charlotte 
Published: January 2020

AbstractUsing whole-exome sequencing to examine the genetic causes of immune deficiency in 235 common variable immunodeficiency (CVID) patients seen in the United States (Mount Sinai, New York), 128 patients from Sweden, and 208 from Iran revealed 68 known disease-causing genes underlying this heterogeneous immune defect. The patients at the time of study ranged from 4 to 90 years of age. Overall, 31%, 36%, and 54% of the patients in the US, Swedish, or Iranian cohorts had mutations. The multiplicity of genes identified in the 571 subjects reflects the complex requirements of B-cell antigen signaling, activation, survival, migration, maturation, and maintenance of antibody-secreting memory B-cell populations to the plasma cell stage. For the US and Swedish cohorts, CVID subjects with noninfectious complications, lymphoid infiltrations, inflamatory conditions, or autoimmunity were somewhat more likely to have an identifiable gene, but in both cohorts, numerous subjects with these medical conditions had no potential gene that could be assigned. Specific clinical patterns of illnesses were also not linked to any given gene defect as there was considerable overlap in clinical presentations. These observations led to a new perspective on the complexity of the immunologic phenotype found in CVID syndrome.
Screening and treatment of tuberculosis among pregnant women in Stockholm, Sweden, 2016–2017
Authors: Fröberg Gabrielle , Jansson Lena , Nyberg Katherine , Obasi Birgitta , Westling Katarina , Berggren Ingela , Bruchfeld Judith 
Published: January 2020

Swedish National tuberculosis (TB) guidelines recommend screening of active and latent TB (LTBI) among pregnant women (PW) from high-endemic countries or with previous exposure to possibly improve early detection and treatment.We evaluated cascade of care of a newly introduced TB screening programme of pregnant women in Stockholm county in 2016–2017. The algorithm included clinical data and Quantiferon (QFT) at the Maternal Health Care clinics and referral for specialist care upon positive test or TB symptoms.About 29 000 HIV-negative pregnant women were registered yearly, of whom 11% originated from high-endemic countries. In 2016, 72% of these were screened with QFT, of which 22% were QFT positive and 85% were referred for specialist care. In 2017, corresponding figures were 64%, 19% and 96%, respectively. The LTBI treatment rate among all QFT-positive pregnant women increased from 24% to 37% over time. Treatment completion with mainly rifampicin post-partum was 94%. Of the 69 registered HIV-positive pregnant women, 78% originated from high-endemic countries. Of these, 72% where screened with QFT and 15% were positive, but none was treated for LTBI. 9 HIV-negative active pulmonary TB cases were detected (incidence: 215/100 000). None had been screened for TB prior to pregnancy and only one had sought care due to symptoms.Systematic TB screening of pregnant women in Stockholm was feasible with a high yield of unknown LTBI and mostly asymptomatic active TB. Optimised routines improved referrals to specialist care. Treatment completion of LTBI was very high. Our findings justify TB screening of this risk group for early detection and treatment.
Gefapixant in two randomised dose-escalation studies in chronic cough
Authors: Smith Jaclyn A. , Kitt Michael M. , Butera Peter , Smith Steven A. , Li Yuping , Xu Zhi Jin , Holt Kimberley , Sen Shilpi , Sher Mandel R. , Ford Anthony P. 
Published: January 2020

Background and objectivesGefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.Materials and methodsTwo randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50–200 mg, study 2: 7.5–50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.ResultsIn clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.ConclusionsP2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.
Genetic susceptibility to asthma increases the vulnerability to indoor air pollution
Authors: Hüls Anke , Vanker Aneesa , Gray Diane , Koen Nastassja , MacIsaac Julia L. , Lin David T.S. , Ramadori Katia E. , Sly Peter D. , Stein Dan J. , Kobor Michael S. , Zar Heather J. 
Published: January 2020

IntroductionIndoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of exposure to indoor particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM10) and maternal smoking with infant lung function and the role of gene–environment interactions.MethodsData from the Drakenstein Child Health Study, a South African birth cohort, were analysed (n=270). Lung function was measured at 6 weeks and 1 year of age, and lower respiratory tract infection episodes were documented. We measured pre- and postnatal PM10exposures using devices placed in homes, and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores determined from associations with childhood-onset asthma in the UK Biobank were used to investigate effect modifications.ResultsPre- and postnatal exposure to PM10as well as maternal smoking during pregnancy were associated with reduced lung function at 6 weeks and 1 year as well as with lower respiratory tract infection in the first year. Due to a significant interaction between the genetic risk score and prenatal exposure to PM10, infants carrying more asthma-related risk alleles were more susceptible to PM10-associated reduced lung function (pinteraction=0.007). This interaction was stronger in infants with Black African ancestry (pinteraction=0.001) and nonexistent in children with mixed ancestry (pinteraction=0.876).ConclusionsPM10and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.
Potential impacts of a novel integrated extracorporeal-CPR workflow using an interventional radiology and immediate whole-body computed tomography system in the emergency department
Authors: Hayashida Kei , Kinoshita Takahiro , Yamakawa Kazuma , Miyara Santiago J. , Becker Lance B. , Fujimi Satoshi 
Published: January 2020

AbstractExtracorporeal cardiopulmonary resuscitation (ECPR) can be associated with increased survival and neurologic benefits in selected patients with out-of-hospital cardiac arrest (OHCA). However, there remains insufficient evidence to recommend the routine use of ECPR for patients with OHCA. A novel integrated trauma workflow concept that utilizes a sliding computed tomography (CT) scanner and interventional radiology (IR) system, named a hybrid emergency room system (HERS), allowing emergency therapeutic interventions and CT examination without relocating trauma patients, has recently evolved in Japan. HERS can drastically shorten the ECPR implementation time and more quickly facilitate definitive interventions than the conventional advanced cardiovascular life support workflow. Herein, we discuss our novel workflow concept using HERS on ECPR for patients with OHCA.
Mycoplasma pneumoniae pneumonia associated thrombosis at Beijing Children’s hospital
Authors: Liu Jinrong , He Ruxuan , Wu Runhui , Wang Bei , Xu Hui , Zhang Yue , Li Huimin , Zhao Shunying 
Published: January 2020

AbstractBackgroundWith the increase of awareness ofmycoplasma pneumoniaepneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis.MethodsWe retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children’s Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes.ResultsForty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, β2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3–1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough.ConclusionsSMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.