Miracle-dz/UniFAR-FTUs huggingface dataset:
Racial Differences in Associations of Blood Pressure Components in Young Adulthood With Incident Cardiovascular Disease by Middle Age: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Importance Data are sparse regarding which blood pressure (BP) components in young adulthood optimally determine cardiovascular disease (CVD) by middle age. Objectives To assess which BP components best determine incident CVD events in young adults and determine whether these associations vary by race and age at BP measurement. Design, Setting, and Participants Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, this study assessed the longitudinal race-stratified associations between BP and cardiovascular outcomes. CARDIA is a community-based cohort that recruited black and white individuals (age range, 18-30 years) from March 26, 1985, through June 7, 1986. CARDIA followed up participants for up to 28 years, and 94% of the surviving cohort completed at least 1 telephone interview or examination from August 2009 through August 2014. Exposures Blood pressures measubred at baseline (Y0) and 15 years later (Y15). Main Outcomes and Measures Composite CVD events, including coronary heart disease, stroke, heart failure, and other vascular diseases. Results A total of 4880 participants participated in the study (mean [SD] age, 24.9 [3.6] years at Y0 and 25.0 [3.6] years at Y15; 2223 male [45.6%] at Y0 and 1800 [44.2%] at Y15; 2657 female [54.4%] at Y0 and 2277 [55.8%] at Y0; 2473 black individuals [50.7%] at Y0 and 1994 [48.9%] at Y15; and 2407 white individuals [49.3%] at Y0 and 2083 [51.1%] at Y15). The mean SBP/DBP was 112/69 mm Hg in blacks and 109/68 mm Hg in whites at Y0 and 117/77 mm Hg in blacks and 110/72 mm Hg in whites at Y15. During a 25-year follow-up from Y0, 210 CVD events occurred (twice as many events in blacks [n = 140] compared with whites), of which 131 (87 in blacks) occurred after Y15. With adjustments for covariates, results from Cox proportional hazards models, including SBP and DBP, jointly suggested that, at Y0, SBP (hazard ratio [HR] per 1-SD increase, 1.32; 95% CI, 1.09-1.61) but not DBP (HR, 1.05; 95% CI, 0.88-1.26) was associated with CVD risk in blacks, whereas DBP (HR, 1.74; 95% CI, 1.21-2.50) but not SBP (HR, 0.82; 95% CI, 0.57-1.18) was associated with CVD risk in whites. At Y15, SBP was the strongest indicator of CVD in blacks (HR, 1.64; 95% CI, 1.25-2.16) and whites (HR, 1.67; 95% CI, 1.02-2.69). Conclusions and Relevance This study questions the classic view that DBP is more able to identify future CVD events than SBP in all individuals younger than 50 years. In young adulthood, SBP in black individuals and DBP in white individuals were the most robust indicators of future CVD. In middle-age, SBP in both races identified risk of incident CVD.
Does the Danger model shed any light on central tolerance?: A response to Al‐Yassin

In a commentary on our 1996 publication[1], Al-Yassin suggests that we mischaracterized the results of the classical neonatal tolerance experiments of Billingham, Brent, and Medawar (BBM)[2] when we stated that "[BBM} found that rodents injected at birth with hemopoietic cells from a genetically different donor were later able to accept transplants from the same donor". Al-Yassin points out that "BBM could only reliably induce tolerance by giving fetal mice allogeneic cells" and "BBM concluded that neonatal mice were in a 'null' period, during which inoculation with MHC-incompatible cells had no effect, i.e. the recipient mice became neither tolerant nor primed against the 'test' graft". As to the charge of mischaracterization, we plead "guilty". We referenced the wrong paper. This article is protected by copyright. All rights reserved.
Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this guideline is to provide a synopsis of best clinical practices in the rehabilitative care of adults recovering from stroke. Methods— Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council’s Scientific Statement Oversight Committee and the AHA’s Manuscript Oversight Committee. The panel reviewed relevant articles on adults using computerized searches of the medical literature through 2014. The evidence is organized within the context of the AHA framework and is classified according to the joint AHA/American College of Cardiology and supplementary AHA methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive AHA internal and external peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. Results— Stroke rehabilitation requires a sustained and coordinated effort from a large team, including the patient and his or her goals, family and friends, other caregivers (eg, personal care attendants), physicians, nurses, physical and occupational therapists, speech-language pathologists, recreation therapists, psychologists, nutritionists, social workers, and others. Communication and coordination among these team members are paramount in maximizing the effectiveness and efficiency of rehabilitation and underlie this entire guideline. Without communication and coordination, isolated efforts to rehabilitate the stroke survivor are unlikely to achieve their full potential. Conclusions— As systems of care evolve in response to healthcare reform efforts, postacute care and rehabilitation are often considered a costly area of care to be trimmed but without recognition of their clinical impact and ability to reduce the risk of downstream medical morbidity resulting from immobility, depression, loss of autonomy, and reduced functional independence. The provision of comprehensive rehabilitation programs with adequate resources, dose, and duration is an essential aspect of stroke care and should be a priority in these redesign efforts. (Stroke.2016;47:e98-e169. DOI: 10.1161/STR.0000000000000098.)
Using machine learning for sequence-level automated MRI protocol selection in neuroradiology

Incorrect imaging protocol selection can lead to important clinical findings being missed, contributing to both wasted health care resources and patient harm. We present a machine learning method for analyzing the unstructured text of clinical indications and patient demographics from magnetic resonance imaging (MRI) orders to automatically protocol MRI procedures at the sequence level. We compared 3 machine learning models - support vector machine, gradient boosting machine, and random forest - to a baseline model that predicted the most common protocol for all observations in our test set. The gradient boosting machine model significantly outperformed the baseline and demonstrated the best performance of the 3 models in terms of accuracy (95%), precision (86%), recall (80%), and Hamming loss (0.0487). This demonstrates the feasibility of automating sequence selection by applying machine learning to MRI orders. Automated sequence selection has important safety, quality, and financial implications and may facilitate improvements in the quality and safety of medical imaging service delivery.
New Insights into the Evolution of the W Chromosome in Lepidoptera

Moths and butterflies (Lepidoptera) represent the most diverse group of animals with heterogametic females. Although the vast majority of species has a WZ/ZZ (female/male) sex chromosome system, it is generally accepted that the ancestral system was Z/ZZ and the W chromosome has evolved in a common ancestor of Tischeriidae and Ditrysia. However, the lack of data on sex chromosomes in lower Lepidoptera has prevented a formal test of this hypothesis. Here, we performed a detailed analysis of sex chromosomes in Tischeria ekebladella (Tischeriidae) and 3 species representing lower Ditrysia, Cameraria ohridella (Gracillariidae), Plutella xylostella (Plutellidae), and Tineola bisselliella (Tineidae). Using comparative genomic hybridization we show that the first 3 species have well-differentiated W chromosomes, which vary considerably in their molecular composition, whereas T. bisselliella has no W chromosome. Furthermore, our results suggest the presence of neo-sex chromosomes in C. ohridella. For Z chromosomes, we selected 5 genes evenly distributed along the Z chromosome in ditrysian model species and tested their Z-linkage using qPCR. The tested genes (Henna, laminin A, Paramyosin, Tyrosine hydroxylase, and 6-Phosphogluconate dehydrogenase) proved to be Z-linked in all species examined. The conserved synteny of the Z chromosome across Tischeriidae and Ditrysia, along with the W chromosome absence in the lower ditrysian families Psychidae and Tineidae, suggests a possible independent origin of the W chromosomes in these 2 lineages.
Interactions of established risk factors and a GWAS-based genetic risk score on the risk of venous thromboembolism

Summary Multiple genetic and environmental risk factors contribute to venous thromboembolism (VTE) risk. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of VTE and may identify opportunities for targeted prevention and treatment. It was our aim to examine the main effects and the potential effect-modification between single nucleotide polymorphisms (SNPs) at established loci and lifestyle risk factors for VTE. We performed a nested case-control study using data on 1,040 incident VTE cases and 16,936 controls from the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood, were selected as participants in a previous genome-wide association study (GWAS), and completed a biennial questionnaire at time of blood draw. We selected SNPs that were associated with VTE risk in previous GWAS studies. A genetic risk score (GRS) was constructed to evaluate the combined effect of the 16 SNPs that have reached genome-wide significance in previous GWAS of VTE. Interactions between SNPs and VTE risk factors (BMI and smoking) were also assessed. We found a significant association between our GRS and VTE risk. The risk of VTE among individuals in the highest GRS tertile was 2.02 times that of individuals in the lowest GRS tertile (p-trend = 9.69x10-19). The OR was 1.52 (p=1.03x10-8) for participants in the highest GRS tertile compared to those in the medium GRS tertile. However, while BMI and smoking were associated with VTE, and their effects were additive to each other we did not observe any significant multiplicative gene-environment interactions. Supplementary Material to this article is available online at www.thrombosis-online.com.
Activation of JAK/STAT3 restores NK‐cell function and improves immune defense after brain ischemia

Stroke‐induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/ or producing cytokines such as IFN‐γ. Because the phenotype and function of peripheral NK cells have been widely investigated in ischemic stroke, nCounter Inflammation Gene Array Analysis was used to build immune‐related gene profiles of NK cells to comprehensively analyze the molecular signature of NK cells after ischemic brain injury. We observed distinct gene expression profiles reflecting different splenic NK‐cell phenotypes and functional properties across the time course of transient middle cerebral artery occlusion (MCAO). Based on gene expression and pathway‐network analysis, lower expression levels of signal transducer and activator of transcription‐3 (STAT3) were observed in animals with MCAO compared with sham control animals. Genetic activation of STAT3 through the introduction of STAT3 clustered regularly interspaced short palindromic repeats (CRISPR) plasmid prevented the loss of NK‐cell‐derived IFN‐γ production after MCAO, together with reduced bacterial burden and mortality. Our data suggest that brain ischemia impairs NK‐cell‐mediated immune defense in the periphery, at least in part through the JAK‐STAT3 pathway, which can be readdressed by modulating STAT3 activation status. —Jin, W. ‐N. , Ducruet, A. F. , Liu, Q. , Shi, S. X. ‐Y. , Waters, M. , Zou, M. , Sheth, K. N, Gonzales, R. , Shi, F. ‐D. Activation of JAK/ STAT3 restores NK‐cell function and improves immune defense after brain ischemia. FASEB J. 32,2757–2767 (2018). www.fasebj. org
CD56bright NK cells exhibit potent antitumor responses following IL-15 priming

NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production. Primed CD56bright cells from leukemia patients demonstrated enhanced responses to autologous blasts in vitro, and primed CD56bright cells controlled leukemia cells in vivo in a murine xenograft model. Primed CD56bright cells from multiple myeloma (MM) patients displayed superior responses to autologous myeloma targets, and furthermore, CD56bright NK cells from MM patients primed with the IL-15 receptor agonist ALT-803 in vivo displayed enhanced ex vivo functional responses to MM targets. Effector mechanisms contributing to IL-15–based priming included improved cytotoxic protein expression, target cell conjugation, and LFA-1–, CD2-, and NKG2D-dependent activation of NK cells. Finally, IL-15 robustly stimulated the PI3K/Akt/mTOR and MEK/ERK pathways in CD56bright compared with CD56dim NK cells, and blockade of these pathways attenuated antitumor responses. These findings identify CD56bright NK cells as potent antitumor effectors that warrant further investigation as a cancer immunotherapy.
Ischemic preconditioning enhances critical power during a 3 minute all-out cycling test

ABSTRACT This study tested the hypothesis that ischemic preconditioning (IPC) would increase critical power (CP) during a 3 minute all-out cycling test. Twelve males completed two 3 minute all-out cycling tests, in a crossover design, separated by 7 days. These tests were preceded by IPC (4 x 5 minute intervals at 220 mmHg bilateral leg occlusion) or SHAM treatment (4 x 5 minute intervals at 20 mmHg bilateral leg occlusion). CP was calculated as the mean power output during the final 30 s of the 3 minute test with W′ taken as the total work done above CP. Muscle oxygenation was measured throughout the exercise period. There was a 15.3 ± 0.3% decrease in muscle oxygenation (TSI; [Tissue saturation index]) during the IPC stimulus, relative to SHAM. CP was significantly increased (241 ± 65 W vs. 234 ± 67 W), whereas W′ (18.4 ± 3.8 vs 17.9 ± 3.7 kJ) and total work done (TWD) were not different (61.1 ± 12.7 vs 60.8 ± 12.7 kJ), between the IPC and SHAM trials. IPC enhanced CP during a 3 minute all-out cycling test without impacting W′ or TWD. The improved CP after IPC might contribute towards the effect of IPC on endurance performance.
Socioeconomic inequalities in breast cancer incidence and mortality in Europe—a systematic review and meta-analysis

Background: Breast cancer is the leading cause of female cancer in Europe and is estimated to affect more than one in 10 women. Higher socioeconomic status has been linked to higher incidence but lower case fatality, while the impact on mortality is ambiguous. Methods: We performed a systematic literature review and meta-analysis on studies on association between socioeconomic status and breast cancer outcomes in Europe, with a focus on effects of confounding factors. Summary relative risks (SRRs) were calculated. Results: The systematic review included 25 articles of which 8 studied incidence, 10 case fatality and 8 mortality. The meta-analysis showed a significantly increased incidence (SRR 1.25, 1.17–1.32), a significantly decreased case fatality (SRR 0.72, 0.63–0.81) and a significantly increased mortality (SRR 1.16, 1.10–1.23) for women with higher socioeconomic status. The association for incidence became insignificant when reproductive factors were included. Case fatality remained significant after controlling for tumour characteristics, treatment factors, comorbidity and lifestyle factors. Mortality remained significant after controlling for reproductive factors. Conclusion: Women with higher socioeconomic status show significantly higher breast cancer incidence, which may be explained by reproductive factors, mammography screening, hormone replacement therapy and lifestyle factors. Lower case fatality for women with higher socioeconomic status may be partly explained by differences in tumour characteristics, treatment factors, comorbidity and lifestyle factors. Several factors linked to breast cancer risk and outcome, such as lower screening attendance for women with lower socioeconomic status, are suitable targets for policy intervention aimed at reducing socioeconomic-related inequalities in health outcomes.
Expert position paper on air pollution and cardiovascular disease.

Air pollution has wide-ranging and deleterious effects on human health and is a major issue for the global community. The Global Burden of Disease study has described the worldwide impact of air pollution with as many as 3.1 million of 52.8 million all-cause and all-age deaths being attributable to ambient air pollution in the year 2010.1 Moreover, ambient air pollution ranked ninth among the modifiable disease risk factors, being listed above other commonly recognized factors, such as low physical activity, a high-sodium diet, high cholesterol, and drug use. Finally, air pollution accounts for 3.1% of global disability-adjusted life years, an index that measures the time spent in states of reduced health.1 Although it is intuitive that air pollution is an important stimulus for the development and exacerbation of respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and lung cancer, there is generally less public awareness of its substantial impact on cardiovascular disease. Historically, the 1952 Great Smog of London led to an increase in cardiovascular death as well as deaths due to respiratory disease. Subsequent studies in the 1990s, such as the Harvard Six Cities2 and American Cancer Society cohort studies,2,3 established an enduring positive association between long-term exposure to air pollution and total and cardiovascular mortality, mainly due to coronary artery disease.4 In Europe, the first study that supported this association between long-term exposure and mortality was the Netherlands Cohort Study on Diet and Cancer.5 Associations with cardiovascular morbidity and mortality are also seen with short-term (e.g. day-to-day fluctuations) pollutant exposures of residents in large urban areas worldwide, including the United States of America6 …
Structural, optical, room-temperature and low-temperature magnetic properties of Mg–Zn nanoferrite ceramics

ABSTRACT Mg–Zn nanocrystalline ferrites (Mg1−xZnxFe2O4, where x = 0.0 to 1.0) were synthesized by the citrate gel auto-combustion route. XRD revealed the formation of nano-sized particles with cubic spinel structure. Lattice constant and specific surface area increased with Zn substitution. SEM micrographs revealed inhomogeneous grains with agglomerates; EDS spectra confirmed the stoichiometry. HRTEM images showed agglomerated nanoparticles with average particle sizes of 21 nm and 16 nm for x = 0.6 and 1.0, respectively, and lattice fringe images and SAED patterns showed nanocrystalline characteristics corroborating the XRD results. FTIR and Raman spectra recorded at room temperature confirmed the spinel structure of ferrites. VSM technique at room temperature used to measure magnetic properties. MS and HC were found to decrease with increases in the Zn concentration in Mg–Zn ferrites due to a weakening of the A–B interaction and decrease in the particle size and surface effect. Low-temperature magnetic studies were carried out in the ZFC and FC modes using SQUIDS by applying 100 Oe between temperatures of 5 and 400 K, and magnetic isotherms were recorded at temperatures of 51 and 310 K. The study revealed the superparamagnetic nature of the synthesized samples showing that the blocking temperature (TB) depends on interparticle interactions.
ZBTB48 is both a vertebrate telomere‐binding protein and a transcriptional activator

Telomeres constitute the ends of linear chromosomes and together with the shelterin complex form a structure essential for genome maintenance and stability. In addition to the constitutive binding of the shelterin complex, other direct, yet more transient interactions are mediated by the CST complex and HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors. Recently, the Kruppel‐like zinc finger protein ZBTB48/HKR3/TZAP has been described as a novel telomere‐associated factor in the vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric and to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.