Miracle-dz/UniFAR-FTUs huggingface dataset:
High‐density lipoprotein lipid peroxidation as a molecular signature of the risk for developing cardiovascular disease: Results from MASHAD cohort

High‐density lipoprotein (HDL) function rather than level may better predict cardiovascular disease (CVD). However, the contribution of the impaired antioxidant function of HDL that is associated with increased HDL lipid peroxidation (HDLox) to the development of clinical CVD remains unclear. We have investigated the association between serum HDLox with incident CVD outcomes in Mashhad cohort. Three‐hundred and thirty individuals who had a median follow‐up period of 7 years were recruited as part of the cohort. The primary end point was cardiovascular event, including myocardial infarction, stable angina, unstable angina, or coronary revascularization. In both univariate/multivariate analyses adjusted for traditional CVD risk factors, HDLox was an independent risk factor for CVD (odds ratio, 1.62; 95% confidence interval, 1.41–1.86; p < 0.001). For every increase in HDLox by 0.1 unit, there was an increase in CVD risk by 1.62‐fold. In an adjusted analysis, there was a >2.5‐fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point of 1.06 compared to those with lower scores, suggesting HDLox > 1.06 is related to the impaired HDL oxidant function and in turn exposed to elevated risk of CVD outcomes (hazard ratio, 2.72; 95% CI, 1.88–3.94). Higher HDLox is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population‐based cohort.
Association of high mobility group box 1 protein with coronary artery disease

Background Recently, the role of inflammation in coronary artery disease and the association of inflammatory biomarkers with adverse outcomes have been investigated in many studies. We investigated the relationship between high serum mobility group box 1 protein levels and established risk factors for coronary artery disease. Methods Fifty-five patients who presented to our Cardiovascular Surgery Clinic and subsequently underwent coronary artery bypass surgery for coronary artery disease and 50 healthy subjects presenting to the cardiology outpatient clinic without any cardiovascular problem were included in the study. The mean age was 61.47 ± 9.38 years for patients and 58.20 ± 10.15 years for controls. Results There was no statistically significant difference between groups with respect to age or sex. Family history of coronary artery disease, aspirin use, hypertension, and type 2 diabetes were significantly more prevalent in the patient group versus the control group. A significant difference was found between patients and healthy controls with respect to high mobility group box 1 protein levels (p = 0.001). Conclusions Serum high mobility group box 1 protein was significantly increased in patients with coronary artery disease in comparison to healthy subjects. No associations were found between high mobility group box 1 protein level and certain risk factors for coronary artery disease.
Blood donation is an act of benevolence rather than altruism.

OBJECTIVES Blood donation is described as an archetypal altruistic behavior, and recruitment/retention campaigns emphasize altruism. Here, a benevolence hypothesis for blood donation (both the donor and recipient benefit) rather than the altruism hypothesis (only the recipient gains) is proposed. DESIGN Three United Kingdom-based studies contrasted benevolence and altruism: (a) a 6-month prospective study of blood donor behavior (Study 1: N = 957), (b) a cross-sectional study of blood donors' intentions (Study 2: N = 333), and (c) an experimental study examining the effect of benevolent and altruistic messages on willingness to help across high- and low-cost helping behaviors for committed and noncommitted blood donors (Study 3: N = 200). MAIN OUTCOME Donor behavior and intentions-willingness. MEASURES Beliefs in personal and societal benefit (Time 1) and actual donations (Time 2) were assessed in Study 1; beliefs in benevolence, altruism, hedonism, and kinship along with donation intentions were assessed in Study 2; and empathy, donor commitment, and willingness to donate blood, money, fund-raise, and staff a telephone helpline were assessed in Study 3. RESULTS Beliefs in personal rather than societal benefit predicted actual future donation. A path model showed that only beliefs in benevolence were associated with intentions to donate. Committed blood donors were more willing to donate blood when exposed to a benevolent message rather than an altruistic one. This effect was not observed for other forms of helping. CONCLUSIONS The benevolence hypothesis is supported, suggesting that blood donor motivation is partly selfish. Blood donation campaigns should focus on benevolent rather than purely altruistic messages.
Structural basis for activity of TRIC counter-ion channels in calcium release

Significance Triggered release of calcium from intracellular stores is crucial for diverse cellular processes, including excitation–contraction coupling in muscle. Trimeric intracellular cation (TRIC) channels are essential components of endoplasmic reticulum/ sarcoplasmic reticulum (ER/SR) membranes, but their physiological roles have been unclear. Studies reported here elucidate a counter-ion mechanism by which TRIC channels facilitate calcium release. Calcium depletion during release through inositol 1,4,5-trisphosphate or ryanodine receptors depolarizes the ER/SR membrane potential, which retards continued calcium release. We show that Ca2+ binding to TRIC channels stabilizes a nonconductive conformation; however, Ca2+-free TRIC, as is generated during calcium release, frees a gating residue on a voltage-sensing helix to move out of blockage in response to membrane depolarization. Resulting K+ counter-ion currents can restore polarization for continued calcium release. Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca2+ from intracellular stores. TRIC activity is controlled by voltage and Ca2+ modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca2+-bound and Ca2+-free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. The TRIC channels are symmetric trimers, wherein we find a pore in each protomer that is gated by a highly conserved lysine residue. In the resting state, Ca2+ binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca2+ release, luminal Ca2+ depletion removes inhibition to permit the lysine-bearing and voltage-sensing helix to move in response to consequent membrane hyperpolarization. Diacylglycerol is found at interprotomer interfaces, suggesting a role in metabolic control.
Systematic review of clinical outcome reporting in randomised controlled trials of burn care

Introduction Systematic reviews collate trial data to provide evidence to support clinical decision-making. For effective synthesis, there must be consistency in outcome reporting. There is no agreed set of outcomes for reporting the effect of burn care interventions. Issues with outcome reporting have been identified, although not systematically investigated. This study gathers empirical evidence on any variation in outcome reporting and assesses the need for a core outcome set for burn care research. Methods Electronic searches of four search engines were undertaken from January 2012 to December 2016 for randomised controlled trials (RCTs), using medical subject headings and free text terms including ‘burn’, ‘scald’ ‘thermal injury’ and ‘RCT’. Two authors independently screened papers, extracted outcomes verbatim and recorded the timing of outcome measurement. Duplicate outcomes (exact wording ± different spelling), similar outcomes (albumin in blood, serum albumin) and identical outcomes measured at different times were removed. Variation in outcome reporting was determined by assessing the number of unique outcomes reported across all included trials. Outcomes were classified into domains. Bias was reduced using five researchers and a patient working independently and together. Results 147 trials were included, of which 127 (86.4%) were RCTs, 13 (8.8%) pilot studies and 7 (4.8%) RCT protocols. 1494 verbatim clinical outcomes were reported; 955 were unique. 76.8% of outcomes were measured within 6 months of injury. Commonly reported outcomes were defined differently. Numbers of unique outcomes per trial varied from one to 37 (median 9; IQR 5,13). No single outcome was reported across all studies demonstrating inconsistency of reporting. Outcomes were classified into 54 domains. Numbers of outcomes per domain ranged from 1 to 166 (median 11; IQR 3,24). Conclusions This review has demonstrated heterogeneity in outcome reporting in burn care research which will hinder amalgamation of study data. We recommend the development of a Core Outcome Set. PROSPERO registration number CRD42017060908.
A wave of WNT signaling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells

ABSTRACT Long-range signaling by morphogens and their inhibitors define embryonic patterning yet quantitative data and models are rare, especially in humans. Here, we use a human embryonic stem cell micropattern system to model formation of the primitive streak (PS) by WNT. In the pluripotent state, E-cadherin (E-CAD) transduces boundary forces to focus WNT signaling to the colony border. Following application of WNT ligand, E-CAD mediates a front or wave of epithelial-to-mesenchymal (EMT) conversion analogous to PS extension in an embryo. By knocking out the secreted WNT inhibitors active in our system, we show that DKK1 alone controls the extent and duration of patterning. The NODAL inhibitor cerberus 1 acts downstream of WNT to refine the endoderm versus mesoderm fate choice. Our EMT wave is a generic property of a bistable system with diffusion and we present a single quantitative model that describes both the wave and our knockout data. Highlighted Article: Analysis of human embryonic stem cell micropatterns reveals that E-cadherin mediates a WNT-induced epithelial-to-mesenchymal wave analogous to primitive streak extension and DKK1 controls the extent and duration of this patterning.
Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans.

BACKGROUND Choline is an essential nutrient for humans, and part of this requirement is met by endogenous synthesis catalyzed by hepatic phosphatidylethanolamine N-methyltransferase (PEMT). PEMT activity is difficult to estimate in humans because it requires a liver biopsy. Previously, we showed that mice that lack functional PEMT have dramatically reduced concentrations of docosahexaenoic acid (DHA; 22:6n-3) in plasma and of liver phosphatidylcholine (PtdCho)-a phospholipid formed by PEMT. OBJECTIVE The objective was to evaluate plasma PtdCho-DHA concentrations as a noninvasive marker of liver PEMT activity in humans. DESIGN Plasma PtdCho-DHA concentrations were measured in 72 humans before and after they consumed a low-choline diet, and correlations were analyzed in relation to estrogen status, PEMT polymorphism rs12325817, the ratio of plasma S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy), and dietary choline intake; all of these factors are associated with changes in liver PEMT activity. PtdCho-DHA and PEMT activity were also measured in human liver specimens. RESULTS At baseline, the portion of PtdCho species containing DHA (pmol PtdCho-DHA/nmol PtdCho) was higher in premenopausal women than in men and postmenopausal women (P < 0.01). This ratio was lower in premenopausal women with the rs12325817 polymorphism in the PEMT gene (P < 0.05), and PtdCho-DHA concentration and PEMT activity were lower in human liver samples from women who were homozygous for PEMT rs12325817 (P < 0.05). The ratio of DHA-PtdCho to PtdCho in plasma was directly correlated with the ratio of AdoMet to AdoHcy (P = 0.0001). The portion of PtdCho species containing DHA in plasma was altered in subjects who consumed a low-choline diet. CONCLUSION PtdCho-DHA may be useful as a surrogate marker for in vivo hepatic PEMT activity in humans. This trial was registered at clinicaltrials.gov as NCT00065546.
Stimulus-Driven Brain Rhythms within the Alpha Band: The Attentional-Modulation Conundrum

Two largely independent research lines use rhythmic sensory stimulation to study visual processing. Despite the use of strikingly similar experimental paradigms, they differ crucially in their notion of the stimulus-driven periodic brain responses: one regards them mostly as synchronized (entrained) intrinsic brain rhythms; the other assumes they are predominantly evoked responses [classically termed steady-state responses (SSRs)] that add to the ongoing brain activity. This conceptual difference can produce contradictory predictions about, and interpretations of, experimental outcomes. The effect of spatial attention on brain rhythms in the alpha band (8–13 Hz) is one such instance: alpha-range SSRs have typically been found to increase in power when participants focus their spatial attention on laterally presented stimuli, in line with a gain control of the visual evoked response. In nearly identical experiments, retinotopic decreases in entrained alpha-band power have been reported, in line with the inhibitory function of intrinsic alpha. Here we reconcile these contradictory findings by showing that they result from a small but far-reaching difference between two common approaches to EEG spectral decomposition. In a new analysis of previously published human EEG data, recorded during bilateral rhythmic visual stimulation, we find the typical SSR gain effect when emphasizing stimulus-locked neural activity and the typical retinotopic alpha suppression when focusing on ongoing rhythms. These opposite but parallel effects suggest that spatial attention may bias the neural processing of dynamic visual stimulation via two complementary neural mechanisms. SIGNIFICANCE STATEMENT Attending to a visual stimulus strengthens its representation in visual cortex and leads to a retinotopic suppression of spontaneous alpha rhythms. To further investigate this process, researchers often attempt to phase lock, or entrain, alpha through rhythmic visual stimulation under the assumption that this entrained alpha retains the characteristics of spontaneous alpha. Instead, we show that the part of the brain response that is phase locked to the visual stimulation increased with attention (as do steady-state evoked potentials), while the typical suppression was only present in non-stimulus-locked alpha activity. The opposite signs of these effects suggest that attentional modulation of dynamic visual stimulation relies on two parallel cortical mechanisms—retinotopic alpha suppression and increased temporal tracking.
Analysis of the Influence of Age, BMI, and WHtR on Body Mass Acceptance, Attitudes, and Motivation towards Body Mass Reduction in Overweight and Obese Caucasian Women

The emotional consequences of excessive body mass, associated with body image and acceptance, have become a global public health challenge as they may decrease the general well-being and hinder weight loss in overweight and obese individuals. Therefore, this study aimed to analyze the influence of age, body mass index (BMI), and waist-to-height ratio (WHtR) on body mass acceptance, attitudes, and motivation toward body mass reduction in overweight and obese Caucasian women with excessive abdominal fat. The previously validated BodyMass–DRama (Body Mass–Dietary Restrictions: Acceptance, Motivation, Attitudes) questionnaire was applied in this study. The declared acceptance, attitudes and motivation towards body mass reduction were compared between subgroups based on age (20–40, 40–50, and 50–60 years), BMI (25.0–30.0, 30.0–35.0, and ≥35.0 kg/m2), and quartiles of WHtR. The age, BMI and WHtR were stated to be associated with declared acceptance, attitudes, and motivation towards body mass reduction. The different age groups indicated the following as the reasons for excessive body mass: young respondents—low physical activity and consumption of sweets; middle-aged ones—large/irregular meals; aging ones—large/irregular meals and low physical activity (p = 0.0161). While describing motivation toward body mass reduction, young respondents indicated the role of a physician or dietitian (p = 0.0012) or someone who can control them (p = 0.0044), as well as their expectation to be more successful at work after body mass reduction (p = 0.0045), while the aging ones indicated appreciation and plaudits from others (p = 0.0264) as a motivating factor. Respondents with the highest BMI declared having spending free time actively constricted (p = 0.0007); they declared more often than others of feeling exhausted (p = 0.0395) or tired all the time (p = 0.0445), but less often of feeling full of joy (p = 0.0457) or full of energy (p <0.0001). Respondents with moderate WHtR declared less often than others that they expect to enjoy socializing (p = 0.0376), but more often to be able to have a better vacation after body mass reduction (p = 0.0128), while those with the lowest WHtR expected to be more physically active (p = 0.0487). Women with the highest WHtR most commonly indicated external pressure from relatives or co-workers as a motivating factor for body mass reduction (p = 0.0435). Due to these differences between Caucasian women with excessive body mass, the approach of physicians and dietitians, as well as methods applied to motivate patients, need to be customized.
Zamia (Cycadales: Zamiaceae) on Puerto Rico: asymmetric genetic differentiation and the hypothesis of multiple introductions.

PREMISE OF THE STUDY This study of Zamia in Puerto Rico is the most intensive population genetics investigation of a cycad to date in terms of number of markers, and one of few microsatellite DNA studies of plants from the highly critical Caribbean biodiversity hotspot. Three distinctive Zamia taxa occur on the island: Z. erosa on the north coast, and Z. portoricensis and Z. pumila, both in the south. Their relationships are largely unknown. We tested three hypotheses about their genetic diversity, including the possibility of multiple introductions. METHODS We used 31 microsatellite loci across 10 populations and analyzed the data with AMOVA, Bayesian clustering, and ABC coalescent modeling. KEY RESULTS Puerto Rican zamias exhibit an amalgam of patterns of genetic differentiation that have been reported for cycads. Overall, the taxa are slightly inbred, with high infra-populational variation and little evidence of recent bottlenecks. Zamia erosa exhibits a more than threefold greater degree of population differentiation than the other two taxa. Admixture is evident only between Z. portoricensis and Z. pumila. Zamia portoricensis is inferred to be the youngest taxon on the island, on the basis of estimates of coalescence time and effective population size. A selective sweep may be underway in a small population of Z. erosa in a saline environment. CONCLUSIONS Zamia erosa may represent an independent introduction into Puerto Rico; Z. portoricensis and Z. pumila fit a scenario of allopatric speciation. This will be explored further in the context of genetic analysis across the entire Caribbean region.
Extraction of Acids and Bases from Aqueous Phase to a Pseudoprotic Ionic Liquid

We report experiments on the extraction of acids and bases from an aqueous phase to a pseudoprotic ionic liquid phase consisting of an equimolar mixture of trihexylamine and octanoic acid. We observed the extraction of a wide range of acids and bases, and investigated the mechanism of extraction in detail. Our results confirmed the observation of the Hofmeister effect in these systems reported in our previous work, where the extent of the extraction of copper salts was significantly influenced by the interactions between extracted inorganic anions and the organic phase. Our results further demonstrated that the organic layer served as a “floating buffer” capable of stabilizing the pH of an acidic or alkaline aqueous phase. The results tie current interest in protic and pseudoprotic ionic liquids to earlier work on the extraction of acids using amine and acid–base couples as extraction agents in an inert organic solvent.
Toxicities of CD19 CAR‐T cell immunotherapy

CD19‐targeted chimeric antigen receptor (CAR)‐modified T (CAR‐T) cell immunotherapy has demonstrated impressive results in B‐cell malignancies, and CAR‐T cell therapies targeting other antigens are in development for other cancers. Cytokine release syndrome (CRS) and neurotoxicity can be life‐threatening in a subset of patients. The severity of CRS and neurotoxicity can be impacted by the disease burden, lymphodepletion regimen, and CAR‐T cell dose. Tocilizumab and corticosteroids have been used to manage these toxicities, enabling CD19 CAR‐T cells to be administered without obvious compromise in efficacy. Consensus criteria for grading and managing toxicities will facilitate the widespread application of this treatment modality.
Sinus Node Dysfunction Unmasked during Dobutamine Stress Echocardiography

Sinus bradycardia and associated isorhythmic AV dissociation may be seen during dobutamine stress echocardiography. This phenomenon is usually considered a benign peri-procedural event and is thought to be secondary to the Bezold-Jarisch reflex, with profound heart rate decrease secondary to a marked increased in vagal efferent discharge. To the best of our knowledge, dobutamine stress echocardiography unmasking clinically relevant sinus node dysfunction has never been reported. We report a case of a 50-year-old man presenting with chest pain and a history of syncope, who had worsening sinus bradycardia with isorhythmic AV dissociation during dobutamine stress echocardiography. An invasive electrophysiological study revealed marked sinus node dysfunction. The patient was referred for the insertion of a permanent pacemaker for sinus node dysfunction, chronotropic incompetence and symptomatic bradycardia. Dobutamine-associated bradycardia may not always be a benign peri-procedural physiologic effect, as in this case it may unmask clinically significant sinus node dysfunction.
The Gap Between Science and Practice: A Conversation

The authors, friends, colleagues, and collaborators for almost 60 years engage in an informal discussion concerning the gap between science and practice. They identify some sources of the problem, some manifestations of it, and point the way to some possible solutions. The articles in this special section, because of their use of data collected in a naturalistic setting and the prominent role of clinicians, are viewed as one of many promising directions for the reconciliation of the activity of researchers and the needs of clinicians.