Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations between interarm differences in blood pressure and cardiovascular disease outcomes: protocol for an individual patient data meta-analysis and development of a prognostic algorithm

Introduction Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) Is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. Methods and analysis This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. Ethics and dissemination This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. PROSPERO registration number CRD42015031227.
Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil

Background The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. Methodology/Principal findings We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. Conclusions/Significance The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions.
Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay

Objective With a high-sensitivity troponin assay, it may be possible to exclude acute myocardial infarction with a single blood test on arrival in the emergency department by using a novel ‘rule out’ cut-off set at the limit of detection of the assay. We aimed to determine whether this can also be achieved using a contemporary sensitive troponin assay that does not meet ‘high-sensitivity’ criteria. Methods In a prospective diagnostic cohort study, we included patients presenting to the emergency department with suspected cardiac chest pain. For this secondary analysis, serum samples drawn on arrival were tested using a contemporary sensitive troponin I assay (s-cTnI; Siemens Ultra ADVIA Centaur, 99th percentile 40 ng/L, limit of detection 6 ng/L). Acute myocardial infarction was adjudicated by two independent investigators based on reference standard troponin testing ≥12 h after symptom onset. Results Of 414 participants, 70 (16.9%) had acute myocardial infarction and 205 (49.5%) had initial s-cTnI concentrations below the limit of detection. Using the limit of detection as a ‘rule out’ cut-off gave a sensitivity of 94.3% (95% CI 86.0–98.4%) for acute myocardial infarction. If only patients with s-cTnI below the limit of detection and no electrocardiogram ischaemia were considered to have acute myocardial infarction ‘ruled out’ (41.8% of the cohort, n = 174), sensitivity would rise to 97.1% (90.1–99.7%) and negative predictive value to 98.8% (95.9–99.9%). Conclusions Acute myocardial infarction cannot be excluded in patients with s-cTnI concentrations below the limit of detection using the contemporary sensitive assay evaluated. Future work with this assay should focus on serial sampling over 1–3 h and combination with clinical information and/or additional biomarkers.
Biomarkers in Trypanosoma cruzi-Infected and Uninfected Individuals with Varying Severity of Cardiomyopathy in Santa Cruz, Bolivia

Background Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc−) individuals. Methods Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc− groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed. Results Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities. Conclusions BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.
The dynamics of response as measured by multiple composite outcome tools in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial

Background We aimed to evaluate the dynamics of treatment response with different composite measures in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. Methods Participants with early disease-modifying antirheumatic drug-naïve psoriatic arthritis (PsA) were randomised 1:1 to either tight control (TC; 4 weekly review with therapy escalation if criteria not met) or standard care (SC; 12 weekly review). We calculated modified versions of the Psoriatic ArthritiS Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite scorE (GRACE) and Composite Psoriatic Disease Activity Index (CPDAI) at baseline and 12 weekly to 48 weeks by blinded assessor. For missing data, we used the last observation carried forward. Comparison between groups was made by analysis of covariance and comparison of area under the curve (AUC). Results 206 people were randomised to TC (n=101) or SC (n=105). Significant differences between treatment groups were seen (p<0.0001 for all composite measures). AUC analysis demonstrated a significant difference between groups for the PASDAS but not GRACE and CPDAI. For participants with oligoarthritis, a significant difference between groups was seen for each measure, although the significance levels were greatly diminished (PASDAS, p=0.04; GRACE p=0.01; CPDAI p=0.04). For oligoarthritis using AUC analysis, none of the measures could distinguish between groups. Conclusions Composite measures of disease activity were able to distinguish between TICOPA treatment arms, although differences were diminished for those with oligoarthritis. Further data are needed to inform the preferred composite measure for use as the primary outcome in PsA trials. Trial registration number ClinicalTrials.gov (NCT01106079) and ISCRCTN registry (ISCRCTN30147736).
Gunshot Classification from Single-channel Audio Recordings using a Divide and Conquer Approach

Gunshot acoustic analysis is a field with many practical applications, but due to the multitude of factors involved in the generation of the acoustic signature of firearms, it is not a trivial task, especially since the recorded waveforms show a strong dependence on the shooterâs position and orientation, even when firing the same weapon. In this paper we address acoustic weapon classification using pattern recognition techniques with single channel recordings while taking into account the spatial aspect of the problem, so departing from the typical approach. We are working with three broad categories: rifles, handguns and shotguns. Our approach is based on two proposals: a Divide and Conquer classification strategy and the inclusion of some novel features based on the physical model of gunshot acoustics. The Divide and Conquer strategy is aimed at improving the rate of success of the classification stage by using previously retrieved spatial information to select between a set of specialized weapon classifiers. The minimum relative error reduction achieved when both proposals are used, compared with a single-stage classifier employing traditional features is 38.7%.
The new ACR/EULAR criteria for rheumatoid arthritis can identify patients with same disease activity but less damage by ultrasound.

OBJECTIVE We aimed to compare the ultrasound findings of patients fulfilling the 1987 ACR [OLD-rheumatoid arthritis (RA)] and the new ACR/EULAR (NEW-RA) classification criteria to examine the impact of the new criteria on disease characteristics, particularly disease duration. MATERIAL AND METHODS A total of 2730 hands, wrists, elbows, knees, ankles, and foot joints of 105 consecutive patients with inflammatory arthritis, i.e., 82 patients fulfilling the RA criteria (60 patients, OLD-RA; 22 patients, NEW-RA alone) and 23 patients with undifferentiated arthritis, were scanned using ultrasound. Synovitis, erosions, and power Doppler (PD) findings were scored using a scale of 0-3 and scores form each joint were added up to calculate synovitis, PD and erosion scores for each patient. RESULTS OLD-RA and NEW-RA patients had similar swollen joint count, tender joint count, acute-phase response, patient global, and disease activity assessment 28 scores. The disease duration was longer in OLD-RA patients [30 (3-179) months] than in NEW-RA patients [16 (0-45) months; p=0.009]. Both the groups had similar synovitis and PD scores, whereas erosion scores were higher in OLD-RA patients than in NEW-RA patients (p=0.009). Patients with undifferentiated arthritis were older than those with RA and had fewer swollen joints than NEW-RA patients [0 (0-4) vs. 2 (0-9); p=0.017]. All other disease activity parameters were similar in both NEW-RA and OLD-RA patients. Both the synovitis (p=0.006) and erosion (p=0.007) scores were lower in patients with undifferentiated arthritis than in OLD-RA patients, despite the scores being similar to those in NEW-RA patients. CONCLUSION The new ACR/EULAR RA criteria enabled the classification of patients with similar disease activity (by clinical assessment and ultrasound) but with less damage. A similar disease activity should ensure suitability for an intervention, and a shorter duration and less damage should improve the outcome with patient benefit.
An empirical method to cluster objective nebulizer adherence data among adults with cystic fibrosis

Background The purpose of using preventative inhaled treatments in cystic fibrosis is to improve health outcomes. Therefore, understanding the relationship between adherence to treatment and health outcome is crucial. Temporal variability, as well as absolute magnitude of adherence affects health outcomes, and there is likely to be a threshold effect in the relationship between adherence and outcomes. We therefore propose a pragmatic algorithm-based clustering method of objective nebulizer adherence data to better understand this relationship, and potentially, to guide clinical decisions. Methods to cluster adherence data This clustering method consists of three related steps. The first step is to split adherence data for the previous 12 months into four 3-monthly sections. The second step is to calculate mean adherence for each section and to score the section based on mean adherence. The third step is to aggregate the individual scores to determine the final cluster (“cluster 1” = very low adherence; “cluster 2” = low adherence; “cluster 3” = moderate adherence; “cluster 4” = high adherence), and taking into account adherence trend as represented by sequential individual scores. The individual scores should be displayed along with the final cluster for clinicians to fully understand the adherence data. Three illustrative cases We present three cases to illustrate the use of the proposed clustering method. Conclusion This pragmatic clustering method can deal with adherence data of variable duration (ie, can be used even if 12 months’ worth of data are unavailable) and can cluster adherence data in real time. Empirical support for some of the clustering parameters is not yet available, but the suggested classifications provide a structure to investigate parameters in future prospective datasets in which there are accurate measurements of nebulizer adherence and health outcomes.
T2*-Weighted MRI versus Oxygen Extraction Fraction PET in Acute Stroke

Background: Mapping high oxygen extraction fraction (OEF) in acute stroke is of considerable interest to depict the at-risk tissue. Being sensitive to deoxyhemoglobin, T2*-weighted MRI has been suggested as a potential marker of high OEF. Methods: We compared T2*-weighted images from pre-contrast arrival perfusion scans against quantitative positron emission tomography in 5 patients studied 7–21 h after onset of carotid territory stroke. OEF and T2* signal were obtained in the voxels with significantly high OEF. Results: All patients showed increased OEF. No significant relationship between OEF and T2*-weighted signal was found either within or between subjects. Conclusion: We found no indication that T2*-weighted MRI in the way implemented in this investigation was sensitive to high OEF in acute stroke.
Aerated drinks increase gastric volume and reduce appetite as assessed by MRI: a randomized, balanced, crossover trial.

BACKGROUND Compared with nonaerated, isocaloric controls, aerated foods can reduce appetite throughout an entire dieting day. Increased gastric volumes and delayed emptying are possible but unexplored mechanisms. OBJECTIVE We tested the hypothesis that aerated drinks (foams) of differing gastric stability would increase gastric distension and reduce appetite compared with a control drink. DESIGN In a randomized, balanced, crossover trial, 18 healthy male participants consumed the following 3 skimmed-milk-based test products (all 110 kcal): 2 drinks aerated to foams by whipping (to 490 mL), one drink that was stable in the stomach [stable foam (SF)], and one drink that was less stable in the stomach [less-stable foam (LSF)], and a nonaerated drink [liquid control (LC); 140 mL]. Over 4 h, stomach contents (foam, air, and liquid) were imaged using magnetic resonance imaging (MRI), and self-reported appetite ratings were collected and quantified by the area under the curve or time to return to baseline (TTRTB). RESULTS Compared with the LC, both foams caused significantly increased gastric volumes and reduced hunger (all P < 0.001). Compared with the LSF, SF further produced a significantly slower decrease in the total gastric content (P < 0.05) and foam volume (P < 0.0001) and a longer TTRTB (197 compared with 248 min, respectively; P < 0.05), although the hunger AUC was not statistically different. Results for other appetite scales were similar. CONCLUSIONS With this MRI trial, we provide novel insights on the gastrointestinal behavior of aerated drinks by measuring separate volumes of foam, liquid, and air layers in the stomach. Appetite suppression induced by foams could largely be explained by effects on gastric volumes and emptying, which may be further enhanced by foam stability. This trial was registered at clinicaltrials.gov as NCT01690182.
Epidemiology and Genetic Characterization of Noroviruses among Adults in an Endemic Setting, Peruvian Amazon Basin, 2004–2011

Background Successful vaccination strategies against norovirus will require understanding the burden of disease and relevant genotypes in populations. However, few data are available from cohort studies of adults living in low- and middle-income countries (LMIC). Materials and Methods We conducted a nested case-control study within a Peruvian military cohort to characterize the burden of norovirus infection, predominant genotypes, and associated symptoms from 2004 through 2011. Randomly selected case and control stools were tested for norovirus, bacteria, and parasites. The odds ratio of the association between norovirus infection and diarrhea was estimated using multiple logistic regression and co-infection adjusted attributable fractions were calculated. Results Of the 3,818 cohort study participants, 624 developed diarrhea. Overall and norovirus-associated diarrhea incidence rates were 42.3 and 6.0 per 100 person-years, respectively. The most prevalent norovirus genogroup was GII (72.5%, 29/40), which was associated with diarrhea (AOR 3.4, 95% CI: 1.3–8.7, P = 0.012). The co-infection adjusted GII attributable fraction was 6.4%. Discussion Norovirus was a frequent cause of diarrhea in an adult population followed longitudinally in an LMIC setting. Vaccine strategies should consider targeting adults in endemic settings and special populations that could serve as community transmission sources.
Early Signs of Osteoarthritis in Professional Ballet Dancers: A Preliminary Study

Objective:To investigate a cohort of professional ballet dancers for evidence of early signs of osteoarthritis (OA). Design:One radiologist and 1 orthopedic surgeon specialized in musculoskeletal disorders analyzed magnetic resonance imaging scans independently. Setting:University Teaching Hospital. Participants:Fifteen professional ballet dancers (4 males and 11 females; age range, 19-36 years) experiencing chronic pain in the hip, knee, spine, ankle, or foot joints. Main Outcome Measures:Presence of osteophytes, subchondral sclerosis, joint space narrowing, cysts, and bone marrow changes; the Kellgren and Lawrence scale was used to quantify the knee OA. Results:In the knee, there was thinning and irregularity of the articular cartilage over the medial femoral condyle and bone marrow changes within the lateral femoral condyle. In the hip, there was a loss of joint space and a frayed labrum with deep recess. The first metatarsophalangeal joint showed evidence of osteophytic development. Conclusions:Early signs of OA, in different joints, were present in a small but highly selected cohort of professional ballet dancers. In future, prospective studies among a number of ballet companies should control for medical and natural history alongside the visual analysis of images and plain radiographs to confirm these preliminary results.
The hypotensive effect of exercise on IOP : an interaction of physical fitness and parasympathetic efficacy

Purpose. Aerobic exercise is known to reduce elevated intraocular pressure (IOP), a primary risk factor for a disease of the eye known as Primary Open Angle Glaucoma (POAG). Given the disparate nature of experimental protocols across the literature an analysis of studies, on the effect of acute aerobic exercise on IOP, is necessary to verify the influence of participant characteristics, exercise intensity and duration. Method. The electronic databases PubMed, Web of Science and Embase were searched producing 35 empirical studies for review. Ten studies producing 14 independent groups were chosen as per the criteria of the analysis. Results. Random-effects models were used to produce subgroup analyses and metaregressions were used to verify the impact of group allocation, intensity and duration on the inter-study variability of the effect size. The outcome variable of post exercise change in IOP produced a significant effect of exercise, almost two-fold greater for sedentary populations than for normally active populations (ES = -4.198 [CI -5.151, -3.245], ES =-2.340 [CI -3.305, 1.375], respectively). Intensity and duration do not contribute to the overall effect size nor do they explain the difference between sedentary and normally active populations. Conclusions. There is a robust effect of exercise on IOP for sedentary participants. However, the heterogeneity across study parameters such as exercise protocol, IOP measurement and participant selection prohibited the inclusion of studies in this analysis that may have influenced the results. The current analysis makes clear the need for standardization of protocol across this field of research.
Vitamin D–Binding Protein Modifies the Vitamin D–Bone Mineral Density Relationship

Studies examining the relationship between total circulating 25‐hydroxyvitamin D [25(OH)D] levels and bone mineral density (BMD) have yielded mixed results. Vitamin D–binding protein (DBP), the major carrier protein for 25(OH)D, may alter the biologic activity of circulating vitamin D. We hypothesized that free and bioavailable 25(OH)D, calculated from total 25(OH)D, DBP, and serum albumin levels, would be more strongly associated with BMD than levels of total 25(OH)D. We measured total 25(OH)D, DBP, and serum albumin levels in 49 healthy young adults enrolled in the Metabolic Abnormalities in College‐Aged Students (MACS) study. Lumbar spine BMD was measured in all subjects using dual‐energy X‐ray absorptiometry. Clinical, diet, and laboratory information also was gathered at this time. We determined free and bioavailable (free + albumin‐bound) 25(OH)D using previously validated formulas and examined their associations with BMD. BMD was not associated with total 25(OH)D levels (r = 0.172, p = .236). In contrast, free and bioavailable 25(OH)D levels were positively correlated with BMD (r = 0.413, p = .003 for free, r = 0.441, p = .002 for bioavailable). Bioavailable 25(OH)D levels remained independently associated with BMD in multivariate regression models adjusting for age, sex, body mass index, and race (p = .03). It is concluded that free and bioavailable 25(OH)D are more strongly correlated with BMD than total 25(OH)D. These findings have important implications for vitamin D supplementation in vitamin D–deficient states. Future studies should continue to explore the relationship between free and bioavailable 25(OH)D and health outcomes. © 2011 American Society for Bone and Mineral Research.