Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial

Abstract Aims The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). Methods and results In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of −9.6 mmHg (P = 0.01) and −13.5 mmHg (P = 0.0003) for systolic blood pressure and −5.2 mmHg (P = 0.02) and −8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (−0.24 vs. −0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up. Conclusion In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.
Efficacy and Safety of High Potent P2Y12 Inhibitors Prasugrel and Ticagrelor in Patients With Coronary Heart Disease Treated With Dual Antiplatelet Therapy: A Sex‐Specific Systematic Review and Meta‐Analysis

Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The aim of this study was to perform a sex‐specific analysis of the pooled efficacy and safety data of clinical trials comparing a high potent P2Y12 inhibitor+aspirin with clopidogrel+aspirin in patients with acute coronary syndrome. Methods and Results A systematic literature search was performed. Randomized clinical trials that compared patients following percutaneous coronary intervention/acute coronary syndrome who were taking high potent P2Y12 inhibitors+aspirin versus clopidogrel+aspirin were selected. Random effects estimates were calculated and relative risks with 95% CIs on efficacy and safety end points were determined per sex. We included 6 randomized clinical trials comparing prasugrel/ticagrelor versus clopidogrel in 43 990 patients (13 030 women), with a median follow‐up time of 1.06 years. Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80–1.00; men: RR, 0.84 [95% CI, 0.79–0.91) (P for interaction=0.39). Regarding safety, women and men had similar risk of major bleeding by high‐potency dual antiplatelet therapy (RR, 1.18 [95% CI, 0.98–1.41] versus RR, 1.03 [95% CI, 0.93–1.14]) (P for interaction=0.20). Conclusions The small and statistically insignificant difference in efficacy and safety estimates of high‐potency dual antiplatelet therapy between women and men following percutaneous coronary intervention/acute coronary syndrome do not justify differential dual antiplatelet therapy treatment for both sexes.
Glycerol-3-phosphate is a FGF23 regulator derived from the injured kidney.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin D3 [1,25(OH)2D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography-mass spectrometry-based (LC-MS-based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase-mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury.
"Lost Your Superpower"? Graphic Medicine, Voicelessness, and Georgia Webber's Dumb

abstract:Unlike deafness and disability, speech-related disorders—voluntary/involuntary voicelessness, mutism, and their imperatives—have largely remained undertheorized both as scholarship and praxis. Given the primacy and over-privileging of vision, a consideration of the nature of voice/voicelessness is critical and urgent. Framed in metaphysical, metaphorical, and existential terms, Georgia Webber's graphic memoir Dumb (2018), which narrates the protagonist's temporary loss of voice, is perhaps the first graphic medical text that coheres around issues related to voice/voicelessness in its entirety. Taking these cues, the present article, after briefly reviewing the significance of voice in human life and the relationship between voice and identity, provides a close reading of how Webber negotiates her lost acoustical agency in an otherwise abundant soundscape. Intriguingly, Webber also utilizes her voicelessness as a metaphor to reflect on her own marginality in an ableist society. Finally, the essay explores how Dumb projects drawing/comics-making and self-care as recuperative projects that not only help Webber to process her suffering caused by voicelessness but also aid her in reclaiming her lost voice and to acuminate practices of self-preservation.
Biomedical grafts for tracheal tissue repairing and regeneration “Tracheal tissue engineering: an overview”

Airway system is a vital part of the living being body. Trachea is the upper respiratory portion that connects nostril and lungs and has multiple functions such as breathing and entrapment of dust/pathogen particles. Tracheal reconstruction by artificial prosthesis, stents, and grafts are performed clinically for the repairing of damaged tissue. Although these (above‐mentioned) methods repair the damaged parts, they have limited applicability like small area wounds and lack of functional tissue regeneration. Tissue engineering helps to overcome the above‐mentioned problems by modifying the traditional used stents and grafts, not only repair but also regenerate the damaged area to functional tissue. Bioengineered tracheal replacements are biocompatible, nontoxic, porous, and having 3D biomimetic ultrastructure with good mechanical strength, which results in faster and better tissue regeneration. Till date, the bioengineered tracheal replacements studies have been going on preclinical and clinical levels. Besides that, still many researchers are working at advance level to make extracellular matrix‐based acellular, 3D printed, cell‐seeded grafts including living cells to overcome the demand of tissue or organ and making the ready to use tracheal reconstructs for clinical application. Thus, in this review, we summarized the tracheal tissue engineering aspects and their outcomes.
Distributional Validity and Prognostic Power of the National Institutes of Health Stroke Scale in US Administrative Claims Data.

Importance Comparative assessment of acute ischemic stroke care quality provided by hospitals in the United States has been hampered by the unavailability of the National Institutes of Health Stroke Scale (NIHSS) in administrative data sets, preventing adequate adjustment for variations in patient case-mix risk. In response to stakeholder concerns, the US Centers for Medicare & Medicaid Services in 2016 implemented optional reporting of NIHSS scores. Objective To analyze the distributional, convergent, and predictive validity of nationally submitted NIHSS values in the National Inpatient Sample. Design, Setting, and Participants This population-based retrospective cross-sectional study took place from October 1 to December 31, 2016. The nationally representative sample included US adults who had ischemic stroke hospitalizations during the first calendar quarter in which optional NIHSS reporting was implemented. Analysis began September 2019. Main Outcomes and Measures Distribution of NIHSS scores, functional independence at discharge, inpatient mortality, and administrative reporting of NIHSS. Results Among 154 165 ischemic stroke hospitalizations during the first 3 months of the reporting policy, NIHSS scores were reported in 21 685 patients (14%) (10 925 women [50.4%]; median [interquartile range] age, 72 [61-82] years). Median (interquartile range) NIHSS score was 4 (2-11), and frequency of severity categories included absent (NIHSS score, 0) in 2080 patients (9.6%), minor (NIHSS score, 1-4) in 8760 patients (40.4%), and severe (NIHSS score, 21-42) in 1930 patients (8.9%). National Institutes of Health Stroke Scale score of 10 or more, an indicator of possible large vessel occlusions, was present in 6290 patients (29%). Presenting NIHSS score was higher in very elderly patients (age ≥80 y) and women and also in patients receiving endovascular thrombectomy vs intravenous thrombolysis alone vs no reperfusion therapy (median [interquartile range], 17 [12-22] vs 6 [4-12] vs 4 [2-9], respectively) (P < .001). National Institutes of Health Stroke Scale scores were similarly higher for discharge outcomes of mortality vs discharge to skilled nursing facility vs discharge home (median [interquartile range], 19 [12-25] vs 7 [3-15] vs 2 [1-5], respectively) (P < .001). Likelihood of NIHSS scores being reported independently increased with interfacility transfer, receipt of acute reperfusion therapies, larger hospital size, academic centers, and region other than the West. Conclusions and Relevance In the initial national optional reporting period in the United States, NIHSS scores were reported in nearly 1 in 7 ischemic stroke hospitalizations. The distribution of NIHSS scores was similar to that from narrow population-based studies and registries, and NIHSS scores were powerfully associated with discharge outcome, supporting the validity and potential to aid care quality assessment.
A computational platform to identify origins of replication sites in eukaryotes

The locations of the initiation of genomic DNA replication are defined as origins of replication sites (ORIs), which regulate the onset of DNA replication and play significant roles in the DNA replication process. The study of ORIs is essential for understanding the cell-division cycle and gene expression regulation. Accurate identification of ORIs will provide important clues for DNA replication research and drug development by developing computational methods. In this paper, the first integrated predictor named iORI-Euk was built to identify ORIs in multiple eukaryotes and multiple cell types. In the predictor, seven eukaryotic (Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana, Pichia pastoris, Schizosaccharomyces pombe and Kluyveromyces lactis) ORI data was collected from public database to construct benchmark datasets. Subsequently, three feature extraction strategies which are k-mer, binary encoding and combination of k-mer and binary were used to formulate DNA sequence samples. We also compared the different classification algorithms' performance. As a result, the best results were obtained by using support vector machine in 5-fold cross-validation test and independent dataset test. Based on the optimal model, an online web server called iORI-Euk (http://lin-group.cn/server/iORI-Euk/) was established for the novel ORI identification.
The Wheat 660K SNP array demonstrates great potential for marker‐assisted selection in polyploid wheat

Abstract The rapid development and application of molecular marker assays have facilitated genomic selection and genome‐wide linkage and association studies in wheat breeding. Although PCR‐based markers (e.g. simple sequence repeats and functional markers) and genotyping by sequencing have contributed greatly to gene discovery and marker‐assisted selection, the release of a more accurate and complete bread wheat reference genome has resulted in the design of single‐nucleotide polymorphism (SNP) arrays based on different densities or application targets. Here, we evaluated seven types of wheat SNP arrays in terms of their SNP number, distribution, density, associated genes, heterozygosity and application. The results suggested that the Wheat 660K SNP array contained the highest percentage (99.05%) of genome‐specific SNPs with reliable physical positions. SNP density analysis indicated that the SNPs were almost evenly distributed across the whole genome. In addition, 229 266 SNPs in the Wheat 660K SNP array were located in 66 834 annotated gene or promoter intervals. The annotated genes revealed by the Wheat 660K SNP array almost covered all genes revealed by the Wheat 35K (97.44%), 55K (99.73%), 90K (86.9%) and 820K (85.3%) SNP arrays. Therefore, the Wheat 660K SNP array could act as a substitute for other 6 arrays and shows promise for a wide range of possible applications. In summary, the Wheat 660K SNP array is reliable and cost‐effective and may be the best choice for targeted genotyping and marker‐assisted selection in wheat genetic improvement.
Expression of 22 serotonin-related genes in rat brain after sub-acute serotonin depletion or reuptake inhibition

Abstract Objective: Although the assessment of expression of serotonin-related genes in experimental animals has become a common strategy to shed light on variations in brain serotonergic function, it remains largely unknown to what extent the manipulation of serotonin levels causes detectable changes in gene expression. We therefore chose to investigate how sub-acute depletion or elevation of brain serotonin influences the expression of a number of serotonin-related genes in six brain areas. Methods: Male Wistar rats were administered a serotonin synthesis inhibitor, para-chlorophenylalanine (p-CPA), or a serotonin reuptake inhibitor, paroxetine, for 3 days and then sacrificed. The expression of a number of serotonin-related genes in the raphe nuclei, hypothalamus, amygdala, striatum, hippocampus and prefrontal cortex was investigated using real-time quantitative PCR (rt-qPCR). Results: While most of the studied genes were uninfluenced by paroxetine treatment, we could observe a robust downregulation of tryptophan hydroxylase-2 in the brain region where the serotonergic cell bodies reside, that is, the raphe nuclei. p-CPA induced a significant increase in the expression of Htr1b and Htr2a in amygdala and of Htr2c in the striatum and a marked reduction in the expression of Htr6 in prefrontal cortex; it also enhanced the expression of the brain-derived neurotrophic factor (Bdnf) in raphe and hippocampus. Conclusion: With some notable exceptions, the expression of most of the studied genes is left unchanged by short-term modulation of extracellular levels of serotonin.
Sublingual microcirculation in Prehospital Critical Care Medicine - a Proof of Concept Study.

OBJECTIVE Diagnostic and risk stratification are limited in emergencies. The measurement of microcirculation might identify patients with poor perfusion but compensated macrocirculation such as in beginning shock. This proof-of-concept study examines whether sublingual prehospital sidestream dark field microscopy is feasible. METHODS This prospective observational study included patients receiving medical aid by an emergency ambulance who had a spontaneous circulation and offered access to the sublingual mucosa. Sublingual measurement of microcirculation was performed using a sidestream dark field camera. Video-quality was evaluated with MIQS (microcirculation image quality score). AVA 4.3C software calculated microcirculatory parameters. RESULTS Thirty patients (47% male) were included. The average age was 63 years (± 20 years SD), the severity of the disease (quantified by NACA) was 3.4 (± 0.7 SD). Macrocirculation presented within the normal range. The most frequent cause preventing the measurement was a time-critical disease (64%). In 17 patients (57%), the videos could be analyzed immediately. The average quality of the video was 2.2 ± 0.45 points ("acceptable"). There were minor restrictions of microcirculation. Microcirculation correlated with NACA, but not with the macrocirculation. No complications occurred. CONCLUSION The prehospital sublingual measurement is safe and valid. Despite normal macrocirculation, microcirculation was impaired and correlated with NACA.
This paper is included in the Proceedings of the 18th USENIX Conference on File and Storage Technologies (FAST ’20)

Persistent key-value stores are widely used as building blocks in today’s IT infrastructure for managing and storing large amounts of data. However, studies of characterizing real-world workloads for key-value stores are limited due to the lack of tracing/analyzing tools and the difﬁculty of collecting traces in operational environments. In this paper, we ﬁrst present a detailed characterization of workloads from three typical RocksDB production use cases at Facebook: UDB (a MySQL storage layer for social graph data), ZippyDB (a distributed key-value store), and UP2X (a distributed key-value store for AI/ML services). These characterizations reveal several interesting ﬁndings: ﬁrst, that the distribution of key and value sizes are highly related to the use cases/applications; second, that the accesses to key-value pairs have a good locality and follow certain special patterns; and third, that the collected performance metrics show a strong diurnal pattern in the UDB, but not the other two. We further discover that although the widely used key-value benchmark YCSB provides various workload conﬁgurations and key-value pair access distribution models, the YCSB-triggered workloads for underlying storage systems are still not close enough to the workloads we collected due to ig-norance of key-space localities. To address this issue, we propose a key-range based modeling and develop a benchmark that can better emulate the workloads of real-world key-value stores. This benchmark can synthetically generate more precise key-value queries that represent the reads and writes of key-value stores to the underlying storage system.
Psychometric validation of the Turkish Ten-Item Internet Gaming Disorder Test (IGDT-10)

1Bakirkoy Training and Research Hospital for Psychiatry Neurology and Neurosurgery, Research, Treatment and Training Center for Alcohol and Substance Dependence (AMATEM), Istanbul Turkey 2Baltalimani State Hospital for Musculoskeletal Disorders, Department of Psychiatry, Istanbul Turkey 3Yuksek Ihtisas University, Faculty of Medicine, Department of Psychiatry, Ankara Turkey 4Cankaya University, Department of Psychology, Ankara Turkey
The Effect of Hospital Competition on Value-Added Indicators of Elective Surgery Quality∗

There is increasing international interest in using Patient Reported Outcome Measures (PROMs) to assess health care provider performance. PROMs are a fundamental advance on existing indicators of health care quality in two respects: they equate outcomes with value added (i.e. health gain) from treatment rather than post-treatment health status, and they allow clinical quality to be measured at the level of the individual medical intervention to a far greater extent than existing failure-based indicators such as mortality or readmissions. Most existing econometric studies of hospital competition and quality equate outcomes with post-treatment health status, and use mortality rates of various kinds as indicators of overall hospital performance, in spite of the fact that mortality is a relatively uncommon outcome in the spheres of hospital activity – such as elective surgery – in which competition for patients does occur. This paper contributes to the development of a value-added, multi-product conception of hospital quality by studying the impact of a major competition-promoting reform to the English NHS in 2006, in which patients were allowed to choose which hospital they attended for elective surgery, on PROMs of health gain from hip and knee replacement surgery. In contrast to the existing literature, I find that the competition brought about by the introduction of patient choice of hospital appears to have had a negative effect on clinical quality in some areas of hospital activity. I hypothesise that this effect occurred because of differences in the observability and salience of quality across areas of hospital activity.
A Low-Profile Wideband Antenna for WWAN/LTE Applications

In this paper, a low-profile antenna is presented for wideband communication applications. The presented design consists of an I-shaped driven strip and a rectangular ground strip with an open slot in the middle and a steeped lower portion. The measured results demonstrate that the achieved operating band of the proposed antenna has the potential to cover Globalstar satellite phones (GSSP) (1.61–1.63 GHz, uplink), advanced wireless systems (1.71–1.76 GHz, 2.11–2.17 GHz), DCS (1710–1880 MHz), GSM (1800MHz), DCP (1.88–1.90 GHz), DCS-1900/PCS/PHS (1850–1990MHz), WCDMA/IMT-2000 (1920–2170MHz), UMTS (1920–2170 MHz) and long-term evolution (LTE) bands (FDD LTE bands 1–4, 9–10, 15–16, 23–25, 33–37, 39). The designed antenna possessed a very small size of 0. 35λ0 × 0. 027λ0 at the lowest frequency (S11 ≤ −10dB), achieved good gains and exhibited stable radiation patterns, which makes it suitable for handheld communication devices.
JOAN BAPTISTA VAN HELMONT AND THE QUESTION OF EXPERIMENTAL MODERNISM

In this paper, I take up the question to what extent and in which sense we can conceive of Joan Baptista Van Helmont’s (1579-1644) style of experimenting as ‘‘modern. ’’ Connected to this question, I shall reflect upon what Van Helmont’s precise contribution to experimental practice has been. I will argue – after having analysed some of Van Helmont’s experiments such as his tree experiment, ice experiment, and thermoscope experiment – that Van Helmont had a strong preference to locate experimental designs in places wherein variables can be more easily controlled (and, ultimately, in relatively closed physical systems such as, paradigmatically, the vessel, globe, or sphere [vas, globus, sphera]). After having reviewed some alternative options, I shall argue that Van Helmont’s usage of relatively isolated physical systems and a moderate degree of quantification is the feature that best characterizes his contributions to ‘‘modern’’ experimentation.