Miracle-dz/UniFAR-FTUs huggingface dataset:
Contemporary antithrombotic strategies in patients with acute coronary syndrome admitted to cardiac care units in Italy: The EYESHOT Study

Background: Several new antithrombotic therapies have emerged for the treatment of acute coronary syndrome (ACS). We sought to assess contemporary patterns of antithrombotic therapies use in patients with ACS. Methods and results: EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in patients admitted to intensive cardiac care units (CCUs) for an ACS in Italy. Over a three-week period, 203 CCUs enrolled 2585 consecutive patients: 41.2% with ST-elevation myocardial infarction (STEMI) and 58.8% with non-ST elevation ACS (NSTE-ACS). During hospitalisation, low-molecular-weight heparins, aspirin, and clopidogrel were the most commonly used antithrombotic therapies. Among patients treated with percutaneous coronary intervention (PCI, n=1755), any crossover of heparin therapy occurred in 30.8% of cases, while switching from one P2Y12 inhibitor to another occurred in 3.6% of cases in the CathLab and in 14.2% before discharge. Of the 790 patients who did not receive revascularisation, switching of a P2Y12 inhibitor occurred in 5.7% of cases. At discharge, a new P2Y12 inhibitor (ticagrelor or prasugrel) in association with aspirin was prescribed in 59.5% of STEMI and 33.9% of NSTE-ACS patients: the most powerful predictor for prescription was PCI (odds ratio (OR) 6.18; 95% confidence interval (CI) 4.76–8.01; p<0.0001), whereas age ≥75 years was strongly associated with clopidogrel use (OR 0.28; 95% CI 0.22–0.36; p<0.0001). Conclusions: The EYESHOT registry shows the current pattern of antithrombotic treatments for ACS patients admitted to Italian CCUs and provides insights which may help to improve the clinical care of such patients.
Convergent Transcription through a Long CAG Tract Destabilizes Repeats and Induces Apoptosis

ABSTRACT Short repetitive sequences are common in the human genome, and many fall within transcription units. We have previously shown that transcription through CAG repeat tracts destabilizes them in a way that depends on transcription-coupled nucleotide excision repair and mismatch repair. Recent observations that antisense transcription accompanies sense transcription in many human genes led us to test the effects of antisense transcription on triplet repeat instability in human cells. Here, we report that simultaneous sense and antisense transcription (convergent transcription) initiated from two inducible promoters flanking a CAG95 tract in a nonessential gene enhances repeat instability synergistically, arrests the cell cycle, and causes massive cell death via apoptosis. Using chemical inhibitors and small interfering RNA (siRNA) knockdowns, we identified the ATR (ataxia-telangiectasia mutated [ATM] and Rad3 related) signaling pathway as a key mediator of this cellular response. RNA polymerase II, replication protein A (RPA), and components of the ATR signaling pathway accumulate at convergently transcribed repeat tracts, accompanied by phosphorylation of ATR, CHK1, and p53. Cell death depends on simultaneous sense and antisense transcription and is proportional to their relative levels, it requires the presence of the repeat tract, and it occurs in both proliferating and nonproliferating cells. Convergent transcription through a CAG repeat represents a novel mechanism for triggering a cellular stress response, one that is initiated by events at a single locus in the genome and resembles the response to DNA damage.
How to use D-dimer in acute cardiovascular care

D-dimer testing is important to aid in the exclusion of venous thromboembolic events (VTEs), including deep venous thrombosis and pulmonary embolism, and it may be used to evaluate suspected aortic dissection. D-dimer is produced upon activation of the coagulation system with the generation and subsequent degradation of cross-linked fibrin by plasmin. Many different assays for D-dimer testing are currently used in routine care. However, these tests are neither standardized nor harmonized. Consequently, only clinically validated assays and assay specific decision limits should be used for routine testing. For the exclusion of pulmonary embolism/deep vein thrombosis, age-adjusted cut-offs are recommend. Clinicians must be aware of the validated use of their hospital’s D-dimer assay to avoid inappropriate use of this biomarker in routine care.
Hopes and expectations of swedish cancer patients: Contradictions surrounding patient satisfaction with care

This paper presents a study of hopes and expectations concerning the professional health‐care sector, as expressed by a group of Swedish cancer patients. The data are derived from a cross‐sectional interview study of patients diagnosed with a malignant disease at one general hospital in Stockholm in 1987. A seeming discrepancy exists between the problematic situations and experiences described in narrative form by the participants, and the high rate of positive responses to direct questions concerned with satisfaction with care in this study. A combination of data types and an analytic process derived from medical anthropology has been utilized in order to understand the culturally related hopes and expectations which are behind statements of satisfaction with care. Hopes and expectations reflect the perceived breadth and limits of the professional health‐care sector. Patients appear to organize their experiences in manners which ‘work’. General dissatisfaction with care may not be an effective technique for promoting well‐being when diagnosed with a potentially life‐threatening disease. The patients in this study actively avoid dissatisfaction in a number of ways, which include assuming responsibility themselves, accepting the unarticulated as a form of discourse and adapting frameworks for that which is ‘normal’ from the professional sector.
Very fast detection for rate-2 quasi-orthogonal STBCs

For an important and standard rate-two quasi-orthogonal space-time block code, we propose a very fast detection scheme which achieves a wide range of tradeoff between performance and complexity. In the proposed scheme, exploiting the special quasi-orthogonal structure of the code, we efficiently obtain multiple candidate constellation points around the maximum likelihood (ML) point. Furthermore, we develop a very fast sorting method for the multiple candidate points to further improve the detection speed. Numerical results demonstrate that the proposed scheme can perform very close to the maximum likelihood detection at an extremely low complexity.
Research and implementation of DNSSEC monitoring system

DNS is one of internet infrastructure, but there also exist a lot of security vulnerabilities in it. The DNSSEC drafted by IETF is replacing the DNS for enhancing the security. However, the characteristics of DNSSEC have led to failure of the old monitoring system partly. This paper based on study of the DNSSEC protocol implementation and deployment proposes a kind of constructing plan about domain name redirecting, recursive domain name server record and national DLV trust chain. Then we establish an effective monitoring system. Finally, the feasibility of this plan has been verified in a simulated environment.
Systematic Analysis of Human Cells Lacking ATG8 Proteins Uncovers Roles for GABARAPs and the CCZ1/MON1 Regulator C18orf8/RMC1 in Macroautophagic and Selective Autophagic Flux

ABSTRACT Selective autophagy and macroautophagy sequester specific organelles/substrates or bulk cytoplasm, respectively, inside autophagosomes as cargo for delivery to lysosomes. The mammalian ATG8 orthologues (MAP1LC3A/B/C and GABARAP/L1/L2) are ubiquitin (UB)-like proteins conjugated to the autophagosome membrane and are thought to facilitate cargo receptor recruitment, vesicle maturation, and lysosomal fusion. To elucidate the molecular functions of the ATG8 proteins, we engineered cells lacking genes for each subfamily as well as all six mammalian ATG8s. Loss of GABARAPs alone attenuates autophagic flux basally and in response to macroautophagic or selective autophagic stimuli, including parkin-dependent mitophagy, and cells lacking all ATG8 proteins accumulate cytoplasmic UB aggregates, which are resolved following ectopic expression of individual GABARAPs. Autophagosomes from cells lacking GABARAPs had reduced lysosomal content by quantitative proteomics, consistent with fusion defects, but accumulated regulators of late endosome (LE)/autophagosome maturation. Through interaction proteomics of proteins accumulating in GABARAP/L1/L2-deficient cells, we identified C18orf8/RMC1 as a new subunit of the CCZ1-MON1 RAB7 guanine exchange factor (GEF) that positively regulates RAB7 recruitment to LE/autophagosomes. This work defines unique roles for GABARAP and LC3 subfamilies in macroautophagy and selective autophagy and demonstrates how analysis of autophagic machinery in the absence of flux can identify new regulatory circuits.
Deletion of Mtg16, a Target of t(16;21), Alters Hematopoietic Progenitor Cell Proliferation and Lineage Allocation

ABSTRACT While a number of DNA binding transcription factors have been identified that control hematopoietic cell fate decisions, only a limited number of transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and the nuclear hormone corepressor [N-CoR]) have been linked to these functions. Here, we show that the transcriptional corepressor Mtg16 (myeloid translocation gene on chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, is required for hematopoietic progenitor cell fate decisions and for early progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid progenitor cells toward the granulocytic/macrophage lineage while reducing the numbers of megakaryocyte-erythroid progenitor cells. In addition, inactivation of Mtg16 impaired the rapid expansion of short-term stem cells, multipotent progenitor cells, and megakaryocyte-erythroid progenitor cells that is required under hematopoietic stress/emergency. This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16−/− defect.
Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/β-Catenin Signaling

ABSTRACT Ubiquitination plays important and diverse roles in modulating protein functions. As a C2-WW-HECT-type ubiquitin ligase, Smad ubiquitination regulatory factor 1 (Smurf1) commonly serves to regulate ubiquitin-dependent protein degradation in a number of signaling pathways. Here, we report a novel function of Smurf1 in regulating Wnt/β-catenin signaling through targeting axin for nonproteolytic ubiquitination. Our data unambiguously demonstrate that Smurf1 ubiquitinates axin through Lys 29 (K29)-linked polyubiquitin chains. Unexpectedly, Smurf1-mediated axin ubiquitination does not lead to its degradation but instead disrupts its interaction with the Wnt coreceptors LRP5/6, which subsequently attenuates Wnt-stimulated LRP6 phosphorylation and represses Wnt/β-catenin signaling. The inhibitory function of Smurf1 on Wnt/β-catenin signaling is further evidenced by analysis with Smurf1 knockout murine embryonic fibroblasts. We next identified K789 and K821 in axin as the ubiquitination sites by Smurf1. Consistently, Smurf1 could neither disrupt the interaction of an axinK789/821R double mutant with LRP5/6 nor attenuate the phosphorylation of LRP6 in axinK789/821R-expressing cells. Collectively, our studies uncover Smurf1 as a new regulator for the Wnt/β-catenin signaling pathway via modulating the activity of axin.
Elevated HuR in Pancreas Promotes a Pancreatitis-Like Inflammatory Microenvironment That Facilitates Tumor Development

ABSTRACT Human antigen R (ELAVL1; HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes posttranscriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorigenesis is unknown and led us to explore the consequences of HuR overexpression using a novel transgenic mouse model that has a >2-fold elevation of pancreatic HuR expression. Histologically, HuR-overexpressing pancreas displays a fibroinflammatory response and other pathological features characteristic of chronic pancreatitis. This pathology is reflected in changes in the pancreatic gene expression profile due, in part, to genes whose expression changes as a consequence of direct binding of their respective mRNAs to HuR. Older mice develop pancreatic steatosis and severe glucose intolerance. Elevated HuR cooperated with mutant K-rasG12D to result in a 3.4-fold increase in pancreatic ductal adenocarcinoma (PDAC) incidence compared to PDAC presence in K-rasG12D alone. These findings implicate HuR as a facilitator of pancreatic tumorigenesis, especially in the setting of inflammation, and a novel therapeutic target for pancreatitis treatment.
Prevalence and characteristics of coronary microvascular dysfunction among chest pain patients in the emergency department

Aims: Coronary microvascular dysfunction (CMD) is common in patients with non-obstructive coronary arteries but has not been described in low-risk symptomatic patients. We therefore assessed the prevalence and characteristics of CMD in low to moderate risk patients with chest pain in an emergency department. Methods and results: We used three-dimensional Rb82 cardiac positron emission tomography/computed tomography to diagnose coronary artery disease (known or new regional defect, any coronary calcification) and CMD (low coronary flow reserve without coronary artery disease) in chest pain patients after being ruled out for acute myocardial infarction. Exclusions included age 30 years or less, acute myocardial infarction, hemodynamic instability, heart failure and dialysis. Among 195 participants undergoing cardiac positron emission tomography/computed tomography, 42% had CMD, 36% had coronary artery disease and 22% had normal flows; 70% were women and 84% were obese. Patients with CMD and coronary artery disease had significantly lower coronary flow reserve than normal patients (mean coronary flow reserve 1.6 and 1.9 vs. 2.6, respectively, P<0.05). However, CMD patients were younger (mean age 51 vs. 61 years), and had fewer traditional cardiac risk factors (P<0.05) than patients with coronary artery disease. Nearly one third (31%) of patients had a prior emergency department visit for chest pain within three years of index presentation. Women were four times as likely to have CMD as men (adjusted odds ratio 4.2; 95% confidence interval 1.8, 9.6) after controlling for age, race, hypertension, diabetes, smoking, dyslipidemia, obesity and family history of coronary artery disease. Conclusions: Despite their low-risk profile, nearly one half of symptomatic and mostly obese emergency department patients without evidence of myocardial infarction or coronary artery disease had CMD. The results could explain the high rates of return visits associated with chest pain, although their application to the general emergency department population require validation.
Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC

ABSTRACT Recognition of gene promoters by RNA polymerase II is mediated by general transcription factor IID (TFIID), which has been thought to be a static complex and to play a passive role in the regulation of gene expression under the instruction of gene-specific transcription factors. Here we show that transforming growth factor β (TGF-β) induced degradation of the TFIID subunit TAF7 in cultured mouse mammary epithelial cells and that this effect was required for proliferative arrest in response to TGF-β stimulation. TGF-β stimulated transcription of the gene for the ubiquitin ligase TRIM26, which was shown to ubiquitylate TAF7 and thereby to target it for proteasomal degradation. Sustained exposure of cells to TGF-β resulted in recovery from proliferative arrest in association with amplification of the Myc proto-oncogene, with MYC inhibiting TRIM26 induction by TGF-β. Our data thus show that TFIID is not simply a general mediator of transcription but contributes to the regulation of transcription in response to cell stimulation, playing a key role in the cytostatic function of TGF-β.
Recent Advancements in Temporomandibular Disorders (TMDs)

• TMDs are a group of conditions affecting the joint and or the muscles of mastication. • TMDs consist of three main groups of conditions: myofascial pain; disc disorders; TMJ arthritides. • The gold standard diagnostic criteria for research involving TMDs are the Research Diagnostic Criteria for TMDs (RDC/TMD). A pragmatic clinically applicable alternative is the Clinical examination protocol for TMDs (CEP-TMD). • Signs and symptoms can include: pain in masticatory musculature and or the joint; noises associated with joint movements; locking; headache; otalgia. • TMDs' aetiology is multifactorial and biopsychosocial in nature. • Reversible conservative management as defined by the American Association of Dental Research is the initial management of choice for all subgroups of TMDs.
Genetic Evidence of an Evolutionarily Conserved Role for Nrf2 in the Protection against Oxidative Stress

ABSTRACT Transcription factor Nrf2 is considered a master regulator of antioxidant defense in mammals. However, it is unclear whether this concept is applicable to nonmammalian vertebrates, because no animal model other than Nrf2 knockout mice has been generated to examine the effects of Nrf2 deficiency. Here, we characterized a recessive loss-of-function mutant of Nrf2 (nrf2fh318) in a lower vertebrate, the zebrafish (Danio rerio). In keeping with the findings in the mouse model, nrf2fh318 mutants exhibited reduced induction of the Nrf2 target genes in response to oxidative stress and electrophiles but were viable and fertile, and their embryos developed normally. The nrf2fh318 larvae displayed enhanced sensitivity to oxidative stress and electrophiles, especially peroxides, and pretreatment with an Nrf2-activating compound, sulforaphane, decreased peroxide-induced lethality in the wild type but not nrf2fh318 mutants, indicating that resistance to oxidative stress is highly dependent on Nrf2 functions. These results reveal an evolutionarily conserved role of vertebrate Nrf2 in protection against oxidative stress. Interestingly, there were no significant differences between wild-type and nrf2fh318 larvae with regard to their sensitivity to superoxide and singlet oxygen generators, suggesting that the importance of Nrf2 in oxidative stress protection varies based on the type of reactive oxygen species (ROS).
Hybrid Coherent/Energy Detection for Cognitive Radio Networks

Cognitive radio (CR) networks require reliable spectrum sensing in order to avoid interference to the primary users of the spectrum. Most existing spectrum sensing techniques are based on simple energy detection. However, in practice, the signals transmitted by primary users often also contain known pilot symbols for synchronization and channel estimation purposes. Coherent correlation based spectrum sensing techniques can exploit these known symbols but fail to utilize the energy contained in the data symbols. In this paper, we propose a hybrid coherent/energy detection scheme for spectrum sensing which exploits both the pilot and the data symbols transmitted by the primary user. Since the complexity of the globally optimal hybrid detection metric is very high, we develop a simple locally optimal hybrid metric, which turns out to be a linear combination of an energy detection metric and a correlation metric. We derive the probabilities of false alarm and missed detection of the proposed hybrid detector, and investigate the asymptotic behavior of both quantities for low signal-to-noise ratio and large sample size assuming that the CR network is optimized using a Neyman-Pearson framework. Simulation and analytical results confirm that the hybrid metric outperforms both energy detection and coherent detection even if the positions of the pilot symbols are not known a priori.
The Modelling of Injecting Behaviour and Initiation into Injecting

The modelling of injecting by injecting drug users (IDUs) around non-injecting drug users (NIDUs) is examined as a precursor to NIDUs initiation into injecting. Structured self-report interviews were conducted with 86 IDUs. 86% of the sample had been initiated into injecting by an IDU: 78% of their initiators being either a friend, partner, or sibling. Only 7% of respondents reported being pressured into injecting. 70% of respondents assessed that modelled injecting had been an important influence on their decision to inject by making them curious about injecting. In turn 98% of the respondents had modelled injecting around NIDUs, but 59% reported being unsure, or thought it unlikely, that they had made someone want to try injecting. Of these respondents 90% had talked to an NIDU about injecting, and 77% had injected around an NIDU. The findings suggest the need for interventions that raise awareness about the socially transmitted nature of injecting drug use.
Joint TOA and AOA Estimation for UWB Localization Applications

A joint TOA/AOA estimator is proposed for UWB indoor ranging under LOS operating conditions. The estimator employs an array of antennas, each feeding a demodulator consisting in a squarer and a low-pass filter. Signal samples taken at Nyquist rate at the filter outputs are processed to produce TOA and AOA estimates. Performance is assessed with transmitted pulses with a bandwidth of either 1.5 GHz (type-1 pulses) or 0.5 GHz (type-2 pulses), which correspond to sampling rates of 3 GHz and 1 GHz, respectively. As expected, the estimation accuracy decreases with the pulse bandwidth. Ranging errors of about 10 cm and angular errors of about 1° are achieved at SNR of practical interest with type-1 pulses and two antennas at a distance of 50 cm. With type-2 pulses the errors increase to 35 cm and 3°. Comparisons are made with other schemes discussed in literature.
Genome-Wide Profiling of Peroxisome Proliferator-Activated Receptor γ in Primary Epididymal, Inguinal, and Brown Adipocytes Reveals Depot-Selective Binding Correlated with Gene Expression

ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and function. We and others have previously mapped PPARγ binding at a genome-wide level in murine and human adipocyte cell lines and in primary human adipocytes. However, little is known about how binding patterns of PPARγ differ between brown and white adipocytes and among different types of white adipocytes. Here we have employed chromatin immunoprecipitation combined with deep sequencing to map and compare PPARγ binding in in vitro differentiated primary mouse adipocytes isolated from epididymal, inguinal, and brown adipose tissues. While these PPARγ binding profiles are overall similar, there are clear depot-selective binding sites. Most PPARγ binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPARγ binding sites that are specific to the primary cells, and these tend to be located in closed chromatin regions in 3T3-L1 adipocytes. The depot-selective binding of PPARγ is associated with highly depot-specific gene expression. This indicates that PPARγ plays a role in the induction of genes characteristic of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPARγ lineage-specific recruitment even when differentiated in vitro.