Miracle-dz/UniFAR-FTUs huggingface dataset:
Which Factors Are Associated with the Application of Reperfusion Therapy in ST-Elevation Acute Coronary Syndromes?

Background/Aims:A large proportion of patients with a ST-elevation acute coronary syndrome do not receive reperfusion therapy. In order to contribute to a better understanding of the clinical decision making process, we analyzed which factors are associated with the application of reperfusion therapy. Methods: From the Euro Heart Survey of Acute Coronary Syndromes I, 4,260 patients with ST-elevation acute coronary syndrome were selected for the current analysis, of which 1,539 (36%) patients received fibrinolysis and 904 (21%) primary percutaneous coronary intervention (PCI). The analysis contained 32 variables on demographics, medical history, admission parameters and reperfusion therapy. Results: A short pre-hospital delay, arrival in a hospital with PCI facilities, severe ST-elevation, and participation in a clinical trial were the strongest predictors for receiving reperfusion therapy. Primary PCI was more likely to be performed than fibrinolysis in patients with a long pre-hospital delay, arriving in a hospital with PCI facilities, not participating in a clinical trial, and with at least one previous PCI. Conclusion:Hospital facilities and culture, pre-hospital delay and infarction size play a major role in management decisions regarding reperfusion therapy in ST-elevation acute coronary syndrome. This analysis indicates which factors require special attention when implementing and reviewing the reperfusion guidelines.
Structural Characterization of the Cell Division Cycle in Strigomonas culicis, an Endosymbiont-Bearing Trypanosomatid

Abstract Strigomonas culicis (previously referred to as Blastocrithidia culicis) is a monoxenic trypanosomatid harboring a symbiotic bacterium, which maintains an obligatory relationship with the host protozoan. Investigations of the cell cycle in symbiont harboring trypanosomatids suggest that the bacterium divides in coordination with other host cell structures, particularly the nucleus. In this study we used light and electron microscopy followed by three-dimensional reconstruction to characterize the symbiont division during the cell cycle of S. culicis. We observed that during this process, the symbiotic bacterium presents different forms and is found at different positions in relationship to the host cell structures. At the G1/S phase of the protozoan cell cycle, the endosymbiont exhibits a constricted form that appears to elongate, resulting in the bacterium division, which occurs before kinetoplast and nucleus segregation. During cytokinesis, the symbionts are positioned close to each nucleus to ensure that each daughter cell will inherit a single copy of the bacterium. These observations indicated that the association of the bacterium with the protozoan nucleus coordinates the cell cycle in both organisms.
[Standardized sweat chloride analysis for the diagnosis of cystic fibrosis in Korea].

BACKGROUND Cystic fibrosis is a chronic progressive autosomal recessive disorder caused by the CFTR gene mutations. It is quite common in Caucasians, but very rare in Asians. Sweat chloride test is known to be a screening test for the cystic fibrosis due to the fact that electrolyte levels in sweat are elevated in patients. In this study, sweat chloride levels in Korean population were measured and analyzed by using standardized pilocarpine iontophoresis sweat chloride test. METHODS The sweat chloride test was performed in 47 patients referred to Yondong Severance Hospital from August, 2001 to April, 2007 and 41 healthy volunteers. The sweat chloride tests were conducted according to the CLSI C34-A2 guideline using pilocarpine iontophoresis method, and the chloride concentrations in sweat were measured by mercurimetric titration. RESULTS Four patients showed sweat chloride concentrations higher than 60 mmol/L. Reference interval was calculated as 1.4-44.5 mmol/L by analysis of the results of healthy volunteers (n=41). Four patients who exhibited high sweat chloride levels, had characteristic clinical features of cystic fibrosis and their diagnoses were confirmed either by repeated sweat chloride test or genetic analysis. CONCLUSIONS Standardized sweat chloride test can be utilized as a useful diagnostic tool for cystic fibrosis in Koreans. In cases of sweat chloride levels higher than 40 mmol/L, the test should be repeated for the possible diagnosis of cystic fibrosis. All the confirmed Korean cases of cystic fibrosis showed sweat chloride level above 60 mmol/L.
Does Timing of Orphanhood and HIV Prevalence Matter ? A Look at Orphans ’ Transitions to Sexual Debut and Marriage in Four Sub-Saharan African Countries

Debate exists as to whether orphaned adolescents are more vulnerable than their non-orphaned peers to early sexual debut and marriage. I revisit this question by using data from the National Survey of Adolescents 2004, which targets adolescents, 12-19 years, in Burkina Faso, Ghana, Malawi, and Uganda. Contrary to previous studies, I explore whether timing of orphanhood and HIV prevalence matters. I also hypothesize that educational differences may explain orphans’ greater risk of these outcomes. Results indicate that female double orphans are vulnerable to early sexual debut; however, male orphans, of any type, are not at increased risk. Education explains very little, if any, of female double orphans’ greater vulnerability. While female orphans are not more likely to marry early in three out of four countries, those who became paternal and double orphans before age 10 are more likely to marry in Uganda. Education explains some portion of this increased risk. 1 Sophia Chae, Graduate Student in Demography, University of Pennsylvania, 239 McNeil Building, 3718 Locust Walk, Philadelphia, PA, 19104-6298. Email: sochae@sas.upenn. edu
Persistence of side population cells with high drug efflux capacity in pancreatic cancer.

AIM To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance. METHODS The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine, was detected by Hoechst 33342 staining and FACS analysis. The expression of ABCB1 and ABCG2 was detected by real-time PCR in either SP cells or non-SP cells. RESULTS SP cells do exist in PANC-1, with a median of 3.3% and a range of 2.1-8.7%. After cultured with Gemcitabine for 3 d, the proportion of SP cells increased significantly (3.8% +/- 1.9%, 10.7% +/- 3.7%, t = 4.616, P = 0.001 < 0.05). ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCB1: 1.15 +/- 0.72, 5.82 +/- 1.16, t = 10.839, P = 0.000 < 0.05; ABCG2: 1.16 +/- 0.75, 5.48 +/- 0.94, t = 11.305, P = 0.000 < 0.05), which may contribute to the efflux of fluorescent staining and drug resistance. CONCLUSION SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers, which may be candidate cancer stem cells contributing to the relapse of the tumor.
Fibroblast Growth Factor-10

Fibroblast growth factor (FGF)-10, a homologue of FGF-7, is expressed significantly in normal rat prostate tissue, well differentiated rat prostate tumors with an epithelial and stromal compartment and only in derived prostate stromal cells in culture. Similar to FGF-7, recombinant rat FGF-10 was a specific mitogen for prostate epithelial cells. In contrast to FGF-7 which is widely expressed among stromal cells in tissues, the expression of FGF-10 correlated with the presence of stromal cells of muscle origin. Radioreceptor binding assays and covalent cross-linking analysis revealed that FGF-10 binds with an affinity equal to FGF-7 to resident epithelial cell receptor, FGFR2IIIb, but unlike FGF-7 also binds the IIIb splice variant of FGFR1. Analysis of mRNA expression by RNase protection revealed that, similar to FGF-7, the expression of FGF-10 was responsive to androgen in stromal cells from normal prostate and non-malignant differentiated tumors. Although FGF-10 cDNA exhibits a signal sequence for secretion, cultured stromal cells exhibit strictly a cell-associated FGF-10 antigen that correlates with an alternately translated intracellular isoform. FGF-10 requires 1.4 times higher NaCl for elution from immobilized heparin than does FGF-7 and binds to four times the number of sites on the pericellular matrix of epithelial cells. The results show that prostate stromal cell-derived FGF-10, like FGF-7, exhibits the properties of an andromedin which may indirectly mediate control of epithelial cell growth and function by androgen. Although FGF-10 and FGF-7 bind and activate the same resident epithelial cell receptor (FGFR2IIIb), differences in cell type of origin, compartmentation by alternate translation, the affinity for FGFR1IIIb, and access to FGFR by differential interaction with pericellular matrix heparan sulfate suggest they may play both independent and compensatory roles in prostate homeostasis.
Robust Clustering Using Exponential Power Mixtures

Summary Clustering is a widely used method in extracting useful information from gene expression data, where unknown correlation structures in genes are believed to persist even after normalization. Such correlation structures pose a great challenge on the conventional clustering methods, such as the Gaussian mixture (GM) model, k‐means (KM), and partitioning around medoids (PAM), which are not robust against general dependence within data. Here we use the exponential power mixture model to increase the robustness of clustering against general dependence and nonnormality of the data. An expectation–conditional maximization algorithm is developed to calculate the maximum likelihood estimators (MLEs) of the unknown parameters in these mixtures. The Bayesian information criterion is then employed to determine the numbers of components of the mixture. The MLEs are shown to be consistent under sparse dependence. Our numerical results indicate that the proposed procedure outperforms GM, KM, and PAM when there are strong correlations or non‐Gaussian components in the data.
Techniques for risk stratification of newly diagnosed patients with chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by BCR–ABL, a constitutively active tyrosine kinase generated as a result of the t(9;22)(q34;q11). The natural history of CML is progression from a relatively benign chronic phase to an acute leukemia termed blast crisis. Imatinib, an inhibitor of BCR–ABL tyrosine kinase activity, has a dramatic effect on the natural history of the disease. Despite the favorable outcomes with imatinib, a subset of patients have primary refractory disease, or experience relapse after an initial response. Recently identified molecular predictors of drug response might help predict outcome with tyrosine kinase inhibitor therapy more accurately than clinical prognostication scores, but have not yet been introduced into clinical routine. These techniques include analysis of drug transport proteins, in vitro drug assays, measurement of imatinib plasma levels, BCR–ABL activity monitoring, and gene expression profiling. In this article we review the current status of these technologies, which may ultimately allow us to tailor therapy to a specific patient.
CD22 Ligand Binding Regulates Normal and Malignant B Lymphocyte Survival In Vivo1

The CD22 extracellular domain regulates B lymphocyte function by interacting with α2,6-linked sialic acid-bearing ligands. To understand how CD22 ligand interactions affect B cell function in vivo, mouse anti-mouse CD22 mAbs were generated that inhibit CD22 ligand binding to varying degrees. Remarkably, mAbs which blocked CD22 ligand binding accelerated mature B cell turnover by 2- to 4-fold in blood, spleen, and lymph nodes. CD22 ligand-blocking mAbs also inhibited the survival of adoptively transferred normal (73–88%) and malignant (90%) B cells in vivo. Moreover, mAbs that bound CD22 ligand binding domains induced significant CD22 internalization, depleted marginal zone B cells (82–99%), and reduced mature recirculating B cell numbers by 75–85%. The CD22 mAb effects were independent of complement and FcRs, and the CD22 mAbs had minimal effects in CD22AA mice that express mutated CD22 that is not capable of ligand binding. These data demonstrate that inhibition of CD22 ligand binding can disrupt normal and malignant B cell survival in vivo and suggest a novel mechanism of action for therapeutics targeting CD22 ligand binding domains.
Childhood Trauma and Posttraumatic Stress Disorder in Substance Abuse Inpatients

This pilot study examined: the prevalence of childhood trauma in a sample of male veteran substance abuse inpatients, and the relationship of childhood trauma to substance abuse in this sample, controlling for posttraumatic stress disorder (PTSD). Forty-six subjects were interviewed using the Traumatic Antecedents Questionnaire, Structured Clinical Interview for DSM-III-R (SCID)-P Psychoactive Substance Use Disorders module, the Addiction Severity Index, and the SCID-NP-V PTSD module. Seventy-seven percent of subjects had been exposed to severe childhood trauma. Fifty-eight percent had lifetime PTSD. The total number of lifetime substance dependence disorders was strongly positively associated with total childhood trauma exposure. This relationship remained significant after controlling for demographics, family history of alcohol problems, combat exposure, and lifetime PTSD, including combat-related PTSD. A substantial number of these subjects reported exposure to childhood trauma, which in turn was related to multiple substance dependence. This has important implications for the natural history and prevention of multiple substance dependence disorders.
mTORC2/Rictor Signaling Disrupts Dopamine-Dependent Behaviors via Defects in Striatal Dopamine Neurotransmission

Disrupted neuronal protein kinase B (Akt) signaling has been associated with dopamine (DA)-related neuropsychiatric disorders, including schizophrenia, a devastating mental illness. We hypothesize that proper DA neurotransmission is therefore dependent upon intact neuronal Akt function. Akt is activated by phosphorylation of two key residues: Thr308 and Ser473. Blunted Akt phosphorylation at Ser473 (pAkt-473) has been observed in lymphocytes and postmortem brains of schizophrenia patients, and psychosis-prone normal individuals. Mammalian target of rapamycin (mTOR) complex 2 (mTORC2) is a multiprotein complex that is responsible for phosphorylation of Akt at Ser473 (pAkt-473). We demonstrate that mice with disrupted mTORC2 signaling in brain exhibit altered striatal DA-dependent behaviors, such as increased basal locomotion, stereotypic counts, and exaggerated response to the psychomotor effects of amphetamine (AMPH). Combining in vivo and ex vivo pharmacological, electrophysiological, and biochemical techniques, we demonstrate that the changes in striatal DA neurotransmission and associated behaviors are caused, at least in part, by elevated D2 DA receptor (D2R) expression and upregulated ERK1/2 activation. Haloperidol, a typical antipsychotic and D2R blocker, reduced AMPH hypersensitivity and elevated pERK1/2 to the levels of control animals. By viral gene delivery, we downregulated mTORC2 solely in the dorsal striatum of adult wild-type mice, demonstrating that striatal mTORC2 regulates AMPH-stimulated behaviors. Our findings implicate mTORC2 signaling as a novel pathway regulating striatal DA tone and D2R signaling.
Curcuminoids distinctly exhibit antioxidant activities and regulate expression of scavenger receptors and heme oxygenase-1.

SCOPE Curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) have been demonstrated as having antioxidant, anticarcinogenic, and hypocholesterolemic activities. We report the diverse antiatherogenic effects and mechanisms of curcuminoids. METHODS AND RESULTS We found that CUR was the most potent antioxidant against copper-mediated LDL oxidation as measured by thiobarbituric acid-reactive substances assay, oxidized LDL (oxLDL) ELISA, and electrophoretic mobility. CUR upregulated heme oxygenase-1, modifier subunit of glutamate-cysteine ligase (GCLM), and CD36 expression in undifferentiated THP-1 cells, supporting the possible involvement of Nrf2 pathway in CD36 expression. Monocyte-to-macrophage differentiation plays a vital role in early atherogenesis. BDMC reduced oxLDL uptake most effectively, while CUR was the best inhibitor for CD36, scavenger receptor A, and lectin-like oxidized LDL receptor-1 expression during phorbol 12-myristate 13-acetate (PMA)-induced THP-1 differentiation. In PMA-differentiated THP-1 macrophages, CUR and DMC effectively induced heme oxygenase-1 expression, but attenuated oxLDL-induced CD36 expression, leading to decreased oxLDL uptake. CONCLUSION This result indicates curcuminoids, despite structural similarities, exert different atheroprotective effects. Curcuminoids, especially CUR and DMC, are hormetic compounds, which induce Phase II enzyme expression and confer resistance to PMA- and oxLDL-induced scavenger receptor expression and activity.
The Effects of Values and Costs on the Detection and Identification of Signals in Auditory Vigilance1

The effects on performance of the value of detecting a signal, the cost of a miss or false detection, and the size of the set from which the signals were drawn were studied in an auditory vigilance task. Seventy-two subjects were randomly assigned to each cell of a factorial arrangement of the cost and load variables and required to detect and identify each of several 49 db SPL pure tones differing only in frequency. Analyses of the number of correct detections, correct identifications, false detections and detection response time indicated a significant performance decrement with time for all measures and suggested that increasing costs for misses and false detections led to poorer detection performance while value had no effect. Load effected only identification performance, as higher loads led to a decrease in the percentage of signals correctly identified. The ď and β statistics of signal detection theory, indicated sensitivity to be invariant with manipulations of costs and with time. These findings imply that the performance decrement during a vigil is due to an increased strictness in the criterion the subject sets for deciding whether or not a signal was present. The cost factors were effective in manipulating performance by causing changes in the subjects' decision criteria.
DISCOVERY OF COHERENT PULSATIONS FROM THE ULTRALUMINOUS X-RAY SOURCE NGC 7793 P13

We report the detection of coherent pulsations from the ultraluminous X-ray source (ULX) NGC 7793 P13. The ≈0.42 s nearly sinusoidal pulsations were initially discovered in broadband X-ray observations using XMM-Newton and NuSTAR taken in 2016. We subsequently also found pulsations in archival XMM-Newton data taken in 2013 and 2014. The significant (≫5σ) detection of coherent pulsations demonstrates that the compact object in P13 is a neutron star, and given the observed peak luminosity of ≈1040 erg s − 1 (assuming isotropy), it is well above the Eddington limit for a 1.4 M ⊙ accretor. This makes P13 the second ULX known to be powered by an accreting neutron star. The pulse period varies between epochs, with a slow but persistent spin-up over the 2013–2016 period. This spin-up indicates a magnetic field of B ≈ 1.5 × 1012 G, typical of many Galactic accreting pulsars. The most likely explanation for the extreme luminosity is a high degree of beaming; however, this is difficult to reconcile with the sinusoidal pulse profile.
Long-term follow-up and risk assessment of arrhythmogenic right ventricular dysplasia/cardiomyopathy: personal experience from different primary and tertiary centres

Objectives Limited data are available on the course of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) because of the low frequency of this diagnosis. A long-term follow-up was analysed in typical ARVD/C patients from different primary and tertiary centres, and risk factors for sudden cardiac death (SCD) and end-stage heart failure were assessed. Methods and results A total of 313 patients (197 males) with a mean age of 44.8 ± 16.5 years were included, with symptoms including aborted SCD (7%), ventricular arrhythmias (47%), additional chest pain (42%), syncopes (17%), and atrial arrhythmias (12%); follow-up duration was 8.5 years. The total annual mortality rate was 0.3%, from SCD in 0.2% and heart failure in 0.1%. In symptomatic or high-risk patients, the annual rate of malignant ventricular arrhythmias was 6 and 9%, respectively. In multivariate analysis, a risk factor for SCD was left ventricular dysfunction. The annual heart failure rate was low at 0.5%; four patients died, two had heart transplants and one tricuspid reconstruction. Intrathoracic cardioverter-defibrillator (ICD) therapy was initiated in 35 patients. Adequate shocks after 6–72 months were delivered in 77%; in the majority aborted sudden death with documented ventricular fibrillation and unstable ventricular tachycardia were underlying arrhythmias. Conclusions The clinical course of ARVD/C is characterized by a high rate of recurrent malignant ventricular arrhythmias in initially symptomatic and high-risk cases, and is uneventful in primarily asymptomatic affected individuals. The spectrum of clinical symptoms represents a warning symptom initiating the so-called ‘hot phase’ of the disease in many cases. ICD treatment is highly effective in cases of aborted SCD and unstable ventricular tachycardia.
Interobserver agreement of confocal laser endomicroscopy for bladder cancer.

BACKGROUND AND PURPOSE Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer. METHODS Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor. Interobserver agreement was determined using the κ statistic. RESULTS Of the 31 bladder regions analyzed, 19 were cancer and 12 were benign. For cancer diagnosis, experienced CLE urologists had substantial agreement for both CLE and WLC+CLE (90%, κ 0.80) compared with moderate agreement for WLC alone (74%, κ 0.46), while novice CLE urologists had moderate agreement for CLE (77%, κ 0.55), WLC (78%, κ 0.54), and WLC+CLE (80%, κ 0.59). Pathologists had substantial agreement for CLE (81%, κ 0.61), and nonclinical researchers had moderate agreement (77%, κ 0.49) in cancer diagnosis. For cancer grading, experienced CLE urologists had fair to moderate agreement for CLE (68%, κ 0.64), WLC (74%, κ 0.67), and WLC+CLE (53%, κ 0.33), as did novice CLE urologists for CLE (53%, κ 0.39), WLC (66%, κ 0.50), and WLC+CLE (61%, κ 0.49). Pathologists (65%, κ 0.55) and nonclinical researchers (61%, κ 0.56) both had moderate agreement for CLE in cancer grading. CONCLUSIONS CLE is an adoptable technology for cancer diagnosis in novice CLE observers after a short training with moderate interobserver agreement and diagnostic accuracy similar to WLC alone. Experienced CLE observers may be capable of achieving substantial levels of agreement for cancer diagnosis that is higher than with WLC alone.