Miracle-dz/UniFAR-FTUs huggingface dataset:
Ten-Year Clinical Outcomes From a Trial of Three Limus-Eluting Stents With Different Polymer Coatings in Patients With Coronary Artery Disease: Results From the ISAR-TEST 4 Randomized Trial

Background: New-generation drug-eluting stents offer the potential for enhanced late outcomes in comparison with early generation drug-eluting stents. However, assessment of extended long-term outcomes for these devices is lacking, especially regarding the comparison between new-generation drug-eluting stents with biodegradable or permanent polymers. The aim of this study is to compare the efficacy and safety of biodegradable polymer-based sirolimus-eluting stents (BP-SES; Yukon Choice PC) versus permanent polymer-based everolimus-eluting stents (PP-EES; Xience) versus early generation permanent polymer-based sirolimus-eluting stents (PP-SES; Cypher) at 10-year follow-up. Methods: Overall, 2603 patients were randomized to treatment with BP-SES (n=1299), PP-EES (n=652), or PP-SES (n=652). The primary end point of this analysis was major adverse cardiac event, the composite of death, myocardial infarction, or target lesion revascularization. The main secondary end point of interest was definite/probable stent thrombosis. Follow-up at 10 years was available in 83% of the study patients. Results: The 10-year incidence of major adverse cardiac event (BP-SES 47.7% versus PP-EES 46.0% versus PP-SES 54.9%, P=0.003) and mortality (BP-SES 31.8% versus PP-EES 30.3% versus PP-SES 37.2%, P=0.02) was different among the groups. Definite/probable stent thrombosis was not significantly different among the groups (BP-SES 1.8% versus PP-EES 2.5% versus PP-SES 3.7%, P=0.09). Definite stent thrombosis was significantly different among the groups (BP-SES 1.1% versus PP-EES 0.8% versus PP-SES 2.4%, P=0.03). There were no significant differences between BP-SES and PP-EES. Conclusions: In this unique long-term outcome analysis, BP-SES and PP-EES showed comparable clinical outcomes out to 10 years. PP-SES had higher rates of major adverse cardiac events and definite stent thrombosis. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT00598676.
Deciphering the Molecular Profile of Lung Cancer: New Strategies for the Early Detection and Prognostic Stratification

Recent advances in radiological imaging and genomic analysis are profoundly changing the way to manage lung cancer patients. Screening programs which couple lung cancer risk prediction models and low-dose computed tomography (LDCT) recently showed their effectiveness in the early diagnosis of lung tumors. In addition, the emerging field of radiomics is revolutionizing the approach to handle medical images, i.e., from a “simple” visual inspection to a high-throughput analysis of hundreds of quantitative features of images which can predict prognosis and therapy response. Yet, with the advent of next-generation sequencing (NGS) and the establishment of large genomic consortia, the whole mutational and transcriptomic profile of lung cancer has been unveiled and made publicly available via web services interfaces. This has tremendously accelerated the discovery of actionable mutations, as well as the identification of cancer biomarkers, which are pivotal for development of personalized targeted therapies. In this review, we will describe recent advances in cancer biomarkers discovery for early diagnosis, prognosis, and prediction of chemotherapy response.
The Association of Lifetime Nonmedical Use of Prescription Pain Killers and Heroine Use

OF THE THESIS The Association of Lifetime Nonmedical Use of Prescription Painkillers and Heroin Use by Charles J. Robertson Master of Public Health with a Concentration in Epidemiology San Diego State University, 2015 Background Heroin and prescription painkiller use are both major public health concerns within the United States. Although the rate of prescription painkiller overdose is decreasing, the rate of heroin-related overdose is increasing. There are concerns that this increase is due to individuals progressing from nonmedical pain reliever (NMPR) use to heroin. Methods Data were obtained through a nationwide survey on drug use. The sample was representative of the United States in regard to age, gender, and race/ethnicity. Correlations between heroin and NMPR were found using both bivariate analysis and multivariable analysis after adjusting for previous drug use and demographic characteristics. Results Of the 55,160 subjects included in the analysis, 840(1.5%) reported having used heroin at least once in their life. Out of the entire sample, 4664(8.5%) reported previous NMPR use. The odds of heroin use were 3.5 times higher for those who had used NMPR than those who had not used NMPR (95% CI=2.9-4.4). Discussion These results indicate that the current increase of heroin may be due, at least in part, to individuals progressing from NMPR to heroin.
The time courses of runners’ recovery-stress responses after a mountain ultra-marathon: Do appraisals matter?

Abstract Objectives: The aim of this study was to: (a) examine the time courses of runners’ recovery-stress states within the month following a demanding Mountain Ultra-Marathon (MUM) race; and (b) explore the role of primary and secondary appraisals in these trajectories. Design: A seven-wave one-month longitudinal design was used with one measurement point within two days before the race to measure appraisals and six time points within the month following the race to assess recovery-stress states experienced by athletes. Method: A multilevel growth curve analysis approach was used among a sample of 29 MUM runners. Results: Recovery-stress states were characterized by distinct trajectories during the month following MUM race. Results of multilevel growth curve analyses showed significant linear increases of general and total recovery, significant linear decreases of general, sport-specific and total stress and a positive quadratic effect of squared time (U shape over time) on specific recovery. Primary appraisal significantly positively predicted levels of sport-specific recovery, total, general and sport-specific stress and significantly negatively predicted total and general recovery. Secondary appraisal significantly negatively predicted total and general stress. Conclusions: This study provided insights into the role played by appraisals on the recovery-stress states experienced by MUM runners the month following a demanding MUM race. Operational strategies were suggested in order to optimize the recovery-stress balance and in turn psychological adaptation processes in response to an ultra-endurance race.
Effect of subgroup-specific multimodal therapy on chronic spinal back pain and function—a prospective inpatient multicentre clinical trial in Germany

Abstract Treatment modalities of spinal pain patients are discussed diversely, and different multimodal therapy programs have been developed. Purpose of the present study was to evaluate therapy outcome and effectiveness of an inpatient interdisciplinary and multimodal treatment program. This prospective multicentre clinical trial has been performed with patients from orthopedic hospitals receiving a functional musculoskeletal therapy pathway. Outcome measures were pain intensity and back-specific function (Oswestry Disability Index) before (T1) and after the intervention (T2) as well as after 6 and 12 months (T3, T4). Statistical approach included parametric (t test) and nonparametric (Wilcoxon-test) tests and the calculation of effect sizes. Additionally, a statistical subgroup analysis based on selected parameters (degree of pain chronicity, gender, and age) was performed using linear mixed models. In total, 249 patients (42.6% men, 57.4% women) with spinal pain were included, 133 patients were accessible for follow-up at T3 and 106 patients at T4. Average pain (AP) reduced significantly (P <.001) from T1 to T4 with an effect size of 0.99. Back-specific function also improved (P <.001) over all measuring time points (TP) (effect size: 0.63). Furthermore, the statistical subgroup analysis demonstrated the efficacy of the treatment concept within the subgroup parameters chronicity degree and age. A functional musculoskeletal therapy pathway including treatment of musculoskeletal dysfunctions appears to be beneficial in terms of treating pain and function. Pain chronicity and age seems to be factors influencing therapy outcome. Further studies are needed to examine the superiority of these inpatient programs for back pain including control groups.
Brain-Derived Neurotrophic Factor Is Required for the Neuroprotective Effect of Mifepristone on Immature Purkinje Cells in Cerebellar Slice Culture

Endogenous γ-aminobutyric acid (GABA)-dependent activity induces death of developing Purkinje neurons in mouse organotypic cerebellar cultures and the synthetic steroid mifepristone blocks this effect. Here, using brain-derived neurotrophic factor (BDNF) heterozygous mice, we show that BDNF plays no role in immature Purkinje cell death. However, interestingly, BDNF haploinsufficiency impairs neuronal survival induced by mifepristone and GABAA-receptors antagonist (bicuculline) treatments, indicating that the underlying neuroprotective mechanism requires the neurotrophin full expression.
Triaging Patient Referrals to a Non‐Tertiary Public Hospital General Paediatric Clinic: Who are we Declining and why?

toad poisoning and can be improved within 1–4 h of administration of digoxin Fab. However, supply of this medication is limited, even in tertiary hospitals and especially outside of routine working hours. Sinus bradycardia, conduction disturbances, firstdegree atrioventricular block and sinoatrial arrest are the most common arrhythmias seen in children with cardiac glycoside toxicity. Further doses of digoxin Fab may be necessary to achieve complete resolution of toxicity; however, the use of digoxin Fab can precipitate hypokalaemia, necessitating close electrolyte monitoring. Admission to an intensive care unit, continuous cardiac monitoring, serial electrolyte monitoring and consultation with a clinical toxicologist should be considered if signs of toxicity are present following cane toad ingestion.
Breathing-motion induced interplay effects for stereotactic body radiotherapy of liver tumours using flattening-filter free volumetric modulated arc therapy

The purpose of this study was to investigate breathing-motion induced interplay effects for stereotactic body radiotherapy (SBRT) of liver tumours treated with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT). Ten patients previously treated with liver SBRT were included in this study. All patients had four-dimensional computed tomography (4DCT) scans acquired prior to treatment. The 4DCT was sorted into 8–10 phases covering an equal time interval. A FFF VMAT plan was created for one fraction in the mid-ventilation phase for each patient. To generate dose distributions including both interplay effects and dose blurring, a sub-plan was calculated for each phase. The total dose distributions were accumulated to the mid-ventilation phase using the deformed vector fields (DVF) from deformable image registration between the corresponding CT and the mid-ventilation phase CT. A blurred dose distribution, not including interplay effects, was also obtained by distributing the delivery of the whole plan uniformly on all phases, and was similarly accumulated to the mid-ventilation phase. To isolate interplay effects, this blurred dose distribution was subtracted from the total dose distribution with interplay effects. The near minimum dose (D98%), mean dose (Dmean), heterogeneity index (HI), and the near minimum dose difference (ΔD98%) between the accumulated dose distributions with and without interplay effects were calculated within the gross tumour volume (GTV) for each patient. Comparing the accumulated dose distributions with and without interplay effects, the D98% decreased for nine of the ten patients and the HI increased for all patients. The median and minimum differences in D98% were −2.1% and −5.0% (p = 0.006), respectively, and the median HI significantly increased from 6.2% to 12.2% (p = 0.002). The median ΔD98% was −4.0% (range −7% to −1.5%). In conclusion, statistically significant breathing-induced interplay effects were observed for a single fraction of FFF VMAT liver SBRT, resulting in heterogeneous dose distributions within the GTV.
MicroRNAs in Autoimmune Sjögren’s Syndrome

MicroRNAs (miRNAs), small non-coding RNAs, have been implicated in various diseases and cellular functions as microregulators of gene expression. Although the history of miRNA investigation in autoimmune Sjögren’s syndrome (SjS) is fairly short, a substantial amount of data has already been accumulated. These findings clearly indicate potential clinical implications of miRNAs, such as autoantigen expression and autoantibody production, viral miRNAs regulating the calcium signaling pathway, and aberrant immune cell regulation and cytokine production. Research endeavors in the field are currently underway to select disease-specific diagnostic and prognostic biomarkers by utilizing different types of tissues or biological specimens of SjS patients. Various techniques for miRNA analysis with different stringencies have been applied, with the most recent one being next-generation sequencing. This review compiles and highlights differentially-expressed miRNAs in various samples collected from SjS patients and their potential implications in the pathogenesis of SjS. To facilitate the development of miRNA-targeted personalized therapy in the future, we urge more follow-up studies that confirm these findings and elucidate the immunopathological roles of differentially-expressed miRNAs. Furthermore, improved diagnostic criteria for the disease itself will minimize sampling errors in patient recruitment, preventing the generation of inconsistent data.
Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications

The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(l-lysine-co-d-phenylalanine) (P(Lys-co-dPhe)) and poly(l-glutamic acid-co-d-phenylalanine) (P(Glu-co-dPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied. Additionally, the investigation of their biodegradability and cytotoxicity was performed. The prolonged stability of nanospheres was achieved via introduction of d-amino acids into the polypeptide structure. The cytotoxicity of nanospheres obtained was tested using HEK-293 cells. It was proved that no cytotoxicity up to the concentration of 500 µg/mL was observed. C-peptide delivery systems were realized in two ways: (1) peptide immobilization on the surface of P(Glu-co-dPhe) nanospheres; and (2) peptide encapsulation into P(Lys-co-dPhe) systems. The immobilization capacity and the dependence of C-peptide encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The kinetic of drug release was studied at model physiological conditions. Novel formulations of a long-acting C-peptide exhibited their effect ex vivo by increasing activity of erythrocyte Na+/K+-adenosine triphosphatase.
Extreme learning machine Cox model for high‐dimensional survival analysis

Some interesting recent studies have shown that neural network models are useful alternatives in modeling survival data when the assumptions of a classical parametric or semiparametric survival model such as the Cox (1972) model are seriously violated. However, to the best of our knowledge, the plausibility of adapting the emerging extreme learning machine (ELM) algorithm for single‐hidden‐layer feedforward neural networks to survival analysis has not been explored. In this paper, we present a kernel ELM Cox model regularized by an L0‐based broken adaptive ridge (BAR) penalization method. Then, we demonstrate that the resulting method, referred to as ELMCoxBAR, can outperform some other state‐of‐art survival prediction methods such as L1‐ or L2‐regularized Cox regression, random survival forest with various splitting rules, and boosted Cox model, in terms of its predictive performance using both simulated and real world datasets. In addition to its good predictive performance, we illustrate that the proposed method has a key computational advantage over the above competing methods in terms of computation time efficiency using an a real‐world ultra–high‐dimensional survival data.
Women Remain at Risk of Iodine Deficiency during Pregnancy: The Importance of Iodine Supplementation before Conception and Throughout Gestation

In Australia, pregnant women are advised to take an iodine supplement (I-supp) (150 µg/day) to reduce risks to the foetus associated with iodine deficiency (ID). To examine the impact of this recommendation on iodine status, and to identify factors that contribute to adequacy during gestation, supplement use and Urinary Iodine Concentration (UIC) was measured in 255 pregnant women (gestation range 6 to 41 weeks) in Tasmania. The median UIC (MUIC) of 133 µg/L (Inter-quartile range 82–233) was indicative of ID, being below the 150–249 µg/L range for adequacy during pregnancy. Women taking an iodine-containing-supplement (I-supp) had a significantly higher MUIC (155 µg/L) (n = 171) compared to the combined MUIC (112.5 µg/L) (n = 84) of those who had never (120 µg/L) (n = 61) or were no longer taking an I-supp (90 µg/L) (n = 23) (p = 0.017). Among women reporting I-supp use, the MUIC of those commencing the recommended 150 µg/day prior to conception was significantly higher than those starting supplementation following pregnancy confirmation: 196 (98–315) µg/L (n = 45) versus 137.5 (82.5–233.5) µg/L (n = 124), p = 0.032. Despite recommendations for iodine supplementation pregnant Tasmanian women remain at risk of ID. Commencing an I-supp of 150 µg/day prior to conception and continuing throughout pregnancy is required to ensure adequacy. Timely advice regarding the importance of adequate iodine nutrition, including supplementation is needed to reduce the risk of irreversible in utero neurocognitive damage to the foetus.
Loss of fibrinogen in zebrafish results in an asymptomatic embryonic hemostatic defect and synthetic lethality with thrombocytopenia

Essentials Loss of fibrinogen in zebrafish has been previously shown to result in adult onset hemorrhage Hemostatic defects were discovered in early fga−/− embryos but well tolerated until adulthood Afibrinogenemia and thrombocytopenia results in synthetic lethality in zebrafish. Testing human FGA variants of uncertain significance in zebrafish identified causative mutations
Prevalence and correlations of temporomandibular disorders in Northern Jordan using diagnostic criteria axis I.

AIM The aim of the present study was to document the prevalence and possible correlations of temporomandibular disorders (TMD) in a sample of participants from Northern Jordan. METHODS A total of 368 adult participants were consecutively selected from visitors to a major health facility in Northern Jordan and examined according to the diagnostic criteria (DC) for TMD (DC/TMD) protocol. Patients with conditions that could interfere with TMD diagnosis were excluded. Pearson correlation and analysis of variance statistical tests were applied. Statistical significance was set at P ≤ 0.05, with a 95% confidence interval. RESULTS A total of 98 patients (26.7%) had 1 TMD diagnoses; 60 participants (16.3%) had a pain-related TMD diagnosis, 48 (13%) had intra-articular joint disorders (IAD), and 16 had both pain-related TMD and IAD. In addition, six (1.6%) participants were found to have degenerative joint disease. Females were found to have a higher prevalence of pain-related TMD diagnoses (r = 0.111, P = 0.034) and headache (r = 0.129, P = 0.013) than males. Clicking was positively related to both pain-related TMD (r = 0.154, P = 0.003) and IAD (r = 0.576, P = 0.000). CONCLUSION The frequency of TMD and related features was reported in a Northern Jordanian population using DC/TMD for the first time, and the results are comparable to other populations in similar study settings.
Determination of the prevalence of viral aetiology of diarrhea in children less than 5 years of age in Baghdad province

Determination the prevalence of viral, parasitic and bacterial etiology of gastroenteritis in children less than 5 years of age with diarrhea in various hospitals of Baghdad province. A total of 250 stool samples were collected from various hospitals of Baghdad province . Samples were investigated for bacterial and parasitic enteropathogens using microscopic examination. Bacterial culture of stool samples was done in different culture media including MacConkey, XLD, DCA, TCBS and campylobacter media, TCBS and selenite F broth and bacterial growth was examined by analytical profile index (Api20E) system , commercial antisera and colonies characteristics. Enzyme immunoassays were used to identify Group A rotavirus ,Astrovirus and enteric adenovirus Out of 250, 106 children (42.4%) were diagnosed as viral infection of which Rotavirus was found in the majority of cases 91 (36.4%), Adenovirus was detected in 15(6%) patients. bacterial causes were 63 (25.2%) of which 36 (14.4%) were Escherichia coli (ETEC), 12 (4.8%) were Shigella flexneri , 6(2.4%) were Campylobacter jejunii and 9(3.6) were Salmonella enteritidis . Entamoeba histolytica 22 (8.8%) and Giardia lamblia 22 (8.8%) were the most frequent parasite which isolated from all diarrheal stool specimens. Also from total of 250 samples, 40 samples (16%) were dysenteric stool specimens (bloody diarrhea) and the most common pathogens isolated from dysenteric stool specimens were E.histolytica 22(8.8%), Shigella flexneri 12(4.8%) and Campylobacter jejunii 6 (2.4%). The current study revealed a high prevalence of rotavirus as most common cause of diarrhoea in children less than 5 years of age.
Intramuscular Nerve Distribution in the Medial Rectus Muscle and Its Clinical Implications

ABSTRACT Purpose: The intramuscular nerve distribution in the extraocular muscles may be crucial for understanding their physiological and pathological responses. This study aimed to determine the oculomotor nerve distribution in the medial rectus muscle (MR) using Sihler’s staining. Method: Thirty-seven MRs from 23 cadavers were investigated. The MR including the oculomotor nerve was finely dissected from its origin to its insertion point into the sclera. The total length of the muscle-belly, tendon length and maximum width of the muscle were measured. We evaluated the pattern of distribution and the length of the intramuscular nerve distribution by gross observation after performing Sihler’s staining, which is a method for visualizing the distribution of nerve fibers without alteration of the nerve. Results: The total length of the muscle-belly, tendon length, and muscle width were 37.6 ± 4.6 mm, 4.4 ± 1.9 mm, and 10 ± 1.8 mm, respectively. The oculomotor nerve enters the MR at a mean of two-fifths along the muscle (24 ± 2.0 mm posterior to the insertion point) and then typically divides into a few branches (mean of 2.1). The intramuscular nerve distribution showed a Y-shaped ramification, forming the terminal nerve plexus, and its course typically finished at around 17 ± 1.5 mm posterior to the muscle insertion point by gross observation. The nerve plexus in the upper part generally coursed more distally than the lower part. Conclusion: This new information regarding the nerve distribution pattern of MR will be helpful for understanding MR function and the diverse pathophysiology of strabismus.