Miracle-dz/UniFAR-FTUs huggingface dataset:
Escitalopram in major depressive disorder: a multicenter, randomized, double‐blind, fixed‐dose, parallel trial in a Chinese population

Escitalopram, the S‐enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM‐IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double‐blind, fixed‐dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17‐item Hamilton Depression Rating Scale (HAM‐D‐17) and the Montgomery–Åsberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM‐D‐17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM‐D‐17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM‐D‐17: “depressed mood” (P =.023) and “work and interest” (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as “depressed mood” and “work and interest. ” Depression and Anxiety 0:1–9, 2006. © 2006 Wiley‐Liss, Inc.
Sequencing biological acidification of waste-activated sludge aiming to optimize phosphorus dissolution and recovery

ABSTRACT Phosphorus (P) recovery in wastewater treatment plants (WWTP) as pure crystals such as struvite (MgNH4PO4.6H2O), potassium struvite (KMgPO4.6H2O) and calcium phosphates (e.g. Ca3(PO4)2) is an already feasible technique that permits the production of green and marketable fertilizers and the reduction of operational costs. Commercial crystallizers can recovery more than 90% of soluble P. However, most of the P in WWTP sludge is unavailable for the processes (not dissolved). P solubilization and separation are thus the limiting steps in P-crystallization. With an innovative two-step sequencing acidification strategy, the current study has aimed to improve biological P solubilization on waste-activated sludge (WAS) from a full-scale plant. In the first step (P-release), low charges of organic waste were used as co-substrates of WAS pre-fermentation, seeking to produce volatile fatty acids to feed the P-release by Polyphosphate-accumulating organisms, while keeping its optimal metabolic pH (6–7). In this phase, milk serum, WWTP grease, urban organic waste and collective restaurant waste were individually applied as co-substrates. In the second step (P-dissolution), pH 4 was aimed at as it allows the dissolution of the most common precipitated species of P. Biological acidification was performed by white sugar addition, as a carbohydrate-rich organic waste model, which was compared to chemical acidification by HCl (12M) addition. With short retention times (48–96 h) and without inoculum application, all experiences succeeded on P solubilization (37–55% of soluble P), principally when carbohydrate-rich co-substrates were applied. Concentrations from 270 to 450 mg were achieved.
Leucinostatin A inhibits prostate cancer growth through reduction of insulin‐like growth factor‐I expression in prostate stromal cells

Targeting stroma in tumor tissues is an attractive new strategy for cancer treatment. We developed in vitro coculture system, in which the growth of human prostate cancer DU‐145 cells is stimulated by prostate stromal cells (PrSC) through insulin‐like growth factor I (IGF‐I). Using this system, we have been searching for small molecules that inhibit tumor growth through modulation of tumor‐stromal cell interactions. As a result, we have found that leucinostatins and atpenins, natural antifungal antibiotics, inhibit the growth of DU‐145 cells cocultured with PrSC more strongly than that of DU‐145 cells alone. In this study we examined the antitumor effects of these small molecules in vitro and in vivo. When DU‐145 cells were coinoculated with PrSC subcutaneously in nude mice, leucinostatin A was found to significantly suppress the tumor growth more than atpenin B. The antitumor effect of leucinostatin A in vivo was not obtained against the tumors of DU‐145 cells alone. RT‐PCR experiments revealed that leucinostatin A specifically inhibited IGF‐I expression in PrSC without effect on expressions of other IGF axis molecules. Leucinostatins and atpenins are known to abrogate mitochondrial functions. However, when we used mitochondrial DNA‐depleted, pseudo‐ρ0 cells, we found that one of leucinostain A actions certainly depended on mitochondrial function, but it actually inhibited the growth of DU‐145 cells more strongly in coculture with pseudo‐ρ0 PrSC and reduced IGF‐I expression in pseudo‐ρ0 PrSC. Taken together, our results suggested that leucinostatin A inhibited prostate cancer cell growth through reduction of IGF‐I expression in PrSC.
Lipopolysaccharide differentially regulates microglial trk receptor and neurotrophin expression

Activated brain microglia play a pivotal role in inflammatory and degenerative disorders, mediating immune function and producing toxic and trophic agents. We previously reported that microglia express neurotrophins and that neurotrophin‐3 (NT‐3) increases microglial proliferation and phagocytosis, processes associated with cellular activation. However, mechanisms regulating responsiveness to NT‐3 and expression of NT‐3 in activated microglia remain undefined. To investigate mechanisms governing microglial responsiveness to neurotrophins, we determined whether microglia express trk C, the high‐affinity receptor for NT‐3, and whether the inflammatory agent lipopolysaccharide (LPS) regulates receptor expression. Trk C mRNA was expressed by unstimulated microglia, and both trk C mRNA and protein were dramatically increased by LPS. In contrast, expression of trk A, the high‐affinity receptor for nerve growth factor (NGF), was down‐regulated by LPS. Consequently, the same stimulus differentially influences responsiveness of microglia to distinct trophins. In addition, LPS induced microglial NT‐3 expression, suggesting that increases in both the ligand and receptor modulate NT‐3 effects on microglia. Regulation was specific, since brain‐derived neurotrophic factor (BDNF) and NT‐4/5 expression were unaltered by LPS. In sum, our findings raise the possibility that microglial NT‐3 regulates their response to inflammation through autocrine mechanisms: LPS modulates both trk C and NT‐3 which, in turn, regulate microglial function. J. Neurosci. Res. 54:117–122, 1998. © 1998 Wiley‐Liss, Inc.
Efficacy of Tocilizumab in Conventional Treatment–Refractory Adult‐Onset Still's Disease: Multicenter Retrospective Open‐Label Study of Thirty‐Four Patients

Adult‐onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment.
Toxicity and Biomedical Imaging of Layered Nanohybrids in the Mouse

Layered nanohybrids (LNH) are a promising nonviral system allowing controlled drug and DNA delivery. In order to test the toxicity of LNH consisting of a magnesium/aluminum core, mice were subjected to subcutaneous, intraperitoneal, and intravenous injections of these nanoparticles at three doses. Intravenous injections resulted in 8% (1 out of 12) lethality at doses 100 μl and 200 μl of 6.96 × 10−4 M solution, while all mice survived after LNH administration by any other routes. Histopathological alterations were limited to mild localized inflammatory lesions in the lungs and the dermis after intravenous and subcutaneous administration, respectively. LNH labeled with Lucifer Yellow were readily detectable in both locations by fluorescent microscopy. To test their potential for intravital imaging, LNH-Lucifer Yellow were injected into the ovarian bursa and successfully visualized by multiphoton microscopy within the ovarian surface epithelial cells. In similar experiments, the ovary and the ovarian bursa were readily detectable by magnetic resonance imaging after administration of modified LNH, where aluminum was substituted for gadolinium. Taken together, these results demonstrate minimal in vivo toxicity of LNH and illuminate their potential as multifunctional nanoscale particles suitable for combination of intravital biomedical imaging with controlled drug release.
Liver tumor laser ablation – increase in the subacute ablation lesion volume detected with post procedural MRI

Background: The use of image-guided thermoablative methods in liver tumor treatment has expanded rapidly due to encouraging results and advanced imaging. However, little is known about the treatment-induced tissue response and effects on imaging findings during the subacute post procedural period. Purpose: To study the development of subacute ablation zone volume with magnetic resonance imaging (MRI) after laser-mediated liver tumor thermal therapy. Material and Methods: In all, 16 laser ablations were performed on 16 liver tumors resulting in 16 ablation zones in 11 consecutive patients. A low-field 0.23 T C-arm MRI scanner was used for imaging and procedural guidance. Repeated dynamic contrast-enhanced T1, contrast-enhanced T1 FSE, and T2 FSE studies of liver were performed at 0 and 72 h after the procedure. Ablation zone volumes were registered from the acquired image data. Results: MRI scans showed a significant increase of ablation volume in all imaging sequences obtained at 72 h after the initial therapy. Conclusion: After laser ablation, there is a progressive perfusion decrease in the ablation site leading to an increase in the ablation volume. Post procedural baseline MRI at 72 h from the treatment provides more precise information about the ablation result than can be obtained with immediate post procedural MRI.
Prothrombin complex concentrates in emergency bleeding disorders

The use of prothrombin complex concentrates (PCCs), a heterogeneous combination of coagulation factors and counterbalancing inhibitor components, has broadened in recent years beyond single‐factor replacement in conditions such as hemophilia B, to encompass emergency reversal of anticoagulation secondary to oral vitamin K antagonists, ie, warfarin therapy. PCCs also have been studied in other bleeding disorders, such as surgery‐related and trauma‐related bleeding. This review provides an updated examination of the differences among PCC formulations, their potential role in the management of bleeding disorders, and the primary safety issues affecting their use. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Percutaneous endovascular repair of infrarenal abdominal aortic aneurysms: a feasibility study.

BACKGROUND Endovascular grafting has markedly reduced the invasiveness of the treatment of abdominal aortic aneurysms. By using a modification of technique for available closure devices, we have been able to achieve percutaneous repair of aneurysms. This study reviewed our initial experience with this technique. METHODS Demographics and background data from patients undergoing endovascular repair of abdominal aortic aneurysms were reviewed from prospectively collected registry data. Operative notes and angiographic and computed tomography scan data were retrospectively reviewed to assess the success of the percutaneous approach. RESULTS Fourteen patients have undergone percutaneous placement of the AneuRx (Medtronic, Sunnyvale, Calif) endovascular graft, with a modification of the technique for the Prostar (Perclose, Redwood City, Calif) device for access site closure. Main graft body introduction with a 22F sheath proved successful in nine of 12 (75%) deployments. Contralateral limb deployment through a 16F sheath was successful in 10 of 14 deployments (71.4%). Reasons for conversion to open groin incisions include inadequate percutaneous hemostasis (six cases), iliofemoral dissection (four cases), device failure (one case), and compromised distal flow (one case). Percutaneous deployment success appears to be improved with larger iliac artery dimensions, decreased calcification, and limited tortuosity, because of the limitation of complications related to delivering a larger diameter sheath. Of the 13 percutaneous endograft insertions that were attempted, six (46.2%) were completely successful. CONCLUSION Percutaneous deployment of available devices is technically feasible by using modifications of technique with percutaneous closure devices, despite large introducer sizes. Further experience with this technique offers the potential for identifying patients in whom this will prove successful and for even further reducing hospital stay and recovery times for aneurysm repair.
Teaching and learning queueing theory concepts using Tangible User Interfaces

Tangible User Interfaces (TUI) have emerged in the past years as effective computing platforms that intertwine digital information and visualization with physical interactivity. Whilst successfully capitalizing on these properties within primary education to engage and educate children in an entertaining manner, TUI systems have seen limited deployment in more complex scenarios. To this end, this paper investigates the aptness and effectiveness of implementing TUI systems to enhance teaching and learning within higher educational institutes in order to aid the understanding of complex and abstract concepts. The proposal augments mere simulation processes by developing a table-top architecture to allow the real-time interaction and visualization of queuing theory concepts. The paper describes the deployment of the TUI framework within an undergraduate computer networks degree whereby the quantitative effectiveness of this system is assessed from a teaching and learning perspective within an engineering pedagogy.
Metabolism of the Endocannabinoid Anandamide: Open Questions after 25 Years

Cannabis extracts have been used for centuries, but its main active principle ∆9-tetrahydrocannabinol (THC) was identified about 50 years ago. Yet, it is only 25 years ago that the first endogenous ligand of the same receptors engaged by the cannabis agents was discovered. This “endocannabinoid (eCB)” was identified as N-arachidonoylethanolamine (or anandamide (AEA)), and was shown to have several receptors, metabolic enzymes and transporters that altogether drive its biological activity. Here I report on the latest advances about AEA metabolism, with the aim of focusing open questions still awaiting an answer for a deeper understanding of AEA activity, and for translating AEA-based drugs into novel therapeutics for human diseases.
Bacillus anthracis Toxins Inhibit Human Neutrophil NADPH Oxidase Activity1

Bacillus anthracis, the causative agent of anthrax, is a Gram-positive, spore-forming bacterium. B. anthracis virulence is ascribed mainly to a secreted tripartite AB-type toxin composed of three proteins designated protective Ag (PA), lethal factor, and edema factor. PA assembles with the enzymatic portions of the toxin, the metalloprotease lethal factor, and/or the adenylate cyclase edema factor, to generate lethal toxin (LTx) and edema toxin (ETx), respectively. These toxins enter cells through the interaction of PA with specific cell surface receptors. The anthrax toxins act to suppress innate immune responses and, given the importance of human neutrophils in innate immunity, they are likely relevant targets of the anthrax toxin. We have investigated in detail the effects of B. anthracis toxin on superoxide production by primary human neutrophils. Both LTx and ETx exhibit distinct inhibitory effects on fMLP (and C5a) receptor-mediated superoxide production, but have no effect on PMA nonreceptor-dependent superoxide production. These inhibitory effects cannot be accounted for by induction of neutrophil death, or by changes in stimulatory receptor levels. Analysis of NADPH oxidase regulation using whole cell and cell-free systems suggests that the toxins do not exert direct effects on NADPH oxidase components, but rather act via their respective effects, inhibition of MAPK signaling (LTx), and elevation of intracellular cAMP (ETx), to inhibit upstream signaling components mediating NADPH oxidase assembly and/or activation. Our results demonstrate that anthrax toxins effectively suppress human neutrophil-mediated innate immunity by inhibiting their ability to generate superoxide for bacterial killing.
Demographic Ageing and its Economic Consequences in Croatia

The paper describes the most pronounced features of demographic changes in the recent history of the Republic of Croatia, emphasizing main drivers of decline of the Croatian population. In the elaboration of recent demographic trends the country specific phenomena affecting demographic developments are discerned from the more universal phenomena. After that, the paper presents basic variants of the demographic projections for the period up to 2050, pointing at those elements of the demographic projections that could have important implications on future economic developments such as fiscal sustainability, labour market trends, and consequently, on economic growth. After that, the paper tries to identify possibilities of mitigating potentially detrimental impact of demographic changes on the economy, by implementing reforms in the most vulnerable areas – labour market, health system and pension system. The paper concludes with the finding that negative effects of demographic ageing could be mitigated if the government recognizes long-term demographic developments and reacts timely by implementing carefully designed policy measures and by supporting adequate information campaigns.
Lower hospital mortality and complications after pediatric hematopoietic stem cell transplantation*

Objective:To assess protective and risk factors for mortality among pediatric patients during initial care after hematopoietic stem cell transplantation (HSCT) and to evaluate changes in hospital mortality. Design:Retrospective cohort using the 1997, 2000, and 2003 Kids Inpatient Database, a probabilistic sample of children hospitalized in the United States with a procedure code for HSCT. Setting:Hospitalized patients in the United States submitted to the database. Patients:Age, <19 yrs. Interventions:None. Measurements and Main Results:Hospital mortality significantly decreased from 12% in 1997 to 6% in 2003. Source of stem cells changed with increased use of cord blood. Rates of sepsis, graft versus host disease, and mechanical ventilation significantly decreased. Compared with autologous HSCT, patients who received an allogenic HSCT without T-cell depletion were more likely to die (adjusted odds ratio, 2.4; 95% confidence interval, 1.5, 3.9), while children who received cord blood HSCT were at the greatest risk of hospital death (adjusted odds ratio, 4.8; 95% confidence interval, 2.6, 9.1). Mechanical ventilation (adjusted odds ratio, 26.32; 95% confidence interval, 16.3–42.2), dialysis (adjusted odds ratio, 12.9; 95% confidence interval, 4.7–35.4), and sepsis (adjusted odds ratio, 3.9; 95% confidence interval, 2.5–6.1) were all independently associated with death, while care in 2003 was associated with decreased risk (adjusted odds ratio, 0.4; 95% confidence interval, 0.2–0.7) of death. Conclusions:Hospital mortality after HSCT in children decreased over time as did complications including need for mechanical ventilation, graft versus host disease, and sepsis. Prevention of complications is essential as the need for invasive support continues to be associated with high mortality risk.
Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing–remitting MS

Objective: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg daily vs the approved 20-mg formulation in relapsing–remitting multiple sclerosis. Methods: Eligibility criteria included clinically definite multiple sclerosis, Expanded Disability Status Scale score 0 to 5.0, no previous use of GA, at least one relapse in the previous year, and 1 to 15 gadolinium-enhancing (GdE) lesions on a screening MRI. MRI was repeated at months 3, 7, 8, and 9, and neurologic examinations were performed at baseline and months 3, 6, and 9. Results: Of 229 subjects screened, 90 were randomly assigned to GA 20 mg (n = 44) or 40 mg (n = 46). The groups were well matched at baseline for demographic, clinical, and MRI characteristics. The primary efficacy endpoint, total number of GdE lesions at months 7, 8, and 9, showed a trend favoring the 40-mg group (38% relative reduction, p = 0.0898). A difference between the two dose groups emerged as early as month 3 (52% reduction; p = 0.0051). There was a trend favoring the 40-mg group for relapse rate with benefit on proportion of relapse-free subjects (p = 0.0183) and time to first relapse (p = 0.0367). GA 40 mg was well tolerated, with an overall safety profile similar to that of 20 mg. Some features of injection site reactions and immediate postinjection reactions were more common and severe with the higher dose. Conclusions: Glatiramer acetate (GA) 40 mg was safe and well tolerated. The overall efficacy results suggested that a 40-mg dose of GA may be more effective than the currently approved 20-mg daily dose in reducing MRI activity and clinical relapses.
Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

Abstract Objectives. Patients with chronic heart failure (CHF) have an exaggerated immune response, endothelial damage/dysfunction, and increased risk of diabetes mellitus (DM). The inter-relationship(s) between indices of complement activation (soluble membrane attack complex, sMAC), inflammation (hsCRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment, HOMA) in a prospective study including a total of 193 patients with CHF, and assessed whether high levels of these biomarkers had a prognostic impact. Biomarker levels in CHF patients were compared to 100 age-matched controls. Results. Plasma sMAC levels were elevated in patients with CHF due to ischemic heart disease (IHD) as compared with CHF patients with non-ischemic ethiology (p=0.02), but were not predictive of survival or progression of CHF. A moderate strong relation between sMAC and sEsel levels was found β=0.33 (p<0.01), independently of IR and of the presence of DM. In addition, IR was an independent predictor of sMAC in the CHF group β=0.37 (p<0.0001). Conclusions. Independent associations between sMAC, sEsel and IR were found in the CHF patients and we hypothesize that IR leading to endothelial activation results in activation of the complement system and thus damaging of the heart tissue.