Miracle-dz/UniFAR-FTUs huggingface dataset:
Different Types of Coagulase Are Associated With 28-Day Mortality in Patients With Staphylococcus aureus Bloodstream Infections

Background: Staphylococcus aureus (S. aureus), a leading cause of bacteremia and infective endocarditis, exploits the human coagulation system by using a wide range of specific virulence factors. However, the impact of these host-pathogen interactions on the outcome of patients with Staphylococcus aureus bacteremia (SAB) remains unclear. Methods: A total of 178 patients with S. aureus bacteremia were included and analyzed regarding bacterial factors (coa gene size, vWbp, clfA, clfB, fnbA, fnbB, fib) and clinical parameters. A stepwise multivariate Cox regression model and a Partitioning Around Medoids (PAM) cluster algorithm were used for statistical analysis. Results: Patients' risk factors for 28-day mortality were creatinine (OR 1.49, p < 0.001), age (OR 1.9, p < 0.002), fibrinogen (OR 0.44, p < 0.004), albumin (OR 0.63, p < 0.02), hemoglobin (OR 0.59, p < 0.03), and CRP (OR 1.72, p < 0.04). Five distinct bacterial clusters with different mortality rates were unveiled, whereof two showed a 2-fold increased mortality and an accumulation of specific coagulase gene sizes, 547-base pairs and 660-base pairs. Conclusions: Based on the data obtained in the present study an association of coagulase gene size and fib regarding 28-day mortality was observed in patients with S. aureus bloodstream infections. Further animal and prospective clinical studies are needed to confirm our preliminary findings.
Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction

Erectile dysfunction (ED) is becoming an increasingly common problem and although oral therapies offer first‐line treatment for many men, they are contraindicated or ineffective in substantial groups of patients. Intracavernosal injection (ICI) therapy is the most effective nonsurgical treatment for ED and offers an effective alternative to oral therapy. Sufficient arterial blood supply and a functional veno‐occlusive mechanism are prerequisites in the attainment and maintenance of a functional erection. Invicorp® (Plethora Solutions, London, UK) is a combination of vasoactive intestinal polypeptide (VIP) 25 µg and phentolamine mesylate 1 or 2 mg for ICI in the management of moderate to severe ED. The two active components have complementary modes of action; VIP has a potent effect on the veno‐occlusive mechanism, but little effect on arterial inflow, whereas phentolamine increases arterial blood flow with no effect on the veno‐occlusive mechanism. Clinical studies showed that Invicorp is effective in ≥80% of men with ED, including those who have failed to respond to other therapies and, unlike existing intracavernosal therapies, is associated with a very low incidence of penile pain and virtually negligible risk of priapism. We estimate that there are >5.9 million men in the USA alone for whom oral ED drugs are not a viable treatment option, and for whom Invicorp might offer a safe and effective alternative.
State of the Market: A Review of Ambulatory Blood Pressure Monitoring Devices

Abstract The introduction of 24-hour ambulatory blood pressure measurement into clinical practice created a large market for ambulatory blood pressure measurement devices. Forty-three such devices from 31 manufacturers or suppliers are now available to satisfy a market demand that is likely to increase. The aim of this article is to identify the devices available and then to examine critically any validation studies assessing accuracy and performance. Of the 43 devices available 18 have been validated according to the protocols of the Association for the Advancement of Medical Instrumentation (AAMI) or the British Hypertension Society (BHS) in 25 reported studies. In 9 of these studies the protocol was not adhered to, and the results, which are therefore questionable, are noted but not considered further. Fourteen devices were evaluated according to the accuracy criteria of both protocols, and of these 9 fulfilled the requirements. From this review of 43 devices on the market it may be concluded that, at the time of writing, there is published evidence for only 9 devices meeting the generally accepted AAMI and BHS criteria for accuracy and performance; these are the A&D TM-2420 models 6 and 7 and TM-2421, CH-Druck, Nissei ABPM DS-240, Profilomat, QuietTrak, and SpaceLabs SL-90202 and SL-90207.
Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats.

The pharmacokinetics, biodisposition, and neuromuscular blocking properties of 3-desacetylvecuronium were studied in 17 adult cats. Animals were divided into three groups: five cats with kidney failure induced by bilateral ligation of the renal pedicles, six cats with galactosamine-induced fulminant hepatitis, and six control cats. An intravenous bolus of 300 micrograms.kg-1 of 3-desacetylvecuronium was rapidly injected into the jugular vein. Arterial blood, urine, and bile samples were collected at regular intervals for 6 h in control cats and for 8 h in cats with kidney or liver failure. The liver was excised for analysis at the end of the experiment. In cats with renal failure, 3-desacetylvecuronium pharmacokinetic and pharmacodynamic variables did not differ from those in control cats. In cats with liver failure, plasma clearance was significantly less and mean residence time greater than in control cats (2.8 +/- 0.6 vs. 14.1 +/- 6.5 ml.kg-1.min-1 and 334 +/- 225 vs. 49 +/- 29 min, mean +/- SD, respectively). Volume of distribution at steady state in cats with liver failure and in control cats was not different. Also, in cats with liver failure, the duration of action and recovery index of 3-desacetylvecuronium was significantly greater than in control cats (168 +/- 62 vs. 82 +/- 32 min, and 39 +/- 19 vs. 10 +/- 4 min, respectively). Onset time of neuromuscular blockade was similar in all three groups. Total recovery of 3-desacetylvecuronium, for all three groups, in urine, bile, and liver was 90 +/- 11% (mean +/- SD). In control cats, 70 +/- 18% of 3-desacetylvecuronium was recovered in bile and liver and 19 +/- 14% in urine. No 3,17-bidesacetylvecuronium (a putative 3-desacetylvecuronium metabolite) was detected. (ABSTRACT TRUNCATED AT 250 WORDS)
Perceptions of the Self Versus One’s Own Social Group: (Mis)conceptions of Older Women’s Interest in and Competence With Technology

Our analysis investigates how gender, age, and technology stereotypes relate to one another and how this relationship reinforces or questions stereotypes. Based on intersectionality, stereotyping, and sense-making literature, our study explores how older women perceive their own interest in and competence with technology and that of their peers. We conducted qualitative in-depth interviews with women between 65 and 75 years of age in Germany. Our findings indicate that their evaluations of others are age and gender stereotyped. When explaining their own interest in technology, they refer to their individual preferences, and for explaining their own competence of technology, they refer to social categories. Plus, assumptions of technology usage seem to be gendered. On the basis of our findings, we discuss the need for taking social categories into account when evaluating inclusiveness with new technologies.
A hybrid technology acceptance approach for exploring e-CRM adoption in organizations

Customer relationship management (CRM) is replacing the traditional ‘four Ps’ of marketing – product, price, place and promotion. Forging long-term relationships with customers is the key to stability in an increasingly dynamic market. Despite the steady growth in the number of worldwide installations, industry studies indicate that approximately 60% of web-based CRM software (e-CRM) installations are failures. System use is recognized as one of the important indicators for successful implementation of information systems (IS) and is often correlated with other constructs, such as user attitude and behavioral intention, in the literature. The technology acceptance model (TAM) is particularly useful for explaining and analyzing IS-usage behavior and subsequently, the behavior is influenced by attitude and behavioral intention. However, TAM is incomplete for either considering only part of the attributes of the innovation factor or only part of the factors affecting IS innovation process. Therefore, this study integrates TAM with an extension of innovation diffusion theory (IDT), IS innovation model, in a complimentary manner and, furthermore, empirically concludes some guidelines for practitioners to effectively assist in the diffusion of e-CRM in organizations.
An Efficient Ant Colony System for Edge Detection in Image Processing

Edge detection is a fundamental procedure in image processing, machine vision, and computer vision. Its application area ranges from astronomy to medicine in which isolating the objects of interest in the image is of a significant importance. However, performing edge detection is a non-trivial task for which a large number of techniques have been proposed to solve it. This paper investigates the use of Ant Colony Optimization — a prominent set of optimization heuristics — to solve the edge detection problem. We propose two modified versions of the algorithm Ant Colony System (ACS) for an efficient and a noise-free edge detection.
Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury

Introduction: Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and without neuroimaging findings (CT and MRI). Material and Methods: Within 24 h of a mTBI, determined by a Glasgow Coma Scale (GCS) between 13 and 15, participants (n = 250) underwent a computed tomography (CT) and magnetic resonance imaging (MRI) scan and provided a blood sample. Participants were classified into three groups according to imaging findings; (1) CT+, (2) MRI+ (CT–), (3) Controls (CT– MRI–). Plasma levels of circulating cytokines (IL-6, IL-10, TNFα), and vascular endothelial growth factor (VEGF) were measured using an ultra-sensitive immunoassay. Results: Concentrations of inflammatory cytokines (IL-6, TNFα) and VEGF were elevated in CT+, as well as MRI+ groups (p < 0.001), compared to controls, even after controlling for age, sex and cardiovascular disease (CVD)-related risk factors; hypertension, and hyperlipidemia. Post-concussive symptoms were associated with imaging groupings, but not inflammatory cytokines in this cohort. Levels of VEGF, IL-6, and TNFα differentiated patients with CT+ findings from controls, with the combined biomarker model (VEGF, IL-6, TNFα, and IL-10) showing good discriminatory power (AUC 0.92, 95% CI 0.87–0.97). IL-6 was a fair predictor of MRI+ findings compared to controls (AUC 0.70, 95% CI 0.60–0.78). Finally, the combined biomarker model discriminated patients with MRI+ from CT+ with an AUC of 0.71 (95% CI 0.62–0.80). Conclusions: When combined, IL-6, TNFα, and VEGF may provide a promising biomarker cytokine panel to differentiate mTBI patients with CT+ imaging vs. controls. Singularly, IL-6 was a fair discriminator between each of the imaging groups. Future research directions may help elucidate mechanisms related to injury severity and potentially, recovery following an mTBI.
Age and Immune Response in Organ Transplantation

The immune system undergoes a complex and continuous remodeling as the result of aging. These changes have a major impact on allorecognition and alloresponse. In addition, immunosuppression in the elderly is challenging as a consequence of an increased incidence of associated comorbidities and altered pharmacokinetics. Both advanced donor and recipient age should be considered independent risk factors for poor patient and graft survival rates, albeit acting in a synergistic manner. Consequently, modifications of the immune system because of aging may request an age-adapted allocation and immunosuppression in parallel with close patient monitoring. Interventions to selectively target changes associated with the senescence process seem to be promising therapeutic strategies to improve transplantation outcome. Here, we are going to review the immunologic changes associated with the aging process relevant for transplantation and their impact on immunosuppressive protocols, organ allocation policies, and transplantation outcome.
A novel biomaterial for osteotropic drug nanocarriers: synthesis and biocompatibility evaluation of a PLGA-ALE conjugate.

BACKGROUND & AIMS Osteotropic drug-delivery systems have been proposed as a means to provide drugs with affinity to bone tissues. Drugs or proteins have been linked chemically to bone-seeking agents, such as bisphosphonates (BPs); alternatively, drug-loaded nanoparticles have been used to target specific tissues, such as tumor areas. In our current research, these approaches were merged by synthesizing a novel bone-seeking polymer conjugate, from which targetable nanoparticles can be produced. MATERIALS & METHODS An amino-BP, alendronate (ALE) was bound covalently to a biodegradable polymer, poly(lactic-co-glycolide) (PLGA), containing a free end carboxylic group. Blood compatibility and cytotoxicity were assessed in vitro. RESULTS & DISCUSSION By a classical solvent-evaporation method, nanoparticles with a mean size of 200-300 nm were prepared from the conjugate; sterilization was achieved by gamma-irradiation, confirming their potential as injectable drug nanocarriers. Owing to the presence of the BP residue, PLGA-ALE nanoparticles were adsorbed onto hydroxyapatite to a higher extent than pure PLGA nanoparticles. The PLGA-ALE conjugate did not induce either hemolysis or alterations of the plasmatic phase of coagulation, or cytotoxic effects on endothelial cells and trabecular osteoblasts. CONCLUSION The prepared conjugate represents a novel biomaterial that is able to provide nanoparticles, which can be further loaded with drugs, such as anticancer agents, and addressed to osteolytic or other bone diseases.
Huntington's disease: progress and potential in the field

While the first description of Huntington's disease was reported over a century ago, no therapy exists that can halt or ameliorate the inexorable disease progression. Tremendous progress, however, has been made in significantly broadening the understanding of pathogenic mechanisms in this neurological disorder that may eventually lead to successful treatment strategies. Huntington's disease is caused by the expansion of a CAG repeat in the huntingtin gene, which results in the expression of a mutant form of the protein that is toxic to neurons. Several mechanisms have been identified in mediating this toxicity, such as protein aggregation, mitochondrial dysfunction, oxidative stress, transcriptional dysregulation, aberrant apoptosis, altered proteosomal function and excitotoxicity. With increasing understanding of each of these pathogenic mechanisms, therapeutic strategies have attempted to target specific aspects of each. There have been many encouraging reports of preclinical efficacy in transgenic Huntington's disease mice, from which a number have been extended to human clinical trials with some success. This review focuses on these studies and the compounds that hold promise for treating human Huntington's disease.
Cell-Based Radiotracer Binding and Uptake Inhibition Assays: A Comparison of In Vitro Methods to Assess the Potency of Drugs That Target Monoamine Transporters

High-affinity monoamine transporters are targets for prescribed medications and stimulant drugs of abuse. Therefore, assessing monoamine transporter activity for candidate medications and newly-emerging drugs of abuse provides essential information for industry, academia, and public health. Radiotracer binding and uptake inhibition are the gold standard assays for determining drug–transporter interaction profiles. The combined results from such assays yield a unique biochemical fingerprint for each compound. Over time, different assay methods have been developed to assess transporter activity, and the comparability of data across various assay platforms remains largely unclear. Here, we compare the effects of six well-established stimulants in two different cell-based uptake inhibition assays, one method using adherent cells and the other using suspended cells. Furthermore, we compare the data from transfected cell lines derived from different laboratories and data reported from rat synaptosomes. For transporter inhibitors, IC50 values obtained by the two experimental methods were comparable, but using different transfected cell lines yielded disparate results. For transporter substrates, differences between the two cell lines were less pronounced but the drugs displayed different inhibition potencies when evaluated by the two methods. Our study illustrates the inherent limitations when comparing transporter inhibition data from different laboratories and stresses the importance of including appropriate control experiments with reference compounds when investigating new drugs of interest.
Mechanisms Involved in the Progressive Pressor Response to Very Small Amounts of Angiotensin in Conscious Rabbits

The cause of the progressive pressor response to small amounts of angiotensin in the conscious rabbit has been studied by examination of the possible role of the adrenal glands, sodium and water balance, and sympathetic nervous influences. No evidence has been discovered to implicate adrenal hormone stimulation or renal sodium and water retention in the progressive enhancement of pressor sensitivity which can be observed at angiotensin infusion rates up to about 0.1 μg/kg/min; and at higher infusion rates sodium and water loss seems to supply an opposing stimulus, tending to prevent the full development of progressively increasing pressor response. The progressive pressor response to angiotensin was almost completely prevented by adrenergic neuron blockade. This suggested that an important action of small amounts of angiotensin might be mediated by the autonomic nervous system, and evidence is given for the possibility that angiotensin may act by constricting the vascular supply to the hind-brain vasomotor control centers, thus allowing a progressive pressor response to develop by systemic baroreceptor resetting.
Integrated Analysis of Metabolite and Transcript Levels Reveals the Metabolic Shifts That Underlie Tomato Fruit Development and Highlight Regulatory Aspects of Metabolic Network Behavior1[W]

Tomato (Solanum lycopersicum) is a well-studied model of fleshy fruit development and ripening. Tomato fruit development is well understood from a hormonal-regulatory perspective, and developmental changes in pigment and cell wall metabolism are also well characterized. However, more general aspects of metabolic change during fruit development have not been studied despite the importance of metabolism in the context of final composition of the ripe fruit. In this study, we quantified the abundance of a broad range of metabolites by gas chromatography-mass spectrometry, analyzed a number of the principal metabolic fluxes, and in parallel analyzed transcriptomic changes during tomato fruit development. Metabolic profiling revealed pronounced shifts in the abundance of metabolites of both primary and secondary metabolism during development. The metabolite changes were reflected in the flux analysis that revealed a general decrease in metabolic activity during ripening. However, there were several distinct patterns of metabolite profile, and statistical analysis demonstrated that metabolites in the same (or closely related) pathways changed in abundance in a coordinated manner, indicating a tight regulation of metabolic activity. The metabolite data alone allowed investigations of likely routes through the metabolic network, and, as an example, we analyze the operational feasibility of different pathways of ascorbate synthesis. When combined with the transcriptomic data, several aspects of the regulation of metabolism during fruit ripening were revealed. First, it was apparent that transcript abundance was less strictly coordinated by functional group than metabolite abundance, suggesting that posttranslational mechanisms dominate metabolic regulation. Nevertheless, there were some correlations between specific transcripts and metabolites, and several novel associations were identified that could provide potential targets for manipulation of fruit compositional traits. Finally, there was a strong relationship between ripening-associated transcripts and specific metabolite groups, such as TCA-cycle organic acids and sugar phosphates, underlining the importance of the respective metabolic pathways during fruit development.
Banking on Reciprocity: Deposit Insurance and Insolvency

There is an empirical connection between deposit insurance, risktaking, and insolvency. We argue that if banks maximize profit this amounts to a puzzle (even taking into account that deposit insurance decreases incentives for customers to monitor bankers). However, we show that the empirical regularities can be well captured if bankers are motivated by reciprocity towards their customer base.
Intensive agriculture reduces soil biodiversity across Europe

Soil biodiversity plays a key role in regulating the processes that underpin the delivery of ecosystem goods and services in terrestrial ecosystems. Agricultural intensification is known to change the diversity of individual groups of soil biota, but less is known about how intensification affects biodiversity of the soil food web as a whole, and whether or not these effects may be generalized across regions. We examined biodiversity in soil food webs from grasslands, extensive, and intensive rotations in four agricultural regions across Europe: in Sweden, the UK, the Czech Republic and Greece. Effects of land‐use intensity were quantified based on structure and diversity among functional groups in the soil food web, as well as on community‐weighted mean body mass of soil fauna. We also elucidate land‐use intensity effects on diversity of taxonomic units within taxonomic groups of soil fauna. We found that between regions soil food web diversity measures were variable, but that increasing land‐use intensity caused highly consistent responses. In particular, land‐use intensification reduced the complexity in the soil food webs, as well as the community‐weighted mean body mass of soil fauna. In all regions across Europe, species richness of earthworms, Collembolans, and oribatid mites was negatively affected by increased land‐use intensity. The taxonomic distinctness, which is a measure of taxonomic relatedness of species in a community that is independent of species richness, was also reduced by land‐use intensification. We conclude that intensive agriculture reduces soil biodiversity, making soil food webs less diverse and composed of smaller bodied organisms. Land‐use intensification results in fewer functional groups of soil biota with fewer and taxonomically more closely related species. We discuss how these changes in soil biodiversity due to land‐use intensification may threaten the functioning of soil in agricultural production systems.