Circulating microRNAs as biomarkers - True Blood?

MicroRNAs are post-transcriptional regulators that are involved in many physiological and pathophysiological conditions. A recent study compared the expression profiles of hundreds of blood-borne microRNAs across a variety of nonmalignant and malignant diseases to identify disease-specific expression patterns. The resulting microRNA expression data could be used to discriminate disease samples with a high level of accuracy, demonstrating the potential for using microRNA signatures for the blood-based diagnosis of disease

Stress and heat flux via automatic differentiation

Machine-learning potentials provide computationally efficient and accurate approximations of the Born-Oppenheimer potential energy surface. This potential determines many materials properties and simulation techniques usually require its gradients, in particular forces and stress for molecular dynamics, and heat flux for thermal transport properties. Recently developed potentials feature high body order and can include equivariant semi-local interactions through message-passing mechanisms. Due to their complex functional forms, they rely on automatic differentiation (AD), overcoming the need for manual implementations or finite-difference schemes to evaluate gradients. This study demonstrates a unified AD approach to obtain forces, stress, and heat flux for such potentials, and provides a model-independent implementation. The method is tested on the Lennard-Jones potential, and then applied to predict cohesive properties and thermal conductivity of tin selenide using an equivariant message-passing neural network potential.Comment: 9 pages, 2 figures, 6 tables, excluding supplement (3 pages, 3 figures, 2 tables). Additional information at https://marcel.science/gl

Buergerversicherung vs. Gesundheitspraemie – Vergleich der Reformoptionen zur Finanzierung der Gesetzlichen Krankenversicherung

The wage-dependence of the Public Health Insurance (PHI) as well as the somewhat inconsistent parallel coverage via PHI and private health insurance constitute drawbacks of the present health care revenue system, leading to undesirable distributional and allocative patterns and disadvantages in the course of demographic and economic change. Two conflicting approaches, the “Buergerversicherung” (“Citizens’ Health Insurance”) and the “Gesundheitsprämie” (“Flat Rate Health Insurance”) try to remedy these by way of different methods – the former with a statutory health insurance for all and a comprehensive income basis for proportionate health insurance contributions, the latter with a flat rate contribution for the present PHI including a massive tax subsidy for the contributions for low-income groups and children. The paper presents simulations of the distributional effects. Differing effects become evident. Moreover these patterns also reflect different “philosophies” of social welfare and public revenue regimes. The “Bürgerversicherung” reduces payments by wage and wage-replacement earners and generally by low income groups, the “Gesundheitspraemie” favors higher-income individuals and particularly two-earner married couples.Social Health Insurance System, Public Finance

Zuzahlungen nach dem GKV-Modernisierungsgesetz (GMG) unter Beruecksichtigung von Haertefallregelungen

The law for the Modernisation of the Social Health Insurance System 2003 ("GKV-Modernisierungsgesetz – GMG" 2003) provides, among other measures, for a noticeable increase in co-payments and also for a reduction of possibilities for claiming exemptions from co-payments. Against this backdrop, the authors of the paper present, at the start, the varying news on co-insurance payments held by different political groups. Thereafter, the theoretical foundations of co-payments are described. Finally, on the basis of extensive empirically founded computations, the effects of the new co-payment rules (together with relevant new exemptions) are compared with the effects of the rules still in force.Social Health Insurance System, co-payment, public finance

Exon Array Analysis using re-defined probe sets results in reliable identification of alternatively spliced genes in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Treatment of non-small cell lung cancer with novel targeted therapies is a major unmet clinical need. Alternative splicing is a mechanism which generates diverse protein products and is of functional relevance in cancer.</p> <p>Results</p> <p>In this study, a genome-wide analysis of the alteration of splicing patterns between lung cancer and normal lung tissue was performed. We generated an exon array data set derived from matched pairs of lung cancer and normal lung tissue including both the adenocarcinoma and the squamous cell carcinoma subtypes. An enhanced workflow was developed to reliably detect differential splicing in an exon array data set. In total, 330 genes were found to be differentially spliced in non-small cell lung cancer compared to normal lung tissue. Microarray findings were validated with independent laboratory methods for <it>CLSTN1</it>, <it>FN1</it>, <it>KIAA1217</it>, <it>MYO18A</it>, <it>NCOR2</it>, <it>NUMB</it>, <it>SLK</it>, <it>SYNE2</it>, <it>TPM1</it>, (in total, 10 events) and <it>ADD3</it>, which was analysed in depth. We achieved a high validation rate of 69%. Evidence was found that the activity of FOX2, the splicing factor shown to cause cancer-specific splicing patterns in breast and ovarian cancer, is not altered at the transcript level in several cancer types including lung cancer.</p> <p>Conclusions</p> <p>This study demonstrates how alternatively spliced genes can reliably be identified in a cancer data set. Our findings underline that key processes of cancer progression in NSCLC are affected by alternative splicing, which can be exploited in the search for novel targeted therapies.</p

Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1

Background: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. Methods: In NF1 patients (n = 11; 19-44 years) and healthy controls (HC; n = 11; 19-31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. Results: In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. Conclusions: This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option

Comparative Evaluation of Combined Navigated Laser Photocoagulation and Intravitreal Ranibizumab in the Treatment of Diabetic Macular Edema

Objective: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME). Research Design and Methods: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12. Results: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p=0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 +/- 1.23 vs. 3.88 +/- 2.32, p<=0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p<=0.001). Conclusions: Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies