julilili42/papers huggingface dataset:
RNA Eluting Surfaces for the Modulation of Gene Expression as a Novel Stent Concept
2017-02-03

Objectives: A new era of drug eluting stents (DESs) is in progress to improve late adverse effects like neointimal hyperplasia after coronary stent implantation in atherosclerotic vessels. Gene expression modulating stents might have the potential as a new promising therapeutic strategy releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall for better regeneration and inhibition of adverse effects.
Methemoglobin Formation in Erythrocytes Stored for Different Time Periods during Extracorporeal Circulation
2017-02-03

Objectives: Erythrocyte concentrates are often needed in extracorporeal circulation (ECC) procedures. Since ECC [e.g., heart-lung machine (HLM) or extracorporeal life support (ECLS)] is routinely applied, we asked whether a 6 hour lasting HLM treatment has an influence on the quality of erythrocytes dependent on their previous storage period at 4°C.
Left-Ventricular-Assist-Device Weaning Protocol Including Exercise and Invasive Hemodynamics - Multi-Institutional Experience
2017-02-03

Background: The possibility of weaning from implantable left ventricular assist devices is excellent treatment alternative for end-stage heart failure patients. This is a feasible possibility especially for patients suffering from end-stage heart failure due to myocarditis.
Application of In Vitro Transcribed Messenger RNA for Cellular Engineering and Reprogramming after Myocardial Infarction
2017-02-03

Objectives: The exogenous delivery of in vitro transcribed (IVT) messenger RNA (mRNA) offers various possibilities for regeneration of infarcted myocardium. Using IVT mRNA, somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated into desired cell types or they can be even used to perform transdifferentiation. Here, we examined the generation of iPSCs using IVT mRNA and performed transdifferentiation experiments.
Out-of-Center ECLS Implantation: Extended Experience of an Interdisciplinary Team Approach
2017-02-03

Background: Extracorporeal life support (ECLS) is an established treatment option for patient in refractory cardiogenic shock. This study describes the outcome of patients who treated with ECLS in cardiogenic shock at remote hospitals.
H1‐antihistamine‐refractory chronic spontaneous urticaria: it's worse than we thought – first results of the multicenter real‐life AWARE study
2017-02-04

Summary Background Most data on chronic spontaneous urticaria ( CSU ) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World‐wide Antihistamine‐Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real‐life setting. Objective To describe the baseline characteristics of the first 1539 German AWARE patients with H1‐antihistamine‐refractory CSU . Methods This prospective non‐interventional study included patients (18–75 years) with a diagnosis of H1‐antihistamine‐refractory CSU for &gt; 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index ( DLQI ), chronic urticaria QoL questionnaire ( CU ‐Q 2 oL), and angioedema QoL questionnaire ( AE ‐QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. Results Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m 2 , respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria ( CI ndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second‐generation H1‐antihistamines (46.3%), first‐generation H1‐antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI , total CU ‐Q 2 oL, and total AE ‐QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%). Conclusions and Clinical Relevance This study reveals that German H1‐antihistamine‐refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CI ndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.
Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks
2017-02-04

ABSTRACT Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O 2 concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. Isolates originating from freshwater habitats are all members of the Betaproteobacteria , while isolates from marine habitats belong almost exclusively to the Zetaproteobacteria . So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing Zetaproteobacteria that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe 2+ in the porewater). The two novel Zetaproteobacteria share characteristic physiological properties of the Zetaproteobacteria group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated Zetaproteobacteria , they produce twisted stalks. We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). The Fe minerals in the stalks were identified as lepidocrocite and possibly ferrihydrite. Immobilization experiments with Ni 2+ showed that the stalks can function as a sink for trace metals. Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle. IMPORTANCE So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the Zetaproteobacteria exist, and most isolates were obtained from habitats containing elevated Fe concentrations. Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. The two novel isolates of Zetaproteobacteria that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. This increases the knowledge about possible habitats in which Zetaproteobacteria can exist. Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. We also showed that the organo-mineral structures can function as a sink for trace metals.
SOCS3 genetic variants and promoter hypermethylation in patients with chronic hepatitis B
2017-02-04

The clinical manifestations of hepatitis B viral infection (HBV) include chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The contribution of negative regulator suppressor of cytokine signaling-3 (SOCS3) promoter variants in HBV disease and SOCS3 hypermethylation in tumor tissues were investigated. The SOCS3 promoter region was screened for polymorphisms in 878 HBV patients and in 272 healthy individuals. SOCS3 promoter methylation was examined by bisulfite sequencing. SOCS3 mRNA expression was quantified in 37 tumor and adjacent non-tumor liver tissue specimens. The minor allele rs12953258A was associated with increased susceptibility to HBV infection (OR=1.3, 95%CI=1.1-1.6, adjusted P=0.03). The minor allele rs111033850C and rs12953258A were observed in increased frequencies in HCC and LC patients compared to CHB patients (HCC: OR=1.7, 95%CI=1.1-2.9, adjusted P=0.046; LC: OR=1.4, 95%CI=1.1-1.9, adjusted P=0.017, respectively). HBV patients with rs111033850CC major genotype had decreased viral load (P=0.034), whereas the rs12953258AA major genotype contributed towards increased viral load (P=0.029). Tumor tissues revealed increased hypermethylation compared to adjacent non-tumor tissues (OR=5.4; 95%CI= 1.9-17.1; P=0.001). Increased SOCS3 expression was observed in HBV infested tumor tissues than non-HBV related tumor tissues (P=0.0048). SOCS3 promoter hypermethylation was associated with relatively low mRNA expression in tumor tissues (P=0.0023). In conclusion, SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development.
Immunotherapeutic strategies for the treatment of renal cell carcinoma: Where will we go?
2017-02-04

Historically, renal cell carcinoma (RCC) is considered a chemotherapy-resistant tumor. The cornerstone of systemic therapy included mammalian target of rapamycin (mTOR) inhibitors, endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Currently, a new era is enteres with promising immunotherapeutic treatments, which are becoming commercially available. Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy - IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules. We will also discuss their mechanism of action and toxicity, the importance of developing new patient selection algorithms (immunoprofiling, guidelines updates) and new biomarkers such as PD-1 expression. Expert commentary: Immunotherapy shows promise, and the current tools used in clinical practice, including guidelines, staging-classification and algorithms should be revised and adapted to the new immunotherapeutic drugs. Although immunotherapy in RCC show promising results, more research is needed in parallel to discover biomarkers that enable the prediction of a treatment response and therefore lead to better patient selection.
Problems on Finite Automata and the Exponential Time Hypothesis
2017-02-05

We study several classical decision problems on finite automata under the (Strong) Exponential Time Hypothesis. We focus on three types of problems: universality, equivalence, and emptiness of intersection. All these problems are known to be CoNP-hard for nondeterministic finite automata, even when restricted to unary input alphabets. A different type of problems on finite automata relates to aperiodicity and to synchronizing words. We also consider finite automata that work on commutative alphabets and those working on two-dimensional words.
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia
2017-02-06

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
Denosumab treatment in the management of patients with advanced prostate cancer: clinical evidence and experience
2017-02-06

Osteoprotective therapies have become an essential component in the management of advanced prostate cancer (PC) patients as bone metastases (BMs) have a major impact on morbidity and mortality. Denosumab is a fully humanized antibody targeting the receptor activator of nuclear factor κB ligand (RANKL), which has been approved by the European Medicines Agency (EMA) in Europe and the United States (US) Food and Drug Administration (FDA) in the US for prevention of skeletal-related events (SREs) in patients with solid tumors and BMs, including PC. The clinical settings in which PC patients should be treated with denosumab are still discussed controversially. In a phase III study, denosumab significantly delayed SREs compared with zoledronic acid (ZA) in patients with metastatic castration-resistant PC (CRPC). In addition, denosumab showed superior effects on pain and health-related quality of life (QoL) in these patients. In patients with nonmetastatic CRPC, denosumab has been proven to significantly increase bone metastases-free survival. However, no significant benefits on cancer-specific and overall survival were observed and denosumab was not approved by the US FDA and EMA in this context. The effectiveness of denosumab in patients with castration-sensitive PC (CSPC) and BMs is also under discussion, as clinical trials with ZA in these patients have not shown significant benefits. Clinical data on the use of denosumab in CSPC are urgently needed.
Effect Analysis Using Nonlinear Structural Equation Mixture Modeling
2017-02-06

In this article, we present an approach for comprehensive analysis of the effectiveness of interventions based on nonlinear structural equation mixture models (NSEMM). We provide definitions of average and conditional effects and show how they can be computed. We extend the traditional moderated regression approach to include latent continous and discrete (mixture) variables as well as their higher order interactions, quadratic or more general nonlinear relationships. This new approach can be considered a combination of the recently proposed EffectLiteR approach and the NSEMM approach. A key advantage of this synthesis is that it gives applied researchers the opportunity to gain greater insight into the effectiveness of the intervention. For example, it makes it possible to consider structural equation models for situations where the treatment is noneffective for extreme values of a latent covariate but is effective for medium values, as we illustrate using an example from the educational sciences.
Surface forms trump underlying representations in functional generalisations in speech perception: the case of German devoiced stops
2017-02-06

Listeners can adapt their perceptual categories for speech sounds in response to speakers' unusual pronunciations. The present study tested whether this generalisation is sensitive to surface or underlying properties of speech by exploiting the devoicing of voiced stops in German. This allows us to assess whether learning on phonetically voiceless stops that are underlyingly voiced generalises to stops that share the same surface form (i.e. voiceless) or the same underlying representation (i.e. voiced). Our results showed only minimal generalisation: learning for (surface) voiceless stops in offset position that are underlyingly voiced generalises to surface and underlying voiceless stops in the same position but neither to voiced nor voiceless stops in intervocalic position. This suggests that listeners extract segments of sufficient acoustic similarity from the input and use them for generalisation of learning in speech perception. The units of perception thereby appear context sensitive rather than abstract phonemes or phonological/articulatory features.
Direct dark matter search with the CRESST experiment
2017-02-06

The quest for the particle nature of dark matter is one of the big open questions of modern physics.A well motivated candidate for dark matter is the so-called WIMP -a weakly interacting massive particle.Recently several theoretically well-motivated models with dark matter candidates in a mass region below the WIMP mass-scale gained also a lot of interest, theoretically and experimentally.The CRESST II experiment located at the Gran Sasso laboratory in Italy is optimised for the detection of the elastic scattering of these low-mass dark matter particles with ordinary matter.We show the results obtained with an improved detector setup with increased radio purity and enhanced background rejection and the results obtained with a dedicated low-threshold analysis of a single conventional detector module.The limit achieved is the most stringent limit achieved for direct dark matter experiments in the mass region below 1.8 GeV/c 2 .We will discuss the expected performance for new small CRESST-type detectors to be used during the next data taking phase.We conclude with an outlook of the future potential for direct dark matter detection using further improved CRESST CaWO 4 cryogenic detectors.
Childhood cancer predisposition syndromes—A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology
2017-02-07

Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected.
Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men
2017-02-07

Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis.
Central Nervous Insulin Administration before Nocturnal Sleep Decreases Breakfast Intake in Healthy Young and Elderly Subjects
2017-02-07

Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m<sup>2</sup>) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m<sup>2</sup>) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat <i>ad libitum</i>. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, <i>p</i> = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, <i>p</i> = 0.0080). This effect was not dependent on sex or age (all <i>p</i> > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery that extends across sleep and might be of particular relevance for potential therapeutic applications.