julilili42/papers huggingface dataset:
Review of mechanisms of deoxynivalenol‐induced anorexia: The role of gut microbiota
2017-05-03

Abstract Deoxynivalenol (DON) is one of the most important mycotoxins in cereal‐based foods or other food productions, produced by Fusarium species . Because of the high occurrence of DON in food combined with vast consumption of cereals and grain worldwide, the DON‐contaminated food is a very harmful factor for human and animal health. DON has been reported to induce anorexia at lower or chronic doses in animal models. However, further researches for DON‐induced anorexia are limited. Previous publications demonstrated a close link between Bacteroidetes and Firmicutes , two kinds of gut microbiota, with weight loss and the effect of low administration of DON on neurotransmitters in the frontal cortex, cerebellum, hypothalamus, hippocampus and pons/medulla. These data are similar to other studies, which show selective 5HT α receptor agonists apparently causing hyperphagia whereas 5HT 1β agonists appear to induce anorexia. Thus, the neurochemical effects of lower DON exposure can be as a result of peripheral toxicological events such as emesis, which overwhelmed its more subtle feed refusal activity. Besides, changes in the microbiota have an impact on stress‐related behaviors like anxiety and depression, which can lead to weight loss through decreased feed intake. Gut dysbiosis is also associated with brain dysfunction and with behavioral changes. These conclusions illustrate as well a potential explanation for DON‐induced anorexia.In this review, we summarize information about DON‐induced anorexia from previous studies and provide our opinion for future investigations that could establish a link between gut microbiota, neurotransmitters, anorexia and weight loss under the DON exposure. Copyright © 2017 John Wiley &amp; Sons, Ltd.
Objective audiometry with DPOAEs
2017-05-03

Compared to conventional DPOAE and TEOAE methods, separation of DPOAE components using short-pulse DPOAEs in combination with optimized stimulus parameters considerably enhances the accuracy of DPOAEs for diagnosing impairment of the cochlear amplifier.
Animal Rights and Robot Ethics
2017-05-03

This paper investigates challenges which anthropocentric and pathocentric ethics have to face when confronted with moral considerations about non-human animals, especially so-called disenhanced animals, and a new class of technological artifacts, namely social robots. Referring to the case of animal welfare, robot ethics emerges as a new discipline that has not yet reflected on the ideological biases that commonly underlie moral judgments toward animals and find expression in robot ethics, too. As a consequence, robot ethics perpetuates the “work of purification,” that is, the isolation and definition of a particular entity possessing a moral status. Whenever such an entity is defined, the definition excludes all those entities which could likewise possess a moral status but do not fit exactly to the pre-specified definition. The crucial question, then, is whether to seek an ethic of unconditional compassion that doesn't allow itself to be restricted by ideology and is therefore convenient for animal rights and robot ethics as well.
Stone duality for languages and complexity
2017-05-03

Complexity theory and the theory of regular languages both belong to the branch of computer science where the use of resources in computing is the main focus. However, they operate at different levels. While complexity theory seeks to classify computational problems by resource use, such as space and time, regular language theory remains at the very base of this hierarchy and is concerned with classes of computational problems for which membership is (potentially) decidable.
Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection and Risk in RTS,S/AS01E Vaccinees
2017-05-04

RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.
Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations
2017-05-04

We could not obtain statistically significant evidence for a role of common SLC5A2 variants in the regulation of glucagon release in the fasting state or upon glucose challenge. Moreover, the reported nominal effects of individual SLC5A2 variants on fasting and post-challenge glucose levels may probably not be mediated by altered glucagon release.
Entyloma helianthi: identification and characterization of the causal agent of sunflower white leaf smut
2017-05-04

White leaf smut is a minor foliar disease of sunflower (Helianthus annuus) in the United States. The disease occurs primarily in greenhouse-grown sunflowers in California and causes leaf spot, defoliation, and a reduction in yield and crop value. Historically, many Entyloma specimens with similar morphological characters, but infecting diverse plant genera including Helianthus, were called Entyloma polysporum. Recent comparative morphological and molecular work has shown that Entyloma species infect hosts within a single genus or species, suggesting that the sunflower Entyloma species may not be E. polysporum. In 2015, sunflower leaf smut material was collected from ornamental sunflowers in a greenhouse in Santa Barbara County, California. Morphologically, this species differed from E. polysporum in having smaller, more regular-shaped teliospores and prominently developed conidiophores with cylindrical conidia. The rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]) region of the sunflower leaf smut was phylogenetically distinct from all previously sequenced Entyloma species and found only on H. annuus. This study confirms that the sunflower leaf smut pathogen represents a novel species, Entyloma helianthi. Possible misidentification of the anamorphic stage of Entyloma helianthi as another leaf spot pathogen, Ramularia helianthi, is also discussed.
A Methylidene Group in the Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia‐Lyases
2017-05-04

Abstract Aromatic amino acid ammonia‐lyases and aromatic amino acid 2,3‐aminomutases contain the post‐translationally formed prosthetic 3,5‐dihydro‐4‐methylidene‐5 H ‐imidazol‐5‐one (MIO) group. MIO enzymes catalyze the stereoselective synthesis of α‐ or β‐amino acid enantiomers, making these chemical processes environmentally friendly and affordable. Characterization of novel inhibitors enables structural understanding of enzyme mechanism and recognizes promising herbicide candidates as well. The present study found that both enantiomers of the aminophosphonic acid analogue of the natural substrate phenylalanine and a novel derivative bearing a methylidene at the β‐position inhibited phenylalanine ammonia‐lyases (PAL), representing MIO enzymes. X‐ray methods unambiguously determined the absolute configuration of all tested enantiomers during their synthesis. Enzyme kinetic measurements revealed the enantiomer of the methylidene‐substituted substrate analogue as being a mirror image relation to the natural l ‐phenylalanine as the strongest inhibitor. Isothermal titration calorimetry (ITC) confirmed the binding constants and provided a detailed analysis of the thermodynamic driving forces of ligand binding. Molecular docking suggested that binding of the ( R )‐ and ( S )‐enantiomers is possible by a mirror image packing. magnified image
Modulation of leucocytic angiotensin-converting enzymes expression in patients maintained on high-permeable haemodialysis
2017-05-04

Taken together, these data demonstrate that employment of membranes with high permeability eliminates a spectrum of mediators from circulation that affect the RAS components in leucocytes, especially ACE/ACE2.
Follow‐up of patients with refractory or relapsed multiple myeloma after allogeneic hematopoietic cell transplantation
2017-05-04

Abstract Background The role of allogeneic hematopoietic cell transplantation ( HCT ) for the treatment of multiple myeloma is controversial. However, the introduction of proteasome inhibitors and immunomodulatory drugs might influence outcomes in case of relapse or refractory disease after allogeneic HCT . Methods We report 41 consecutive patients that underwent allogeneic HCT for the treatment of relapsed or refractory multiple myeloma. Results Three‐year event‐free survival ( EFS ) and overall survival ( OS ) of the whole cohort were 15% and 51%, respectively. In a subgroup analysis, allogeneic HCT after a second high‐dose chemotherapy with autologous stem cell support was associated with a decreased 3‐year EFS (6% vs 24%, P =.04) and OS (35% vs 64%, P =.09). In case of relapse or refractory disease after allogeneic HCT , the treatment with proteasome inhibitors or immunomodulatory drugs significantly improved survival (1‐year OS 79% vs 29%, P =.001). Conclusion The incorporation of proteasome inhibitors and immunomodulatory drugs into transplant protocols has the potential to improve outcomes and refine the role of allogeneic HCT for the treatment of multiple myeloma as a platform for long‐term disease control.
Treatment of hyperandrogenism in women with ethinylestradiol and cyproteroneacetate
2017-05-04

In recent years, there has been an important and intensive controversy regarding the thromboembolic risk of hormonal contraceptives containing ethinylestradiol combined with certain progestogens li...
Cover Picture: Luminescent Ni0 Diisocyanide Chelates as Analogues of CuI Diimine Complexes (Chem. Eur. J. 36/2017)
2017-05-04

Photoluminescence at low temperature was observed for the first time from homoleptic Ni0 isocyanide complexes. The observation of luminescence, even though currently restricted to low temperatures, is an important proof-of-concept in the search for earth-abundant alternatives to photoactive complexes made from precious metals. More information can be found in the Communication by O. S. Wenger et al. on page 8577. Photoluminescence at low temperature was observed for the first time from homoleptic Ni0 isocyanide complexes. The observation of luminescence, even though currently restricted to low temperatures, is an important proof-of-concept in the search for earth-abundant alternatives to photoactive complexes made from precious metals. More information can be found in the Communication by O. S. Wenger et al. on page 8577.
Current-Phase Relation of Ballistic Graphene Josephson Junctions
2017-05-05

The current-phase relation (CPR) of a Josephson junction (JJ) determines how the supercurrent evolves with the superconducting phase difference across the junction. Knowledge of the CPR is essential in order to understand the response of a JJ to various external parameters. Despite the rising interest in ultraclean encapsulated graphene JJs, the CPR of such junctions remains unknown. Here, we use a fully gate-tunable graphene superconducting quantum intereference device (SQUID) to determine the CPR of ballistic graphene JJs. Each of the two JJs in the SQUID is made with graphene encapsulated in hexagonal boron nitride. By independently controlling the critical current of the JJs, we can operate the SQUID either in a symmetric or asymmetric configuration. The highly asymmetric SQUID allows us to phase-bias one of the JJs and thereby directly obtain its CPR. The CPR is found to be skewed, deviating significantly from a sinusoidal form. The skewness can be tuned with the gate voltage and oscillates in antiphase with Fabry-Pérot resistance oscillations of the ballistic graphene cavity. We compare our experiments with tight-binding calculations that include realistic graphene-superconductor interfaces and find a good qualitative agreement.
Location and distribution of micro-inclusions in the EDML and NEEM ice cores using optical microscopy and in situ Raman spectroscopy
2017-05-05

Abstract. Impurities control a variety of physical properties of polar ice. Their impact can be observed at all scales – from the microstructure (e.g., grain size and orientation) to the ice sheet flow behavior (e.g., borehole tilting and closure). Most impurities in ice form micrometer-sized inclusions. It has been suggested that these μ inclusions control the grain size of polycrystalline ice by pinning of grain boundaries (Zener pinning), which should be reflected in their distribution with respect to the grain boundary network. We used an optical microscope to generate high-resolution large-scale maps (3 μm pix−1, 8 × 2 cm2) of the distribution of micro-inclusions in four polar ice samples: two from Antarctica (EDML, MIS 5.5) and two from Greenland (NEEM, Holocene). The in situ positions of more than 5000 μ inclusions have been determined. A Raman microscope was used to confirm the extrinsic nature of a sample proportion of the mapped inclusions. A superposition of the 2-D grain boundary network and μ-inclusion distributions shows no significant correlations between grain boundaries and μ inclusions. In particular, no signs of grain boundaries harvesting μ inclusions could be found and no evidence of μ inclusions inhibiting grain boundary migration by slow-mode pinning could be detected. Consequences for our understanding of the impurity effect on ice microstructure and rheology are discussed.
Emotional self–other voice processing in schizophrenia and its relationship with hallucinations: ERP evidence
2017-05-05

Abstract Abnormalities in self–other voice processing have been observed in schizophrenia, and may underlie the experience of hallucinations. More recent studies demonstrated that these impairments are enhanced for speech stimuli with negative content. Nonetheless, few studies probed the temporal dynamics of self versus nonself speech processing in schizophrenia and, particularly, the impact of semantic valence on self–other voice discrimination. In the current study, we examined these questions, and additionally probed whether impairments in these processes are associated with the experience of hallucinations. Fifteen schizophrenia patients and 16 healthy controls listened to 420 prerecorded adjectives differing in voice identity (self‐generated [SGS] versus nonself speech [NSS]) and semantic valence (neutral, positive, and negative), while EEG data were recorded. The N1, P2, and late positive potential (LPP) ERP components were analyzed. ERP results revealed group differences in the interaction between voice identity and valence in the P2 and LPP components. Specifically, LPP amplitude was reduced in patients compared with healthy subjects for SGS and NSS with negative content. Further, auditory hallucinations severity was significantly predicted by LPP amplitude: the higher the SAPS “voices conversing” score, the larger the difference in LPP amplitude between negative and positive NSS. The absence of group differences in the N1 suggests that self–other voice processing abnormalities in schizophrenia are not primarily driven by disrupted sensory processing of voice acoustic information. The association between LPP amplitude and hallucination severity suggests that auditory hallucinations are associated with enhanced sustained attention to negative cues conveyed by a nonself voice.
Maternal metabolism in the fasting state and fetal cardiac activity
2017-05-05

The development of the fetal autonomous nervous system (ANS) can be investigated by heart rate variability (HRV) measured by biomagnetic sensors. We recently showed that fetal HRV is altered after a glucose load in mothers with gestational diabetes. However the effect of maternal metabolism and weight development of the mother on fetal HRV is largely unknown.
Impaired stimulated insulin-processing as predictor of non-response to lifestyle intervention
2017-05-05

Lifestyle intervention (LI) is effective in the prevention of type 2 diabetes. Known predictors of a non-response to LI, i.e. no improvement in glycemia, are insulin resistance and impaired insulin secretion. It is unknown whether impaired insulin-processing also contributes to impaired LI response.
Fiber intake influences the association between variants in TCF7L2 and body weight reduction during a lifestyle intervention and at long-term follow-up
2017-05-05

The extent of weight loss in response to lifestyle intervention (LI) varies considerably between individuals. Gene-diet interactions may explain parts of this difference. The aim of the present study was to evaluate if the TCF7L2 genotype influences the impact of fiber intake on the reduction of body weight during LI and at long-term follow-up.
Central nervous insulin administration before nocturnal sleep decreases breakfast intake in healthy young and elderly subjects
2017-05-05

Studies in animals and humans indicate that peripheral insulin acts on the brain to decrease food intake and body weight. We investigated in young and elderly healthy humans whether central nervous insulin administration before nocturnal sleep, as a period of reduced metabolic activity and largely absent external stimulation, affects eating behavior and energy turnover on the subsequent morning.
The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
2017-05-08

We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD-L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD-1, CD8 and PD-L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of HPV16 DNA/p16 status. The median follow-up was 48 months (range: 4-100). The 2-year-OS was 84.1% for the entire cohort. High PD-1 and PD-L1 expression were more common in patients with positive HPV16 DNA (p < 0.001 and p = 0.008, respectively) and high infiltration by CD8+ TILs (p < 0.001 for both markers). High PD-L1 expression correlated with superior OS (p = 0.025), LPFS (p = 0.047) and DMFS (p = 0.048) in multivariable analysis, whereas no significance could be demonstrated for PD-1. Patients with CD8<sup>high</sup> /PD-L1<sup>high</sup> expression had favorable outcome (p < 0.001 for all endpoints) compared to other groups. We validated the superior OS data on CD8<sup>high</sup> /PD-L1<sup>high</sup> using the Cancer Genome Atlas TCGA dataset (n = 518; p = 0.032). High PD-L1 expression was a favorable prognostic marker in HPV16-negative but not HPV16-positive patients. In conclusion, HPV-positive tumors showed higher expression of immune markers. PD-L1 expression constitutes an independent prognostic marker in SCCHN patients post-adjuvant CRT. In conjunction with CD8 status, these data provide an important insight on the immune contexture of SCCHN and are directly relevant for future treatment stratification with PD-1/PD-L1 immune checkpoint inhibitors to complement CRT.
Eikonal instability of Gauss-Bonnet–(anti-)–de Sitter black holes
2017-05-08

Here we have shown that asymptotically anti-de Sitter (AdS) black holes in\\nthe Einstein-Gauss-Bonnet (GB) theory are unstable under linear perturbations\\nof spacetime in some region of parameters. This (eikonal) instability develops\\nat high multipole numbers. We found the exact parametric regions of the eikonal\\ninstability and extended this consideration to asymptotically flat and de\\nSitter cases. The approach to the threshold of instability is driven by purely\\nimaginary quasinormal modes, which are similar to those found recently in [5]\\nfor the higher curvature corrected black hole with the planar horizon. The\\nfound instability may indicate limits of holographic applicability of the\\nGB-AdS backgrounds. Recently, through the analysis of critical behavior in AdS\\nspace-time in the presence of Gauss-Bonnet term, it was shown [19] that that,\\nif the total energy content of the AdS space-time is small, then no black holes\\ncan be formed with mass less than some critical value. A similar mass gap was\\nalso found when considering collapse of mass shells in asymptotically flat\\nGauss-Bonnet theories [20]. The found instability of all sufficiently small\\nEinstein-Gauss-Bonnet-AdS, -dS and asymptotically flat black holes may explain\\nthe existing mass gaps in their formation.\\n
Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping
2017-05-08

The high genomic instability of non-small cell lung cancer tumors leads to the rapid development of resistance against promising EGFR tyrosine kinase inhibitors (TKIs). A recently detected triple mutation compromises the activity of the gold standard third-generation EGFR inhibitors. We have prepared a set of trisubstituted imidazoles with a rigidized 7-azaindole hinge binding motif as a new structural class of EGFR inhibitors by a target hopping approach from p38α MAPK inhibitor templates. On the basis of an iterative approach of docking, compound preparation, biological testing, and SAR interpretation, robust and flexible synthetic routes were established. As a result, we report two reversible inhibitors 11d and 11e of the clinically challenging triple mutant L858R/T790M/C797S with IC<sub>50</sub> values in the low nanomolar range. Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC<sub>50</sub> value of 1 nM against the EGFR L858R/T790M double mutant. Target binding kinetics and metabolic stability data are included. These potent mutant EGFR inhibitors may serve as a basis for the development of structurally novel EGFR probes, tools, or candidates.
Patient Education in a 14-month Randomised Trial Fails to Improve Adherence in Ulcerative Colitis: Influence of Demographic and Clinical Parameters on Non-adherence
2017-05-08

Recent observational studies document that non-adherence to mesalamine therapy during remission is frequent. We aimed to investigate patient impact of patient education using objective assessments of adherence. A 14-month randomised, prospective clinical trial of adherence to mesalamine was conducted in 248 patients with ulcerative colitis [UC], Colitis Activity Index [CAI] ≤ 9, receiving standard care [n = 122] versus a standardised patient education programme [n = 126]. Primary endpoint was adherence at all visits (5-aminosalicylic acid [5-ASA] urine levels). Secondary endpoints included quality of life (inflammatory bowel disease questionnaise [IBDQ]), disease activity, partial adherence, and self-assessment of adherence. Patient allocation was well balanced. Baseline non-adherence was high in quiescent/mildly active UC [52.4%] without difference between the groups (52.4% of patients in the education group versus 52.5% in the standard care group [p = 0.99]). No difference between the intervention group and standard care was seen in IBDQ, partial adherence, self-assessment of adherence, or therapy satisfaction at all visits. We suggest a model in which individual risks for non-adherence are driven by patients with young age, short disease duration, and low education levels. Non-adherence is frequent in a population with quiescent/mildly active UC. Although more than 25% of the population was not in remission at the various time points, no relationship between disease activity and adherence was seen over the 14-month observation period. Physicians should maximise their efforts to motivate high-risk patients for adherence. Future trials should use objective exposure assessments to examine the impact of continuous education and consultations on the background of individual risks to develop non-adherence.