julilili42/papers huggingface dataset:
NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy
2015-09-04

ABSTRACT<b>Background.</b> To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only.<b>Materials and methods.</b> For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCP<sub>IMXT-IMPT</sub>) as well as between IMXT and the mixed modality treatment (∆NTCP<sub>IMXT-Mix</sub>) were calculated.<b>Results.</b> Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCP<sub>IMXT-Mix</sub> values were a factor 2–10 smaller than ∆NTCP<sub>IMXT-IMPT</sub>. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost.<b>Conclusions.</b> The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.
The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2
2015-09-04

The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte-lineage cells are particularly sensitive to stress resulting in cell death in white matter after hypoxic or ischemic insults of premature infants and destruction of OPC in some types of Multiple Sclerosis lesions. Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to stress. In the cytosol, OMI/HtrA2 initiates apoptosis by proteolytic degradation of anti-apoptotic factors. OPC in which NG2 has been downregulated by siRNA, or OPC from the NG2-knockout mouse show an increased sensitivity to oxidative stress evidenced by increased cell death. The proapoptotic protease activity of OMI/HtrA2 in the cytosol can be reduced by the interaction with NG2. Human glioma expressing high levels of NG2 are less sensitive to oxidative stress than those with lower NG2 expression and reducing NG2 expression by siRNA increases cell death in response to oxidative stress. Binding of NG2 to OMI/HtrA2 may thus help protect cells against oxidative stress-induced cell death. This interaction is likely to contribute to the high chemo- and radioresistance of glioma.
Comparison of Positron Emission Tomography Quantification Using Magnetic Resonance– and Computed Tomography–Based Attenuation Correction in Physiological Tissues and Lesions
2015-09-05

Results obtained using different PET tracers show that MR-based AC is accurate in most tissue types, with SUV deviations generally of less than 10%. In bone, however, underestimations can be pronounced, potentially leading to inaccurate SUV quantifications. In addition, SUV overestimations were found for some lesions close to lung borders. This has to be taken into account when comparing PET/CT- and PET/MR-derived SUVs.
Heritability of metoprolol and torsemide pharmacokinetics
2015-09-07

Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms in CYP2D6 , CYP2C9 , and OATP1B1 has been extensively studied. However, it is still unknown how much of the variation in pharmacokinetics of these two clinically important drugs in total is due to genetic factors. Metoprolol and torsemide were intravenously administered to 44 monozygotic and 14 dizygotic twin pairs. Metoprolol area under the curve (AUC) varied 4.7‐fold and torsemide AUC 3.5‐fold. A very high fraction of AUC variations, 91% of metoprolol and 86% of torsemide, were found to be due to additive genetic effects. However, known genetic variants of CYP2D6, ‐2C9, and OATP1B1 explained only 39%, 2%, and 39% of that variation, respectively. Comparable results for genetically explained variation in pharmacokinetics and pharmacodynamics have been found for other substrates of these enzymes earlier. These findings indicate that a substantial fraction of the heritable variability in the pharmacokinetics of metoprolol and torsemide remains to be elucidated.
Efficiency of stepwise magnetic-chemical site assessment for fly ash derived heavy metal pollution
2015-09-07

Previous works revealed a close relationship between magnetic susceptibility (MS) and heavy metal (HM) contents originating from industrial sources. However, despite general statements on the usefulness of magnetic mapping, the benefit of this procedure for geochemistry was not quantified yet. We present a study on fly ash pollution in soil around a coal-burning power plant complex and simulate a stepwise approach of magnetic pre-screening and subsequent targeted sampling for chemical analysis. The aim of this study is not to discuss correlations between MS and HM, but to show that a combined stepwise magnetic-chemical approach is the most efficient way for outlining HM contamination. In order to provide quantitative evidence, we explored map similarities of spatial HM distributions based on magnetochemical data and chemical data only. We determined 3-D triangular planes defined by categorized HM values at the sampling coordinates and calculated the average dihedral angle of the normal vectors as a similarity result. The study shows that the 'Targeted' HM map (selection of 30 sites based magnetic pre-screening) has a higher similarity with the 'True' Pollution HM map (85 sites) than HM maps resulting from site selections (30 sites) without using magnetic pre-screening information.
Comparison of user‐friendliness and treatment cost of Loceryl® vs. Ciclopoli® – a patient's perspective
2015-09-07

Summary Topical monotherapy is a valid therapeutic approach in onychomycosis. Due to its lengthy course and its non‐reimbursed product status, cost and compliance are important issues and non‐pharmacological properties such as over‐the‐counter price and ease of use should be considered when deciding which product to recommend. We investigated surrogate parameters for patient‐friendliness and treatment cost in Germany in a questionnaire‐based prospective, comparative, intra‐individual, open‐label trial of the two common topical antifungal nail lacquers Loceryl ® (amorolfine 5%) and Ciclopoli ® (ciclopirox 8%) in eight patients with clinically diagnosed onychomycosis. The 2.5 ml bottle of Loceryl ® covered a treatment period of 308 days, resulting in treatment costs of €0.10 per day in comparison to the 3.3 ml bottle of Ciclopoli ® , covering 127 days at €0.21 per day, given once‐daily application for Ciclopoli ® and once‐weekly application for Loceryl ® in accordance with regulatory approval. Six out of eight patients favoured the Loceryl ® treatment regimen. Furthermore, four out of eight patients found Loceryl ® easier to apply, whereas three preferred Ciclopoli ® . In total, seven out of eight stated a clear preference for Loceryl ® over Ciclopoli ® . Loceryl ® therapy is less expensive and less time‐consuming. The therapeutic period that can be covered is longer and more patients stated a clear preference for Loceryl ® in comparison to Ciclopoli ® . The differences are statistically significant, underlining probable clinical relevance.
Determination of the absolute configuration of a chiral epoxide using foil induced Coulomb explosion imaging
2015-09-07

We have applied the method of foil-induced Coulomb Explosion Imaging (FCEI) to determine the handedness of a homochiral sample of the compound trans-2,3-dideuterooxirane C2OH2D2. We determined the compound to be of the (R, R)-econfiguration with a statistical significance of 5σ. As the molecular sample was chemically linked to the stereochemical reference standard glyceraldehyde, our assignment constitutes an independent verification of the absolute handedness of all compounds linked to this reference substance.
Identification of Four Mouse Diabetes Candidate Genes Altering β-Cell Proliferation
2015-09-08

Beta-cell apoptosis and failure to induce beta-cell regeneration are hallmarks of type 2-like diabetes in mouse models. Here we show that islets from obese, diabetes-susceptible New Zealand Obese (NZO) mice, in contrast to diabetes-resistant C57BL/6J (B6)-ob/ob mice, do not proliferate in response to an in-vivo glucose challenge but lose their beta-cells. Genome-wide RNAseq based transcriptomics indicated an induction of 22 cell cycle-associated genes in B6-ob/ob islets that did not respond in NZO islets. Of all genes differentially expressed in islets of the two strains, seven mapped to the diabesity QTL Nob3, and were hypomorphic in either NZO (Lefty1, Apoa2, Pcp4l1, Mndal, Slamf7, Pydc3) or B6 (Ifi202b). Adenoviral overexpression of Lefty1, Apoa2, and Pcp4l1 in primary islet cells increased proliferation, whereas overexpression of Ifi202b suppressed it. We conclude that the identified genes in synergy with obesity and insulin resistance participate in adaptive islet hyperplasia and prevention from severe diabetes in B6-ob/ob mice.
Apparent diffusion coefficient-dependent voxelwise computed diffusion-weighted imaging: An approach for improving SNR and reducingT2shine-through effects
2015-09-08

vcDWI is a promising approach for the reduction of T2 shine-through effects and improvement of SNR and CNR in DWI. The clinical significance of these improvements, especially regarding lesion detection, needs to be evaluated in larger prospective clinical studies.
The Impact of Advice Seekers’ Need Salience and Doctors’ Communication Style on Attitude and Decision Making: A Web-Based Mammography Consultation Role Play
2015-09-08

The findings underline the importance of communicating in a need-oriented style with patients and advice seekers who are aware of their personal needs. Ignoring the needs of those people appears to be particularly problematic. So physicians' sensitivity for advice seekers' currently relevant needs is essential.
Reaction of Iron‐ and Tungsten Carbonyls with a Zwitterionic Fulvalene
2015-09-08

Abstract The highly dipolar fulvalene 1 reacts with pentacarbonyl iron(0) and hexacarbonyl tungsten(0) complexes under irradiation with UV light. The cyclopentadienyl complexes 2 and 3 formed are analysed by means of NMR and IR spectroscopy as well as X‐ray analysis. They are the first zwitterionic carbonyl complexes of fulvenes or fulvalenes. In the case of iron, the dinuclear complex 2 consisting of a dicarbonyliron(+I)‐tetracarbonylferrat(–I) moiety is formed, whereas in the case of tungsten, the mononuclear tricarbonyl tungsten(0) complex 3 is obtained.
Anatomical Organization and Spatiotemporal Firing Patterns of Layer 3 Neurons in the Rat Medial Entorhinal Cortex
2015-09-09

Layer 3 of the medial entorhinal cortex is a major gateway from the neocortex to the hippocampus. Here we addressed structure-function relationships in medial entorhinal cortex layer 3 by combining anatomical analysis with juxtacellular identification of single neurons in freely behaving rats. Anatomically, layer 3 appears as a relatively homogeneous cell sheet. Dual-retrograde neuronal tracing experiments indicate a large overlap between layer 3 pyramidal populations, which project to ipsilateral hippocampus, and the contralateral medial entorhinal cortex. These cells were intermingled within layer 3, and had similar morphological and intrinsic electrophysiological properties. Dendritic trees of layer 3 neurons largely avoided the calbindin-positive patches in layer 2. Identification of layer 3 neurons during spatial exploration (n = 17) and extracellular recordings (n = 52) pointed to homogeneous spatial discharge patterns. Layer 3 neurons showed only weak spiking theta rhythmicity and sparse head-direction selectivity. A majority of cells (50 of 69) showed no significant spatial modulation. All of the ∼28% of neurons that carried significant amounts of spatial information (19 of 69) discharged in irregular spatial patterns. Thus, layer 3 spatiotemporal firing properties are remarkably different from those of layer 2, where theta rhythmicity is prominent and spatially modulated cells often discharge in grid or border patterns. Significance statement: Neurons within the superficial layers of the medial entorhinal cortex (MEC) often discharge in border, head-direction, and theta-modulated grid patterns. It is still largely unknown how defined discharge patterns relate to cellular diversity in the superficial layers of the MEC. In the present study, we addressed this issue by combining anatomical analysis with juxtacellular identification of single layer 3 neurons in freely behaving rats. We provide evidence that the anatomical organization and spatiotemporal firing properties of layer 3 neurons are remarkably different from those in layer 2. Specifically, most layer 3 neurons discharged in spatially irregular firing patterns, with weak theta-modulation and head-directional selectivity. This work thus poses constraints on the spatiotemporal patterns reaching downstream targets, like the hippocampus.
Distress Calls of a Fast-Flying Bat (Molossus molossus) Provoke Inspection Flights but Not Cooperative Mobbing
2015-09-09

Many birds and mammals produce distress calls when captured. Bats often approach speakers playing conspecific distress calls, which has led to the hypothesis that bat distress calls promote cooperative mobbing. An alternative explanation is that approaching bats are selfishly assessing predation risk. Previous playback studies on bat distress calls involved species with highly maneuverable flight, capable of making close passes and tight circles around speakers, which can look like mobbing. We broadcast distress calls recorded from the velvety free-tailed bat, Molossus molossus, a fast-flying aerial-hawker with relatively poor maneuverability. Based on their flight behavior, we predicted that, in response to distress call playbacks, M. molossus would make individual passing inspection flights but would not approach in groups or approach within a meter of the distress call source. By recording responses via ultrasonic recording and infrared video, we found that M. molossus, and to a lesser extent Saccopteryx bilineata, made more flight passes during distress call playbacks compared to noise. However, only the more maneuverable S. bilineata made close approaches to the speaker, and we found no evidence of mobbing in groups. Instead, our findings are consistent with the hypothesis that single bats approached distress calls simply to investigate the situation. These results suggest that approaches by bats to distress calls should not suffice as clear evidence for mobbing.
Bidirectional Echolocation in the Bat Barbastella barbastellus: Different Signals of Low Source Level Are Emitted Upward through the Nose and Downward through the Mouth
2015-09-09

The Barbastelle bat (Barbastella barbastellus) preys almost exclusively on tympanate moths. While foraging, this species alternates between two different signal types. We investigated whether these signals differ in emission direction or source level (SL) as assumed from earlier single microphone recordings. We used two different settings of a 16-microphone array to determine SL and sonar beam direction at various locations in the field. Both types of search signals had low SLs (81 and 82 dB SPL rms re 1 m) as compared to other aerial-hawking bats. These two signal types were emitted in different directions; type 1 signals were directed downward and type 2 signals upward. The angle between beam directions was approximately 70°. Barbastelle bats are able to emit signals through both the mouth and the nostrils. As mouth and nostrils are roughly perpendicular to each other, we conclude that type 1 signals are emitted through the mouth while type 2 signals and approach signals are emitted through the nose. We hypothesize that the "stealth" echolocation system of B. barbastellus is bifunctional. The more upward directed nose signals may be mainly used for search and localization of prey. Their low SL prevents an early detection by eared moths but comes at the expense of a strongly reduced detection range for the environment below the bat. The more downward directed mouth signals may have evolved to compensate for this disadvantage and may be mainly used for spatial orientation. We suggest that the possibly bifunctional echolocation system of B. barbastellus has been adapted to the selective foraging of eared moths and is an excellent example of a sophisticated sensory arms race between predator and prey.
Enantioselective Synthesis of D‐α‐(Uracil‐5‐yl)glycine Derivatives and Their Racemization‐Free Incorporation into a Model Peptide
2015-09-09

Abstract An efficient asymmetric synthesis of D ‐α‐(uracil‐5‐yl)glycine derivatives using an enzymatic dynamic kinetic resolution of D , L ‐hydantoin intermediates with an immobilized D ‐hydantoinase ( D ‐Hyd‐1) is described. In addition, mild conditions for a racemization‐free solid‐phase peptide synthesis (SPPS) using the Fmoc strategy have been found.
Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type
2015-09-10

Abstract Small cell carcinoma of the ovary, hypercalcaemic type ( SCCOHT ) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 ( BRG1 ), one of two mutually exclusive ATPases of the SWI / SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT , we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours. Among ovarian tumours, it was only absent in clear cell carcinoma (15 of 360, 4%). In the uterus, it was absent in endometrial stromal sarcomas (4 of 52, 8%) and high‐grade endometrioid carcinomas (2 of 338, 1%). Recent studies have shown that SMARCA2 ( BRM ), the other mutually exclusive ATPase of the SWI / SNF complex, is necessary for survival of tumour cells lacking SMARCA4 . Therefore, we examined SMARCA2 expression and discovered that all SMARCA4 ‐negative SCCOHTs also lacked SMARCA2 protein by IHC , including the SCCOHT cell lines BIN67 and SCCOHT1 . Among ovarian tumours, the SMARCA4 / SMARCA2 dual loss phenotype appears completely specific for SCCOHT . SMARCA2 loss was not due to mutation but rather from an absence of mRNA expression, which was restored by treatment with the histone deacetylase inhibitor trichostatin A. Re‐expression of SMARCA4 or SMARCA2 inhibited the growth of BIN67 and SCCOHT1 cell lines. Our results indicate that SMARCA4 loss, either alone or with SMARCA2 , is highly sensitive and specific for SCCOHT and that restoration of either SWI / SNF ATPase can inhibit the growth of SCCOHT cell lines. © 2015 The Authors. The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Hadron fragmentation inside jets in hadronic collisions
2015-09-10

We present an analytical next-to-leading-order QCD calculation of the partonic cross sections for the process pp -&gt; (jeth)X, for which a specific hadron is observed inside a fully reconstructed jet. In order to obtain the analytical results, we assume the jet to be relatively narrow. We show that the results can be cast into a simple and systematic form based on suitable universal jet functions for the process. We confirm the validity of our calculation by comparing to previous results in the literature for which the next-to-leading-order cross section was treated entirely numerically by Monte Carlo integration techniques. We present phenomenological results for experiments at the LHC and at RHIC. These suggest that pp -&gt; (jeth)X should enable very sensitive probes of fragmentation functions, especially of the one for gluons.
A functional approach to movement analysis and error identification in sports and physical education
2015-09-10

In a hypothesis-and-theory paper, a functional approach to movement analysis in sports is introduced. In this approach, contrary to classical concepts, it is not anymore the "ideal" movement of elite athletes that is taken as a template for the movements produced by learners. Instead, movements are understood as the means to solve given tasks that in turn, are defined by to-be-achieved task goals. A functional analysis comprises the steps of (1) recognizing constraints that define the functional structure, (2) identifying sub-actions that subserve the achievement of structure-dependent goals, (3) explicating modalities as specifics of the movement execution, and (4) assigning functions to actions, sub-actions and modalities. Regarding motor-control theory, a functional approach can be linked to a dynamical-system framework of behavioral shaping, to cognitive models of modular effect-related motor control as well as to explicit concepts of goal setting and goal achievement. Finally, it is shown that a functional approach is of particular help for sports practice in the context of structuring part practice, recognizing functionally equivalent task solutions, finding innovative technique alternatives, distinguishing errors from style, and identifying root causes of movement errors.