julilili42/papers huggingface dataset:
Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression
2018-12-20

We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM (<i>clinicaltrials.gov identifier: 01332968</i>), and investigated the effect on early disease progression of the two randomization arms: obinutuzumab-based <i>versus</i> rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post randomization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601) <i>versus</i> rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95%CI: 25.0-61.1%; cumulative incidence rate 10.1% <i>vs</i> 17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event [HR of time-varying progression status, 25.5 (95%CI: 16.2-40.3)]. Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression <i>versus</i> those without was 12.2 (95%CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progression did not seem to be influenced by treatment arm.
α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease
2018-12-20

Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.
Age estimation in foreign-accented speech by non-native speakers of English
2018-12-20

This project will investigate the effect language background has on non-native listeners’ age perception when listening to other non-native speakers speaking English. In the current study, speakers of Mandarin Chinese English, Arabic English and Korean English will listen to audio clips of native Mandarin Chinese, Arabic and Korean speakers speaking English. It seeks to fill the current gap in research on non-native language-users in age-estimation studies [1] [2] [3] [4] [5] [6].Our research questions are: 1) Is age perception accuracy affected by a listener’s language background and familiarity with the speaker’s native language? 2) Are speakers of some languages perceived as younger than speakers of other languages?Our hypotheses are broken down as follows:(a) Listeners will estimate more accurately and faster in their own language-accented English (‘own-accent’ advantage).(b) Listeners will estimate the ages of familiar language speakers more accurately and more quickly compared to unfamiliar language speakers (Koreans and Mandarin Chinese will estimate each other’s ages more accurately and quickly than the Arabic).(c) Mandarin Chinese and Korean speakers will be perceived as younger than the Arabic speakers.<b>References</b>[1] Braun, A., &amp; Cerrato, L. (1999). <i>Estimating speaker age across languages</i>. In Proceedings of ICPhS (Vol. 99, pp. 1369–1372). Retrieved from https://www.internationalphoneticassociation.org/icphs-proceedings/ICPhS1999/papers/p14_1369.pdf[2] Bürkle, D., &amp; Gnevsheva, K. (2017 in preparation). <i>Age estimation in foreign-accented speech</i>. In The International Conference on Language Variation in Europe (ICLaVE). Malaga, Spain.[3] Nagao, K., &amp; Kewley-Port, D. (2005). <i>The effect of language familiarity on age perception.</i> In International Research Conference on Aging and Speech Communication. Bloomington, Indiana.[4] Nagao, K. (2006). <i>Cross-language study of age perception</i> (Ph.D.). Indiana University, Bloomington, Indiana. Retrieved from http://search.proquest.com/docview/305335298[5] Rodrigues, P., &amp; Nagao, K. (2010). Effects of listener experience with foreign accent on perception of accentedness and speaker age. <i>The Journal of the Acoustical Society of America</i>, 127(3), 1956–1956. https://doi.org/10.1121/1.3384968[6] Weinberger, S. (2015). <i>Speech accent archive</i>. George Mason University. Retrieved from http://accent.gmu.edu
Photon-photon and photon-hadron processes in Pythia 8
2018-12-20

We present a new implementation of photoproduction processes in e+e- and ep collisions into Pythia 8 Monte-Carlo event-generator. In particular we discuss how the parton showers and multiparton interactions are generated with a resolved photon beam and what is the relative contribution from direct processes in different kinematical regions. As an application we show compa\\-risons to data for charged-particle production in e^+e^- and ep collisions at LEP and HERA. We consider also photoproduction of dijets comparing to data for ep collisions at HERA and discuss about possibility to further constrain nuclear PDFs with ultra-peripheral heavy-ion collisions at the LHC.
Using a machine learning approach to complement group level statistics in experimental psychology: A case study to reveal different levels of inhibition in a modified Flanker Task
2018-12-20

In this paper, we demonstrate how machine learning (ML) can be used to beneficially complement the traditional analysis of behavioral and physiological data to provide new insights into the structure of mental states, in this case, executive functions (EFs) with a focus on inhibitory control. We used a modified Flanker task with the aim to distinguish three levels of inhibitory control: no inhibition, readiness for inhibition and the actual execution of inhibitory control. A simultaneously presented n-back task was used to additionally induce demands on a second executive function. This design enabled us to investigate how the overlap of resources influences the distinction between three levels of inhibitory control. A support vector machine (SVM) based classification approach has been used on EEG data to predict the level of inhibitory control on single-subject and single-trial level. The SVM classification is a subject-specific and single-trial based approach which will be compared to standard group-level statistical approaches to reveal that both methodologies access different properties of the data. We show that considering both methods can give new insights into mental states which cannot be discovered when only using group-level statistics alone. Machine learning results indicate that three different levels of inhibitory control can be distinguished, while the group-average analysis does not give rise to this assumption. In addition, we highlight one other important benefit of the ML approach. We are able to define specific properties of the executive function inhibition by investigating the neural activation patterns that were used during the classification process.
Electric Spark Discharges in Water: Light Leptonic Magnetic Monopoles and Catalysis of Ordinary Beta Decays in an Extended Standard Model
2018-12-20

Abstract The topic of this article is “research of accidents induced by supersonic electric spark discharges in water”. Experiments referring to such accidents were published by Urutskoev et al. in 2000 and Urutskoev in 2004. According to Urutskoev these spark discharges should be accompanied by the emission of a new kind of particles, namely leptonic magnetic monopoles, predicted by Lochak in 1985. Later, Lochak considered these monopoles as excited neutrinos. Both Lochak and Urutskoev supposed that these particles can influence weak decays and nuclear transmutations and that by catalysis the monopole effect can be amplified, leading to macroscopic effects, i.e. accidents. Spark discharges in water are connected with CP-symmetry-breaking, forcing the introduction of an extended standard model described in previous papers. There also, a mechanism of the catalytic effect was discussed, which is further studied in this article. For the selected unstable nuclear element <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" display="inline"> <m:mmultiscripts> <m:mtext>Mn</m:mtext> <m:mprescripts /> <m:mn>25</m:mn> <m:mn>51</m:mn> </m:mmultiscripts> </m:math> , the effect is demonstrated and numerically evaluated. A simple non-relativistic nuclear state description is applied for these low-energy processes. The extension of these calculations to other unstable nuclei requires higher calculational effort and is not done in this paper. However, the extraordinarily strong catalytic power of the monopoles revealed by the numerical calculation of the above example suggests looking for macroscopic effects of monopoles as an explanation for accidents, for instance, the catastrophe of Chernobyl, which has been the origin of monopole research. A short review of the corresponding experimental observations connected with this accident is also given in this article.
Lost in Transmediation. Transmedial Adaption of Videogames and GDNA Theory
2018-12-20

Videogames and their transmedial adaptations share common persuasive messages. Their rhetoric is diverse, encompassing political as well as economic messages for the players. Yet, the possibilities to analyze the translation from videogames towards other media is so far limited. Without a systematic approach to address all circumstances behind videogame-rhetoric, the resulting insights for their transmedial satellites are difficult to compare. Therefore, this paper introduces the GDNA model. The Game Dynamic Narrative Analysis is crafted as a holistic approach. Based upon the notion of videogame as artificial orator (homunculus digitalis), it compares videogames analysis with DNA sequencing. Identifying rhetoric sequences within a game’s genome is marked by the interplay between those elements specific to games (like procedural rhetoric) and those transferred from other fields (like speech act analysis or visual rhetoric). Thereby, the GDNA model unifies narratological and ludological perspectives of game studies through incorporating both positions into every rhetorical analysis of games. As a result, it grants better understanding how game-specific elements are treated in their respective transmedial translation. In order to illustrate this, the Metal Gear Solid franchise was examined. Metal Gear Solid demonstrates different strategies for transmediation. With novelizations, comic books, digital graphic novels, audio drama and analog board games, the storyworld of Solid Snake and Big Boss became accessible for a wide audience. However, Hideo Kojima’s legacy contains a unique element that poses a problem to transfer from its videogame origin: immersion fractures. Those speech acts directly address the player and persuade her to change gameplay behavior. Examining scenes from the first two installments with the GDNA model illustrates that immersion fractures require specific adaptations to preserve their specific messages. Their respective novels, comics and digital graphic novels addressed this challenge quite differently. However, some messages got lost of in their transmediation.
Advisors want their advice to be used – but not too much: Comparing advisor expectations and advisee behavior in advice weighting
2018-12-20

&lt;p&gt;Much advice-taking research investigates whether advice weighting accords to normative principles. The present research complements this normative perspective with an interpersonal one, arguing that advisees should also attend to how much their advisors expect them to weight advice. Across three experiments, we find that advisors’ expectations of advice weighting are often congruent with advisees’ actual advice weighting, but moderators can cause expected and actual weighting to diverge (Experiments 1 &amp; 2). Increasing the difficulty of the task led advisors to want less weight on their advice, but advisees placed more weight on the advice for difficult items, thus overweighting advice compared to advisors’ expectations (Experiment 2). Importantly, both over- and underweighting of advice as compared to advisor expectations caused advisors to evaluate advisees more negatively, which resulted in reduced willingness to give advice again in the future (Experiment 3), indicating that advisors want their advice used, but not too much.&lt;/p&gt;
Advisors want their advice to be used – but not too much: An interpersonal perspective on advice taking
2018-12-20

Much advice taking research investigates whether advice weighting accords to normative principles for maximizing decision accuracy. The present research complements this normative perspective with an interpersonal one, arguing that judges should also pay attention to how much their advisors <em>want</em> them to weight advice. In four experiments, we found that advisors do not always want their advice to be adopted fully. Instead, they often give advice about which they are uncertain and therefore want their advice to be averaged with judges’ initial opinions or not used at all. Furthermore, advisors’ desired advice weighting is often congruent with the judges’ actual weighting, but moderators that affect advisor or judge confidence can cause desired and actual weighting to diverge (Experiments 1 and 2). When tasks were difficult, judges put more weight on the advice than advisors desired, because increasing the difficulty of the task led advisors to want their advice weighted less, whereas judges placed more weight on the advice. The reverse was true for easy tasks (Experiment 2). Importantly, both weighting more and less than advisors desired caused advisors to evaluate judges more negatively, which resulted in reduced willingness to give advice again in the future (Experiments 3 and 4), indicating that advisors want their advice used, but not too much.
Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer
2018-12-21

Cancer immunotherapy has been established as standard of care in different tumor entities. After the first reports on synergistic effects with radiotherapy and the induction of abscopal effects-tumor shrinkage outside the irradiated volume attributed to immunological effects of radiotherapy-several treatment combinations have been evaluated. Different immunotherapy strategies (e.g., immune checkpoint inhibition, vaccination, cytokine based therapies) have been combined with local tumor irradiation in preclinical models. Clinical trials are ongoing in different cancer entities with a broad range of immunotherapeutics and radiation schedules. SDF-1 (CXCL12)/CXCR4 signaling has been described to play a major role in tumor biology, especially in hypoxia adaptation, metastasis and migration. Local tumor irradiation is a known inducer of SDF-1 expression and release. CXCR4 also plays a major role in immunological processes. CXCR4 antagonists have been approved for the use of hematopoietic stem cell mobilization from the bone marrow. In addition, several groups reported an influence of the SDF-1/CXCR4 axis on intratumoral immune cell subsets and anti-tumor immune response. The aim of this review is to merge the knowledge on the role of SDF-1/CXCR4 in tumor biology, radiotherapy and immunotherapy of cancer and in combinatorial approaches.
Therapy Landscape in Patients with Metastatic HER2-Positive Breast Cancer: Data from the PRAEGNANT Real-World Breast Cancer Registry
2018-12-21

This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis
2018-12-21

Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies (IRD) and the most frequent cause of inherited blindness in children. The phenotypic overlap with other early-onset and severe IRDs as well as difficulties associated with the ophthalmic examination of infants can complicate the clinical diagnosis. To date, 25 genes have been implicated in the pathogenesis of LCA. The disorder is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. We report the mutation spectra and frequency of genes in 27 German index patients initially diagnosed with LCA. A total of 108 LCA- and other genes implicated in IRD were analysed using a cost-effective targeted next-generation sequencing procedure based on molecular inversion probes (MIPs). Sequencing and variant filtering led to the identification of putative pathogenic variants in 25 cases, thereby leading to a detection rate of 93%. The mutation spectrum comprises 34 different alleles, 17 of which are novel. In line with previous studies, the genetic results led to a revision of the initial clinical diagnosis in a substantial proportion of cases, demonstrating the importance of genetic testing in IRD. In addition, our detection rate of 93% shows that MIPs are a cost-efficient and sensitive tool for targeted next-generation sequencing in IRD.
Disruption of peroxisome proliferator–activated receptor γ coactivator (PGC)-1α reverts key features of the neoplastic phenotype of glioma cells
2018-12-21

The peroxisome proliferator-activated receptor γ coactivator (PGC)-1α is a master regulator of mitochondrial biogenesis and controls metabolism by coordinating transcriptional events. Here, we interrogated whether PGC-1α is involved in tumor growth and the metabolic flexibility of glioblastoma cells. PGC-1α was expressed in a subset of established glioma cell lines and primary glioblastoma cell cultures. Furthermore, a higher PGC-1α expression was associated with an adverse outcome in the TCGA glioblastoma dataset. Suppression of PGC-1α expression by shRNA in the PGC-1α-positive U343MG glioblastoma line suppressed mitochondrial gene expression, reduced mitochondrial membrane potential, and diminished oxygen as well as glucose consumption, and lactate production. Compatible with the known PGC-1α functions in reactive oxygen species (ROS) metabolism, glioblastoma cells deficient in PGC-1α displayed ROS accumulation, had reduced RNA levels of proteins involved in ROS detoxification, and were more susceptible to death induction by H<sub>2</sub>O<sub>2</sub> compared with control cells. PGC-1αsh cells also had impaired proliferation and migration rates <i>in vitro</i> and displayed less stem cell characteristics. Complementary effects were observed in PGC-1α-low LNT-229 cells engineered to overexpress PGC-1α. In an <i>in vivo</i> xenograft experiment, tumors formed by U343MG PGC-1αsh glioblastoma cells grew much slower than control tumors and were less invasive. Interestingly, the PGC-1α knockdown conferred protection against hypoxia-induced cell death, probably as a result of less active anabolic pathways, and this effect was associated with reduced epidermal growth factor expression and mammalian target of rapamycin signaling. In summary, PGC-1α modifies the neoplastic phenotype of glioblastoma cells toward more aggressive behavior and therefore makes PGC-1α a potential target for anti-glioblastoma therapies.
Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease
2018-12-21

<b>Background:</b> Blood levels of immune markers have been proposed to discriminate patients with Parkinson's disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified. <b>Objective:</b> To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients. <b>Methods:</b> Phenotypes of clinical PD from Tübingen, Germany (<i>n</i> = 145) and Toronto, Canada (<i>n</i> = 90) were defined regarding clinical subtype, disease onset, severity, and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical phenotypes after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of <i>in vivo</i> brain microglial activation. <b>Results:</b> Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET. <b>Conclusions:</b> Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity, and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage, and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes.