julilili42/papers huggingface dataset:
Pupil response as an indicator of hazard perception during simulator driving
2017-11-06

We investigate the pupil response to hazard perception during driving simulation. Complementary to gaze movement and physiological stress indicators, pupil size changes can provide valuable information on traffic hazard perception with a relatively low temporal delay. We tackle the challenge of identifying those pupil dilation events associated with hazardous events from a noisy signal by a combination of wavelet transformation and machine learning. Therefore, we use features of the wavelet components as training data of a support vector machine. We further demonstrate how to utilize the method for the analysis of actual hazard perception and how it may differ from the behavioral driving response.
Motor expertise facilitates the accuracy of state extrapolation in perception
2017-11-06

Predicting the behavior of objects in the environment is an important requirement to overcome latencies in the sensorimotor system and realize precise actions in rapid situations. Internal forward models that were acquired during motor training might not only be used for efficiently controlling fast motor behavior but also to facilitate extrapolation performance in purely perceptual tasks. In this study, we investigated whether preceding virtual cart-pole balancing training facilitates the ability to extrapolate the virtual pole motion. Specifically, subjects had to report the expected pole orientation after an occlusion of the pole of 900ms duration. We compared a group of 10 subjects, proficient in performing the virtual cart-pole balancing task, to 10 naïve subjects without motor experience in cart-pole balancing task. Our results demonstrate that preceding motor training increases the accuracy of pole movement extrapolation, although extrapolation is not trained explicitly. Additionally, we modelled subjects' behaviors and show that the difference in extrapolation performance can be explained by individual differences in the accuracy of internal forward models. When subjects are provided with feedback about the true orientation of the pole after the occlusion in a second phase of the experiment, both groups improve rapidly. The results indicate that the perceptual capability to extrapolate the state of the cart-pole system accurately is implicitly trained during motor learning. We discuss these results in the context of shared representations and action-perception transfer.
Geochemical and Petrographic Analysis of Late Bronze Age Cypriot Ceramics (White Slip I and II and Monochrome) from Tell Atchana/Alalakh (Hatay) in the Amuq Valley
2017-11-06

White Slip ware, both White Slip I and II, and Monochrome ware are Middle to Late Bronze Age Cypriot pottery types found across a large area of the Eastern Mediterranean region. A vast quantity of these wares has also been uncovered in Tell Atchana/ancient Alalakh in Hatay in southern Anatolia. We analysed a total of 56 White Slip ( n = 36) and Monochrome potsherds ( n = 20) from Tell Atchana using XRF, ICP–MS and petrographic thin‐section methods. The main aim of the study was to explore the compositional characteristics of the wares and to determine whether they are local imitations of the Cypriot White Slip and Monochrome wares or represent Cypriot exports to this region. The analytical results proved that White Slip I and II were produced from raw clay of mafic and ultramafic source rocks exposed in the Troodos Massif, available in the Limassol area of southern Cyprus and traded to Tell Atchana. Examples of Monochrome ware excavated in Tell Atchana were also imported to the region, most probably from east/north‐east Cyprus. These results demonstrate a close trading connection between Tell Atchana/ Alalakh and southern Cyprus during the Middle to Late Bronze Age.
A Rare Differential Diagnosis of an Adrenal Mass: A Case Report
2017-11-06

Ten years after his last treatment for diffuse large B-cell lymphoma, a seemingly healthy, 64-year-old man presented for his lymphoma-related follow-up. Ultrasound revealed an impressive tumor in the right adrenal gland. Due to recurrent cancer therapies in the past, this seemed highly suspicious of a second malignancy, such as primary adrenal carcinoma. Surprisingly, histology disclosed a very different but rare cause for this pseudotumorous lesion.
The CERAD Neuropsychological Assessment Battery Is Sensitive to Alcohol-Related Cognitive Deficiencies in Elderly Patients: A Retrospective Matched Case-Control Study
2017-11-06

Abstract Objectives: Adverse effects of heavy drinking on cognition have frequently been reported. In the present study, we systematically examined for the first time whether clinical neuropsychological assessments may be sensitive to alcohol abuse in elderly patients with suspected minor neurocognitive disorder. Methods: A total of 144 elderly with and without alcohol abuse (each group n =72; mean age 66.7 years) were selected from a patient pool of n =738 by applying propensity score matching (a statistical method allowing to match participants in experimental and control group by balancing various covariates to reduce selection bias). Accordingly, study groups were almost perfectly matched regarding age, education, gender, and Mini Mental State Examination score. Neuropsychological performance was measured using the CERAD (Consortium to Establish a Registry for Alzheimer’s Disease). Classification analyses (i.e., decision tree and boosted trees models) were conducted to examine whether CERAD variables or total score contributed to group classification. Results: Decision tree models disclosed that groups could be reliably classified based on the CERAD variables “Word List Discriminability” (tapping verbal recognition memory, 64% classification accuracy) and “Trail Making Test A” (measuring visuo-motor speed, 59% classification accuracy). Boosted tree analyses further indicated the sensitivity of “Word List Recall” (measuring free verbal recall) for discriminating elderly with versus without a history of alcohol abuse. Conclusions: This indicates that specific CERAD variables seem to be sensitive to alcohol-related cognitive dysfunctions in elderly patients with suspected minor neurocognitive disorder. ( JINS , 2018, 24 , 360–371)
Secondary Breast Lymphoma: A Case Report
2017-11-06

&lt;p&gt;Breast lymphomas are a rare sighting and image fi ndings are non&lt;/p&gt; &lt;p&gt;-pathognomonic often mimicing&lt;/p&gt; &lt;p&gt;different forms of invasive breast cancer. Nevertheless, multim&lt;/p&gt; &lt;p&gt;odal imaging and subsequent histopathology&lt;/p&gt; &lt;p&gt;are crucial for diagnosis and treatment. To draw attention to t&lt;/p&gt; &lt;p&gt;his very rare entity, we present a case of&lt;/p&gt; &lt;p&gt;a 74 year old female patient with a tumorous mass in the left m&lt;/p&gt; &lt;p&gt;axillary sinus. The subsequent whole-&lt;/p&gt; &lt;p&gt;body staging CT revealed an additional multicentric lesion of t&lt;/p&gt; &lt;p&gt;he right breast suggesting breast cancer.&lt;/p&gt; &lt;p&gt;Histopathology of both lesions resulted in the diagnosis of a d&lt;/p&gt; &lt;p&gt;iffuse large B cell lymphoma (DLBCL).&lt;/p&gt;
Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study
2017-11-07

BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p &lt; 0.0001), but this effect was not apparent at a later FFTP. CONCLUSIONS: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.
A New Strain Collection for Improved Expression of Outer Membrane Proteins
2017-11-07

Almost all integral membrane proteins found in the outer membranes of Gram-negative bacteria belong to the transmembrane β-barrel family. These proteins are not only important for nutrient uptake and homeostasis, but are also involved in such processes as adhesion, protein secretion, biofilm formation, and virulence. As surface exposed molecules, outer membrane β-barrel proteins are also potential drug and vaccine targets. High production levels of heterologously expressed proteins are desirable for biochemical and especially structural studies, but over-expression and subsequent purification of membrane proteins, including outer membrane proteins, can be challenging. Here, we present a set of deletion mutants derived from <i>E. coli</i> BL21 Gold (DE3) designed for the over-expression of recombinant outer membrane proteins. These strains harbor deletions of four genes encoding abundant β-barrel proteins in the outer membrane (OmpA, OmpC, OmpF, and LamB), both single and in all combinations of double, triple, and quadruple knock-outs. The sequences encoding these outer membrane proteins were deleted completely, leaving only a minimal scar sequence, thus preventing the possibility of genetic reversion. Expression tests in the quadruple mutant strain with four test proteins, including a small outer membrane β-barrel protein and variants thereof as well as two virulence-related autotransporters, showed significantly improved expression and better quality of the produced proteins over the parent strain. Differences in growth behavior and aggregation in the presence of high salt were observed, but these phenomena did not negatively influence the expression in the quadruple mutant strain when handled as we recommend. The strains produced in this study can be used for outer membrane protein production and purification, but are also uniquely useful for labeling experiments for biophysical measurements in the native membrane environment.
Cancer vaccines and immunotherapeutic approaches in hepatobiliary and pancreatic cancers
2017-11-07

Hepatobiliary and pancreatic cancers along with other gastrointestinal malignancies remain the leading cause of cancer-related deaths worldwide. Strategies developed in the recent years on immunotherapy and cancer vaccines in the setting of primary liver cancer as well as in pancreatic cancer are the scope of this review. Significance of orthotopic and autochthonous animal models which mimic and/or closely reflect human malignancies allowing for a prompt and trustworthy analysis of new therapeutics is underlined. Combinational approaches that on one hand, specifically target a defined cancer-driving pathway, and on the other hand, restore the functions of immune cells, which effector functions are often suppressed by a tumor milieu, are shown to have the strongest perspectives and future directions. Among combinational immunotherapeutic approaches a personalized- and individual cancer case-based therapy is of special importance.
Intramolecular Diels–Alder Reactions of Tethered Enoate Substituted Furans Induced by Dialkylaluminum Chloride
2017-11-07

Gold(I)-catalyzed cycloisomerization of enynols 11 and 17, obtained by Sonogashira coupling, led to the tethered enoate-substituted furans 14 and 19. While attempts at thermal and several Lewis acid induced intramolecular Diels-Alder reactions remained fruitless, dialkylaluminum chloride led to the formation of hexahydroindene and octahydronaphthalene derivatives 20-23. Their formation can be explained by Lewis acid induced opening of the epoxy bridge with transfer of one alkyl group to the intermediate cycloadduct.
The Impact of Topic Characteristics and Threat on Willingness to Engage with Wikipedia Articles: Insights from Laboratory Experiments
2017-11-07

A growing body of research aims to identify the factors that motivate people to make contributions in Wikipedia. We conducted two laboratory experiments to investigate the connections between topic characteristics, perception of threat, and willingness to engage with Wikipedia articles. In Study 1 (<i>N</i> = 83), we examined how topic familiarity, topic controversiality, and mortality salience influenced participants' willingness to engage with Wikipedia articles. We presented the introduction parts of 20 Wikipedia articles and asked participants to rate each article with respect to familiarity and controversiality. In addition, we experimentally manipulated participants' level of mortality salience in terms of the amount of threat they experienced when reading the article. Participants also indicated their willingness to engage with a particular article. The results revealed that familiar and controversial topics increased the willingness to engage with Wikipedia articles. Although mortality salience increased accessibility of death-related thoughts, it did not result in any changes in people's willingness to work with the articles. The aim of Study 2 (<i>N</i> = 90) was to replicate the effects of topic characteristics by following a similar procedure. We additionally manipulated uncertainty salience by assigning participants to three experimental conditions: uncertainty salience, certainty salience, and non-salience. As expected, familiar and controversial topics were of high interest in terms of willingness to contribute. However, the manipulation of uncertainty salience did not yield any significant results despite the emergence of negative emotional states. In sum, we demonstrated that topic characteristics were factors that substantially influenced people's willingness to engage with Wikipedia articles whereas perceived threat was not.
Addressing the reliability fallacy: Similar group effects may arise from unreliable individual effects
2017-11-07

Abstract To cast valid predictions of future behavior or diagnose disorders, the reliable measurement of a “biomarker” such as the brain activation to prospective reward is a prerequisite. Surprisingly, only a small fraction of functional magnetic resonance imaging (fMRI) studies report or cite the reliability of brain activation maps involved in group analyses. Here, using simulations and exemplary longitudinal data of 126 healthy adolescents performing an intertemporal choice task, we demonstrate that reproducing a group activation map over time is not a sufficient indication of reliable measurements at the individual level. Instead, selecting regions based on significant main effects at the group level may yield estimates that fail to reliably capture individual variance in the subjective evaluation of an offer. Collectively, our results call for more attention on the reliability of supposed biomarkers at the level of the individual. Thus, caution is warranted in employing brain activation patterns prematurely for clinical applications such as diagnosis or tailored interventions before their reliability has been conclusively established by large-scale studies. To facilitate assessing and reporting of the reliability of fMRI contrasts in future studies, we provide a toolbox that incorporates common measures of global and local reliability.
The impact of high-end ultrasound in the management of a patient with neuroendocrine tumor of the ileum
2017-11-07

Abstract Diagnostic imaging of jejuno-ileal neuroendocrine tumors (NETs) has been described as challenging. Follow-up requires the detection of metastatic spread as well as screening for local recurrence. Multimodal imaging concepts must often be applied. We report the case of a 45-year-old man with a history of ileal NET. At 2 points in follow-up of our patient, information provided by high-end ultrasound changed prognosis and treatment considerably: when positron emission tomography/computed tomography newly detected suspected hepatic metastases, contrast-enhanced ultrasound correctly identified the lesions as intrahepatic vascular shunts. Moreover, profound B-mode ultrasound solely detected ileal recurrence, leading to early removal of the tumor.
Bruton’s Tyrosine Kinase: An Emerging Key Player in Innate Immunity
2017-11-08

Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thorough basic understanding of the human innate immune system but also as a target to therapeutically modulate innate immunity. We here review the latest developments on the role of BTK in mononuclear innate immune cells in mouse versus man, with specific emphasis on the sensing of infectious agents and the induction of inflammation. Therapeutic implications for modulating innate immunity and critical open questions are also discussed.
Superior Retinal Gene Transfer and Biodistribution Profile of Subretinal Versus Intravitreal Delivery of AAV8 in Nonhuman Primates
2017-11-08

Purpose: To investigate shedding and biodistribution characteristics of recombinant adeno-associated virus serotype 8 (rAAV8) after single-dose subretinal or intravitreal injection in nonhuman primates (NHP, Macaca fascicularis) as a surrogate for environmental hazard and patient safety. Methods: In a study for regulatory submission, 22 NHP were divided into four cohorts receiving either single subretinal injections of vehicle or clinical grade rAAV8 (1 × 1011 or 1 × 1012 vector genomes [vg]) versus single intravitreal application of 1 × 1012 vg. Viral shedding and biodistribution were monitored in biofluids for up to 91 days, followed by necropsy and tissue harvesting of all major organs, the visual pathway, and lymphatic tissue. Quantification of vector genomes was done by quantitative (q)PCR. Results: Shedding occurred in a dose-dependent manner in all biofluids and persisted for a maximum of 7 days. Intravitreal delivery led to increased and persistent (up to 13 weeks) distribution of vector genomes in blood and draining lymphatic tissue, increased off-target deposition, and inefficient gene transfer to the retina. No vector targeting of the germ line was observed in any cohort. Conclusions: These data illustrate that subretinal application of rAAV8 leads to a more favorable biodistribution profile compared to intravitreal injections. Extraocular biodistribution is limited after subretinal delivery, while intravitreal injection leads to both greater and more persistent systemic exposure, evident in blood and lymphatic tissues. With the knowledge on the dynamics of shedding in a setting mimicking clinical application, guidelines can be developed to refine clinical trial protocols to reduce the risk for trial subjects and their environment.
Immunotherapy for kidney cancer
2017-11-08

The current treatment landscape in mRCC is shifting towards immunooncology agents, which already gained ground in the clinic as ICI monotherapy (nivolumab) or is likely to do in the near future as ICI combination (nivolumab and ipilimumab). The future will hold promise of new combinations with TKIs and ICI or other immunooncology agents like vaccines and metabolic immune checkpoint inhibitors.
Sleep in Humans Stabilizes Pattern Separation Performance
2017-11-08

Replay of hippocampal neural representations during sleep is thought to promote systems consolidation of declarative memory. How this reprocessing of memory during sleep affects the hippocampal representation itself, is unclear. Here we tested hippocampal stimulus processing (i.e., pattern separation) before and after periods of sleep and wakefulness in humans (female and male participants). Pattern separation deteriorated across the wake period but remained stable across sleep ( p = 0.013) with this sleep–wake difference being most pronounced for stimuli with low similarity to targets ( p = 0.006). Stimuli with the highest similarity showed a reversed pattern with reduced pattern separation performance after sleep ( p = 0.038). Pattern separation performance was positively correlated with sleep spindle density, slow oscillation density, and theta power phase-locked to slow oscillations. Sleep, presumably by neural memory replay, shapes hippocampal representations and enhances computations of pattern separation to subsequent presentation of similar stimuli. SIGNIFICANCE STATEMENT The consolidation of hippocampus-dependent memories is causally related to reactivation during sleep of previously encoded representations. Here, we show that reactivation-based consolidation processes during sleep shape the hippocampal representation itself. We studied the effect of sleep and wakefulness on pattern separation (i.e., orthogonalization of similar representations) and completion performance (i.e., recall of a memory in light of noisy input) that are essential cognitive elements of encoding and retrieval of information by the hippocampus. Our results demonstrate that pattern separation was stabilized after sleep but diminished after wakefulness. We further showed that pattern separation was related to EEG oscillatory parameters of non-REM sleep serving as markers of sleep-dependent memory consolidation and hippocampal reactivation.