julilili42/papers huggingface dataset:
Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD
2018-12-18

Abstract Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3-ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P &amp;lt; .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606.
A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO)
2018-12-18

Abstract Purpose: To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer. Patients and Methods: ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. Results: We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31–75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10–35; cohort 1] and 37% [95% CI, 22–55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor–positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval &amp;lt;8 weeks; 47% ORR with interval &amp;gt;6 months). Conclusions: Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation.
Little Geodetic Evidence for Localized Indian Subduction in the Pamir‐Hindu Kush of Central Asia
2018-12-18

Abstract Geodetically derived velocities from Central Asia show that Northern Afghanistan, the Tajik Pamir, and northwestern Pakistan all move northward with comparable large velocities toward Eurasia. Steep velocity gradients, hence high strain rates, occur only across the Main Pamir Fault zone and with lesser magnitude between the northernmost Hindu Kush and the south and southeast margins of the Tajik Depression. Localized shortening is not apparent on any active India‐Hindu Kush crustal boundary; hence, crustal convergence between India and Eurasia in Central Asia is absorbed primarily on the northern and western margins of the Pamir. This concentrated strain on the Pamir margins is consistent with one, geometrically complex, interface between subducting Asian lithosphere and the Pamir. That interface might curve westward such that the Hindu Kush seismic zone is a continuation of the Pamir seismic zone, or alternatively, Hindu Kush earthquakes might occur in convectively unstable mantle lithosphere mechanically detached from surface faults.
Social Cognition in Down Syndrome: Face Tuning in Face-Like Non-Face Images
2018-12-18

Individuals with Down syndrome (DS) are widely believed to possess considerable socialization strengths. However, the findings on social cognition capabilities are controversial. In the present study, we investigated whether individuals with DS exhibit shortage in face tuning, one of the indispensable components of social cognition. For this purpose, we implemented a recently developed Face-n-Food paradigm with food-plate images composed of food ingredients such as fruits and vegetables. The key benefit of such face-like non-face images is that single elements do not facilitate face processing. In a spontaneous recognition task, 25 children with DS aged 9 to 18 years were presented with a set of Face-n-Food images bordering on the Giuseppe Arcimboldo style. The set of images was administered in a predetermined order from the least to most resembling a face. In DS individuals, thresholds for recognition of the Face-n-Food images as a face were drastically higher as compared not only with typically developing controls, but also with individuals with autistic spectrum disorders and Williams-Beuren syndrome. This outcome represents a significant step toward better conceptualization of the visual social world in DS and neurodevelopmental disorders in general.
U.S. Demand for European Soccer Telecasts: A Between-Country Test of the Uncertainty of Outcome Hypothesis
2018-12-18

Demand studies in sports relying on within-country settings are suggestive of cross-continental differences with regard to game uncertainty preferences. While North Americans seem to have a preference for tighter games, Europeans prefer games involving a favorite. Our study is the first to test this suggested pattern in a between-country setting with individual-level data. In contrast to the existing evidence from within-country settings, our demand models show that U.S. consumers do not value game uncertainty when watching European soccer. This finding suggests that, when examining the same sport, European and North American consumers’ preferences seem to be quite similar.
Vulnerability of frontal brain neurons for the toxicity of expanded ataxin-3
2018-12-18

Spinocerebellar ataxia type 3 (SCA3) is caused by the expansion of CAG repeats in the ATXN3 gene leading to an elongated polyglutamine tract in the ataxin-3 protein. Previously, we demonstrated that symptoms of SCA3 are reversible in the first conditional mouse model for SCA3 directing ataxin-3 predominantly to the hindbrain. Here, we report on the effects of transgenic ataxin-3 expression in forebrain regions. Employing the Tet-off CamKII-promoter mouse line and our previously published SCA3 responder line, we generated double transgenic mice (CamKII/MJD77), which develop a neurological phenotype characterized by impairment in rotarod performance, and deficits in learning new motor tasks as well as hyperactivity. Ataxin-3 and ubiquitin-positive inclusions are detected in brains of double transgenic CamKII/MJD77 mice. After turning off the expression of pathologically expanded ataxin-3, these inclusions disappear. However, the observed phenotype could not be reversed, very likely due to pronounced apoptotic cell death in the frontal brain. Our data demonstrate that cerebellar expression is not required to induce a neurological phenotype using expanded ATXN3 as well as the pronounced sensibility of forebrain neurons for toxic ataxin-3.
Does Regulation Trade Off Quality against Inequality? The Case of German Architects and Construction Engineers
2018-12-18

Abstract We exploit an exogenous price increase of 10 per cent for architectural services to answer the question how price regulation affects income inequality and service quality. Using individual‐level data from the German microcensus for the years 2006–2012, we find a significant reform effect of 8 per cent on personal net income for self‐employed architects and construction engineers. This group moved from the second lowest to the highest quintile of the net income distribution. This increase in inequality is associated with a deterioration of service quality. The reform reduced average scores of a peer ranking for architects by 18 per cent.
Using expatriates for adapting subsidiaries employment modes to different market economies: a comparative analysis of US subsidiaries in Germany, the UK and Switzerland
2018-12-18

Because the extent to which multinational companies (MNCs) benefit from foreign subsidiaries depends on how effectively MNCs manage their foreign subsidiaries' workforce, the international management literature has long focused on how MNCs transfer Human Resource Management (HRM) practices. However, the literature has only vaguely dealt with institutional differences between host and home countries, often simplifying these differences under the umbrella of institutional or cultural distance. This article investigates how MNCs use expatriates to adjust subsidiaries' employment modes to different market economies. We define employment modes as bundles of HRM and industrial relations (IR) practices implemented at the firm level and examine the employment modes of 76 subsidiaries of US MNCs in a coordinated market economy (Germany), a hybrid market economy (Switzerland) and a liberal market economy (UK). Our results reveal substantial differences in the expatriation strategies of MNCs that depend not only on the international focus of the MNC but also on the differences in IR between the parent and subsidiary's environment. Our findings qualify the role of expatriates in adjusting subsidiaries' employment modes to different market economies and highlight the boundary conditions of integrating HRM with IR practices in the management of foreign subsidiaries.
Chemiresistive Properties of a Novel Composite Comprised of ITO-Nanoparticles and 1,8-Diaminooctane
2018-12-18

Indium-Tin-Oxide (ITO) nanoparticles have been cross-linked with organic 1,8-Diaminooctane (C8A) molecules. The network has been prepared by layer-by-layer self-assembly on substrates with interdigitated electrodes and their sensing properties were studied with vapors of toluene, 1-propanol, water, and 4-methyl-2-pentanone. We demonstrated that the network based chemiresistor shows sensing properties towards volatile organic compounds (VOC).
Spatial Presentations, but Not Response Formats Influence Spatial-Numerical Associations in Adults
2018-12-18

According to theories of embodied numerosity, processing of numerical magnitude is anchored in bodily experiences. In particular, spatial representations of number interact with movement in physical space, but it is still unclear whether the extent of the movement is relevant for this interaction. In this study, we compared spatial-numerical associations over response movements of differing spatial expansion. We expected spatial-numerical effects to increase with the extent of physical response movements. In addition, we hypothesized that these effects should be influenced by whether or not a spatial representation of numbers was presented. Adult participants performed two tasks: a <i>magnitude classification</i> (comparing numbers to the fixed standard 5), from which we calculated the Spatial Numerical Association of Response Codes (SNARC) effect; and a <i>magnitude comparison</i> task (comparing two numbers against each other), from which we calculated a relative numerical congruity effect (NCE), which describes that when two relatively small numbers are compared, responses to the smaller number are faster than responses to the larger number; and vice versa for large numbers. A SNARC effect was observed across all conditions and was not influenced by response movement extent but increased when a number line was presented. In contrast, an NCE was only observed when no number line was presented. This suggests that the SNARC effect and the NCE reflect two different processes. The SNARC effect seems to represent a highly automated classification of numbers as large or small, which is further emphasized by the presentation of a number line. In contrast, the NCE likely results from participants not only classifying numbers as small or large, but also processing their relative size within the relevant section of their mental number line representation. An additional external presentation of a number line might interfere with this process, resulting in overall slower responses. This study follows up on previous spatial-numerical training studies and has implications for future spatial-numerical trainings. Specifically, similar studies with children showed contrasting results, in that response format but not number line presentation influenced spatial-numerical associations. Accordingly, during development, the relative relevance of physical experiences and presentation format for spatial-numerical associations might change.
Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology
2018-12-19

Targeted covalent inhibitors (TCIs) are designed to bind poorly conserved amino acids by means of reactive groups, the so-called warheads. Currently, targeting noncatalytic cysteine residues with acrylamides and other α,β-unsaturated carbonyl compounds is the predominant strategy in TCI development. The recent ascent of covalent drugs has stimulated considerable efforts to characterize alternative warheads for the covalent-reversible and irreversible engagement of noncatalytic cysteine residues as well as other amino acids. This Perspective article provides an overview of warheads-beyond α,β-unsaturated amides-recently used in the design of targeted covalent ligands. Promising reactive groups that have not yet demonstrated their utility in TCI development are also highlighted. Special emphasis is placed on the discussion of reactivity and of case studies illustrating applications in medicinal chemistry and chemical biology.
Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer
2018-12-19

Background: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data sources and study eligibility criteria: A systematic literature search was performed in PubMed, with keywords “HIPEC” and “colorectal cancer”, according to established guidelines. Articles were systematically screened, selecting 87 publications complemented by 48 publications identified through extended search for subsequent synthesis and evaluation, extracting inter alia details on used drugs, dosage, temperature, exposure times, and carrier solutions. Results: Compiled publications contained 171 reports on HIPEC conduct foremost with mitomycin C and oxaliplatin, but also other drugs and drug combinations, comprising at least 60 different procedures. We hence provide an overview of interconnections between HIPEC protocols, used drugs and carrier solutions as well as their volumes. In addition, HIPEC temperatures and dosing benchmarks, as well as an estimate of in vivo resulting drug concentrations are demonstrated. Conclusions and implications: Owing to recent developments, HIPEC conduct and practices need to be reassessed. Unfortunately, imprecise and lacking reporting is frequent, which is why minimal information requirements should be established for HIPEC and the introduction of final drug concentrations for comparability reasons seems sensible.
Human-level saccade detection performance using deep neural networks
2018-12-19

Saccades are ballistic eye movements that rapidly shift gaze from one location of visual space to another. Detecting saccades in eye movement recordings is important not only for studying the neural mechanisms underlying sensory, motor, and cognitive processes, but also as a clinical and diagnostic tool. However, automatically detecting saccades can be difficult, particularly when such saccades are generated in coordination with other tracking eye movements, like smooth pursuits, or when the saccade amplitude is close to eye tracker noise levels, like with microsaccades. In such cases, labeling by human experts is required, but this is a tedious task prone to variability and error. We developed a convolutional neural network to automatically detect saccades at human-level accuracy and with minimal training examples. Our algorithm surpasses state of the art according to common performance metrics and could facilitate studies of neurophysiological processes underlying saccade generation and visual processing. NEW &amp; NOTEWORTHY Detecting saccades in eye movement recordings can be a difficult task, but it is a necessary first step in many applications. We present a convolutional neural network that can automatically identify saccades with human-level accuracy and with minimal training examples. We show that our algorithm performs better than other available algorithms, by comparing performance on a wide range of data sets. We offer an open-source implementation of the algorithm as well as a web service.
Designing zinc oxide nanostructures (nanoworms, nanoflowers, nanowalls, and nanorods) by pulsed laser ablation technique for gas‐sensing application
2018-12-19

Abstract In this study, pulsed laser ablation technique, also known as pulsed laser deposition (PLD), is used to design and grow zinc oxide (ZnO) nanostructures (nanoworms, nanowalls, and nanorods) by template/seeding approach for gas‐sensing applications. Conventionally, ZnO nanostructures used for gas‐sensing have been usually prepared via chemical route, where the 3D/2D nanostructures are chemically synthesized and subsequently plated on an appropriate substrate. However, using pulsed laser ablation technique, the ZnO nanostructures are structurally designed and grown directly on a substrate using a two‐step temperature‐pressure seeding approach. This approach has been optimized to design various ZnO nanostructures by understanding the effect of substrate temperature in the 300‐750°C range under O 2 gas pressure from 10‐mTorr to 10 Torr. Using a thin ZnO seed layer as template that is deposited first at substrate temperature of ~300°C at background oxygen pressure of 10 mTorr on Si(100), ZnO nanostructures, such as nanoworms, nanowalls, and nanorods (with secondary flower‐like growth) were grown at substrate temperatures and oxygen background pressures of (550°C and 2 Torr), (550°C and 0.5 Torr), and (650°C and 2 Torr), respectively. The morphology and the optical properties of ZnO nanostructures were examined by Scanning Electron Microscope (SEM‐EDX), X‐ray Diffraction (XRD), and photoluminescence (PL). The PLD‐grown ZnO nanostructures are single‐crystals and are highly oriented in the c ‐axis. The vapor‐solid (VS) model is proposed to be responsible for the growth of ZnO nanostructures by PLD process. Furthermore, the ZnO nanowall structure is a very promising nanostructure due to its very high surface‐to‐volume ratio. Although ZnO nanowalls have been grown by other methods for sensor application, to this date, only a very few ZnO nanowalls have been grown by PLD for this purpose. In this regard, ZnO nanowall structures are deposited by PLD on an Al 2 O 3 test sensor and assessed for their responses to CO and ethanol gases at 50 ppm, where good responses were observed at 350 and 400°C, respectively. The PLD‐grown ZnO nanostructures are very excellent materials for potential applications such as in dye‐sensitized solar cells, perovskite solar cells and biological and gas sensors.
A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry
2018-12-19

The field of epitranscriptomics is growing in importance, with chemical modification of RNA being associated with a wide variety of biological phenomena. A pivotal challenge in this area is the identification of modified RNA residues within their sequence contexts. Next-generation sequencing approaches are generally unable to capture modifications, although workarounds for some epigenetic marks exist. Mass spectrometry (MS) offers a comprehensive solution by using analogous approaches to shotgun proteomics. However, software support for the analysis of RNA MS data is inadequate at present and does not allow high-throughput processing. In particular, existing software solutions lack the raw performance and statistical grounding to efficiently handle the large variety of modifications present on RNA. We present a free and open-source database search engine for RNA MS data, called NucleicAcidSearchEngine (NASE), that addresses these shortcomings. We demonstrate the capability of NASE to reliably identify a wide range of modified RNA sequences in three original datasets of varying complexity. In a human tRNA sample, we characterize over 20 different modification types simultaneously and find many cases of incomplete modification.
State-dependent geometry of population activity in rat auditory cortex
2018-12-19

Abstract The accuracy of the neural code depends on the relative embedding of signal and noise in the activity of neural populations. Despite a wealth of theoretical work on population codes, there are few empirical characterisations of the high-dimensional signal and noise subspaces. We studied the geometry of population codes in the rat auditory cortex across brain states along the activation-inactivation continuum, using sounds varying in difference and mean level across the ears. As the cortex becomes more activated, single-hemisphere populations go from preferring contralateral loud sounds to a symmetric preference across lateralisations and intensities, gain-modulation effectively disappears, and the signal and noise subspaces become approximately orthogonal to each other and to the direction corresponding to global activity modulations. Level-invariant decoding of sound lateralisation also becomes possible in the active state. Our results provide an empirical foundation for the geometry and state-dependence of cortical population codes.
Assay of β-glucosidase 2 (GBA2) activity using lithocholic acid β-3-O-glucoside substrate for cultured fibroblasts and glucosylceramide for brain tissue
2018-12-19

Abstract Beta (β)-glucosidase 2 (GBA2) is deficient in a form of human spastic paraplegia due to defects in GBA2 ( SPG46 ). GBA2 was proposed as a modifier of Gaucher disease, a lysosomal storage disease resulting from deficient β-glucosidase 1; GBA1. Current GBA2 activity assays using artificial substrates incompletely model the activity encountered in vivo . We studied GBA2 activity, using lithocholic acid β-glucoside or glucosylceramide as natural β-glucosidase substrates in murine tissues or cultured patient fibroblasts with the pathologic genotypes: Gba1 −/− ; Gba2 −/− ; GBA1 −/− ; GBA2 +/− and found expected and unexpected deviations from normal controls.