julilili42/papers huggingface dataset:
Safety and Effectiveness of a 3-Day Rush Insect Venom Immunotherapy Protocol
2019-12-03

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Venom immunotherapy (VIT) is an established and effective treatment for patients with Hymenoptera venom allergies. Especially during the build-up of VIT, systemic allergic reactions are a key issue. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To investigate the safety and effectiveness of a 3-day rush insect VIT protocol and a strategy for the management of individuals with VIT-induced anaphylaxis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this retrospective monocentric study, 11-year data regarding build-up cycles of VIT were retrieved from institutional records. The following parameters of VIT-induced anaphylaxis were analyzed: frequency, severity, time of occurrence within the build-up cycle, and impact on the success of VIT. The effectiveness of VIT was assessed by the results of sting challenges (SCs) by the culprit insect. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In total, 1,317 initial build-up cycles of VIT were evaluated in this study, and the frequency of VIT-induced anaphylaxis was 6.6%. Anaphylaxis occurred most frequently when the daily cumulative venom dose was ≥100 μg. A group (&lt;i&gt;n&lt;/i&gt; = 65) of patients with VIT-induced anaphylaxis in this dose range temporarily received a reduced maintenance dose, and without additional co-medications or complications, the target dose was reached after a second build-up in 91% of the cycles. After completing the VIT build-up, SCs were performed in 76.9% of the cohort, and the effectiveness of VIT was confirmed by 98.5% of the tests. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In this study, we report a 3-day VIT rush protocol with a reasonable rate of VIT-induced anaphylaxis and excellent effectiveness of VIT.
The IL-2RG R328X nonsense mutation allows partial STAT-5 phosphorylation and defines a critical region involved in the leaky-SCID phenotype
2019-12-03

Summary In addition to their detection in typical X-linked severe combined immunodeficiency, hypomorphic mutations in the interleukin (IL)-2 receptor common gamma chain gene (IL2RG) have been described in patients with atypical clinical and immunological phenotypes. In this leaky clinical phenotype the diagnosis is often delayed, limiting prompt therapy in these patients. Here, we report the biochemical and functional characterization of a nonsense mutation in exon 8 (p.R328X) of IL2RG in two siblings: a 4-year-old boy with lethal Epstein–Barr virus-related lymphoma and his asymptomatic 8-month-old brother with a TlowB+natural killer (NK)+ immunophenotype, dysgammaglobulinemia, abnormal lymphocyte proliferation and reduced levels of T cell receptor excision circles. After confirming normal IL-2RG expression (CD132) on T lymphocytes, signal transducer and activator of transcription-1 (STAT-5) phosphorylation was examined to evaluate the functionality of the common gamma chain (γc), which showed partially preserved function. Co-immunoprecipitation experiments were performed to assess the interaction capacity of the R328X mutant with Janus kinase (JAK)3, concluding that R328X impairs JAK3 binding to γc. Here, we describe how the R328X mutation in IL-2RG may allow partial phosphorylation of STAT-5 through a JAK3-independent pathway. We identified a region of three amino acids in the γc intracellular domain that may be critical for receptor stabilization and allow this alternative signaling. Identification of the functional consequences of pathogenic IL2RG variants at the cellular level is important to enable clearer understanding of partial defects leading to leaky phenotypes.
PEN-13: A New Generic 13-Item Questionnaire for Measuring Patient Enablement (German Version)
2019-12-03

Background: The purpose of our study was to develop and psychometrically test a German-language survey instrument that measures patient enablement generically and in greater detail than previous instruments. Methods: A multidisciplinary team developed 13 items to capture individual aspects of patient enablement (PEN-13). A pre-test with 26 subjects was followed by a random sample survey of N = 1168 subjects. An exploratory factor analysis was conducted in a random split-half sample of the data to explore PEN-13’s factor structure; a confirmatory factor analysis was conducted in the validation sample. The internal consistency of the factors was evaluated using Cronbach’s alpha, PEN-13’s construct validity was checked by means of additional hypothesis testing. Results: The two factors self-management and patient-practitioner interaction, detected in the exploratory analysis, were confirmed with a few modifications in the confirmatory factor analysis, with the comparative fit index (CFI) amounting to 0.903. The Cronbach’s alpha values of those two factors amounted to α = 0.90 and α = 0.82, respectively. The correlations of the PEN-13 score with the ’general self-efficacy’ and ’health literacy’ (HLS-EU-Q16) scores further confirmed its construct validity; the respective correlation coefficients amounted to 0.57 and 0.60. Conclusion: The German version of the survey instrument Patient Enablement Scale—13 items (PEN-13) shows acceptable psychometric properties. Practical implications: PEN-13 seems particularly suitable for health services research purposes. We recommend checking the results in another sample as well as evaluating its responsiveness to enablement-enhancing interventions.
Individual differences in dopamine function underlying the balance between model-based and model-free control
2019-12-03

Abstract Reinforcement learning involves a balance between model-free (MF) and model-based (MB) systems. Recent studies suggest that individuals with either pharmacologically enhanced levels of dopamine (DA) or higher baseline levels of DA exhibit more MB control. However, it remains unknown whether such pharmacological effects depend on baseline DA. Here, we investigated whether effects of L-DOPA on the balance of MB/MF control depend on ventral striatal baseline DA. Sixty participants had two functional magnetic resonance imaging (fMRI) scans while performing a two-stage sequential decision-making task under 150 mg L-DOPA or placebo (counterbalanced), followed by a 4-hour 18 F-DOPA positron emission tomography (PET) scan (on a separate occasion). We found an interaction between baseline DA levels and L-DOPA induced changes in MB control. Individuals with higher baseline DA levels showed a greater L-DOPA induced enhancement in MB control. Surprisingly, we found a corresponding drug-by-baseline DA interaction on MF, but not MB learning signals in the ventromedial prefrontal cortex. We did not find a significant interaction between baseline DA levels and L-DOPA effects on MF control or MB/MF balance. In sum, our findings point to a baseline dependency of L-DOPA effects on differential aspects of MB and MF control. Individual differences in DA washout may be an important moderator of L-DOPA effects. Overall, our findings complement the general notion where higher DA levels is related to a greater reliance on MB control. Although the relationship between phasic DA firing and MF learning is conventionally assumed in the animal literature, the relationship between DA and MF control is not as straightforward and requires further clarification.
Picturebooks as objects
2019-12-04

Based on recent studies on materiality, picturebook research, and cognitive studies, this paper investigates how children may perceive picturebooks as objects and their material properties. In this regard, we emphasise three dimensions of picturebooks as objects and relate them to developmental stages. The first dimension concerns the materials the picturebooks are composed of, such as paper, cardboard, wood, plastics, and cloth. The second dimension refers to the type of book, e.g. hardbacks, sets of cardboard sheets, fanfold books, pop-up books, and even hybrid objects such as books which are toys at the same time. Finally, this study focuses on the types of actions that are associated with picturebooks as objects, such as biting, building, piling up, setting up, painting, collecting, and arranging. In sum, we argue that an examination of the cognitive perspective is fundamental for the investigation of the social and cultural aspects of the materiality of picturebooks.
Brain–Machine Interface Induced Morpho-Functional Remodeling of the Neural Motor System in Severe Chronic Stroke
2019-12-04

Brain-machine interfaces (BMI) permit bypass motor system disruption by coupling contingent neuroelectric signals related to motor activity with prosthetic devices that enhance afferent and proprioceptive feedback to the somatosensory cortex. In this study, we investigated neural plasticity in the motor network of severely impaired chronic stroke patients after an EEG-BMI-based treatment reinforcing sensorimotor contingency of ipsilesional motor commands. Our structural connectivity analysis revealed decreased fractional anisotropy in the splenium and body of the corpus callosum, and in the contralesional hemisphere in the posterior limb of the internal capsule, the posterior thalamic radiation, and the superior corona radiata. Functional connectivity analysis showed decreased negative interhemispheric coupling between contralesional and ipsilesional sensorimotor regions, and decreased positive intrahemispheric coupling among contralesional sensorimotor regions. These findings indicate that BMI reinforcing ipsilesional brain activity and enhancing proprioceptive function of the affected hand elicits reorganization of contralesional and ipsilesional somatosensory and motor-assemblies as well as afferent and efferent connection-related motor circuits that support the partial re-establishment of the original neurophysiology of the motor system even in severe chronic stroke.
Late Glacial rapid climate change and human response in the Westernmost Mediterranean (Iberia and Morocco)
2019-12-04

This paper investigates the correlation between climate, environment and human land use in the Westernmost Mediterranean on both sides of the Strait of Gibraltar during the Late Glacial. Using a multi-proxy approach on a sample of 300 sites from the Solutrean and Magdalenian of the Iberian Peninsula and from the Iberomaurusian in Morocco, we find evidence for significant changes in settlement patterns and site density after the Last Glacial Maximum. In Southern Iberia, during Heinrich Stadial 1, hyperarid zones expanded drastically from the south-eastern coast to the West through the Interior. This aridification process heavily affected Magdalenian settlement in the South and caused a strong decline of hunter-gatherer population. Southern Iberia during Heinrich Stadial 1 turned out to be a high-risk environment when compared to Northern Iberia. At the same time, the Late Iberomaurusian of Morocco, although considered to be situated in a high-risk environment as well, experiences an increase of sites and expansion of settlement area.
The role of biotic interactions in determining metal hyperaccumulation in plants
2019-12-04

Abstract Heavy metal hyperaccumulation (MH) is a rare trait found in plant species that inhabit metal‐contaminated soils. Two main hypotheses proposed to explain the selective advantage of MH are the elemental defence hypothesis and elemental allelopathy hypothesis. The elemental defence hypothesis suggests that MH functions as defence against herbivores while the elemental allelopathy hypothesis suggests that MH acts to inhibit the growth of neighbours. Nevertheless, these hypotheses are not likely to be mutually exclusive. Here, we present the first study to test both hypotheses simultaneously. We examined these hypotheses with the Cd hyperaccumulator, Arabidopsis halleri , which inhabits both metalliferous and non‐metalliferous soils, thus providing an opportunity to test the hypotheses of both habitats. Arabidopsis halleri plants originating from several populations in both metalliferous and non‐metalliferous soils were grown in a greenhouse in soils with or without cadmium (Cd). Their leaves were used in a feeding experiment with a specialist herbivore and in a set of leaf‐leachate experiments that tested their effect on seed germination and seedling establishment of species co‐occurring with A. halleri. Finally, a field survey in several A. halleri populations was conducted to compare herbivore load between A. halleri and neighbours from metalliferous versus non‐metalliferous soils. Results of the feeding experiment and field survey suggest that Cd accumulation in A. halleri leaves could provide it with defence against herbivores. Results of the leaf‐leachate experiments reveal that Cd accumulation has no effect on seed germination of neighbouring species but inhibits seedling establishment, particularly of plant species originating from non‐metalliferous soils. Our results suggest that both herbivores and competing neighbours may jointly select for MH in plants. Moreover, MH could provide a selective advantage particularly in non‐metalliferous soils, where neighbouring plants lack metal tolerance. These results highlight the importance of including different origins and populations of both the target species and its neighbouring plant species when studying the ecological role of MH. A free Plain Language Summary can be found within the Supporting Information of this article.
In-situ airborne measurements of atmospheric and sea surfaceparameters related to offshore wind parks in the German Bight
2019-12-04

Abstract. Between 6 September 2016 and 15 October 2017, meteorological measurement flights were conducted above the German Bight in the framework of the project WIPAFF (Wind Park Far Field). The scope of the measurements was to investigate long-range wakes with extent larger than 10 km behind entire wind parks, and to investigate the interaction of wind parks and the marine atmospheric boundary layer. The research aircraft Dornier 128 of TU Braunschweig performed in total 41 measurement flights during different seasons and different stability conditions. The instrumentation consisted of a nose boom with sensors for measuring the wind vector, temperature and humidity, and additionally sensors for characterizing the water surface, a surface temperature sensor, a laser scanner, and two cameras in the visible and infrared wavelength range. A detailed overview of the aircraft, sensors, data post processing and flight patterns is provided here. Further, averaged profiles of atmospheric parameters illustrate the range of conditions. The potential use of the data set is shown by first publications. The data are publicly available in the world data center PANGAEA (https://doi.org/10.1594/PANGAEA.902845, Bärfuss et al., 2019).
Low‐dose cidofovir and conversion to mTOR‐based immunosuppression in polyomavirus‐associated nephropathy
2019-12-04

Abstract Background Polyomavirus‐associated nephropathy (PVAN) remains a relevant complication following kidney transplantation with allograft loss rates of up to 50%. Reduction in overall immunosuppression is a cornerstone of therapy, whereas no specific antiviral regimen has shown conclusive benefit to date. The present case series demonstrates the efficacy of a dual therapeutic approach with low‐dose cidofovir and conversion to mTOR‐based immunosuppression in PVAN. Methods Patients with biopsy‐proven PVAN having received low‐dose cidofovir (0.25 mg/kg) according to the Tübingen Cidofovir Protocol and been converted to mTOR‐based immunosuppression were analyzed retrospectively. Results Twenty‐three patients with a median follow‐up of 2.24 [IQR 1.55‐5.01] years were included in the analysis. Median time to PVAN diagnosis was 268 [IQR 153‐869] days after transplantation. Polyomavirus clearance from plasma was achieved in 78% of patients after a median of 118 [IQR 76‐293] days. Of the 23 patients, nine patients (39%) lost their allograft function during follow‐up, but only three of these (13%) due to PVAN. Fourteen patients (61%) stabilized or improved allograft function. The cidofovir protocol allowed for specific antiviral therapy without adverse nephrotoxicity, even in patients with low allograft function. Conclusions Low‐dose cidofovir and conversion to mTOR‐based immunosuppression allow for effective virus clearance and preservation of allograft function in a high proportion of patients with PVAN and progressive allograft dysfunction and may prolong allograft survival in these patients.
Internal References in Cross-modal Matching: A Global Psychophysical Perspective
2019-12-04

Cross-modal matching builds upon our ability to compare intensities across modalities. For example, we can easily match the brightness of a visual stimulus to the loudness of a tone, and vice versa. The regression effect in cross-modal matching relates to the observation that the intensity of whatever stimulus is adjusted exhibits a tendency toward some mean magnitude, which is interpreted as serving as an internal reference. Internal references, however, are not part of classical psychophysical theory in the tradition of Stevens, but form a key ingredient for the theory of global psychophysics initiated by R. Duncan Luce. The present paper extends and generalizes Luce's theory of what he called cross-dimensional magnitude production (Luce et al., 2010, Psychological Review, 117, 1247-1258) to integrate potentially role-dependent internal references (pertaining to the standard, or the adjusted stimulus) as suggested by the regression effect. The attribute cross-dimensional is more comprehensive than cross-modal, because it also includes intra-modal tasks where stimuli differ in an additional dimension (e.g., loudness of tones of different frequency). Reevaluating the available empirical evidence for magnitude production and matching experiments on the basis of these theoretical developments leads to a coherent picture. The results support role-dependence of internal references in cross-dimensional tasks (intra- or cross-modal), but clearly reject it in intra-dimensional tasks. Moreover, predictions derived from the generalized theory provide a close fit of classical data on cross-modal matching. Further directions for empirical as well as theoretical research are highlighted.
Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial
2019-12-05

PURPOSE In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209 ), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years ( P &lt; .001) and 7.1 years ( P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection &lt; 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.
Ge=B π‐Bonding: Synthesis and Reversible [2+2] Cycloaddition of Germaborenes
2019-12-05

Abstract Phosphine‐stabilized germaborenes featuring an unprecedented Ge=B double bond with short B⋅⋅⋅Ge contacts of 1.886(2) ( 4 ) and 1.895(3) Å ( 5 ) were synthesized starting from an intramolecular germylene–phosphine Lewis pair ( 1 ). After oxidative addition of boron trihalides BX 3 (X=Cl, Br), the addition products were reduced with magnesium and catalytic amounts of anthracene to give the borylene derivatives in yields of 78 % ( 4 ) and 57 % ( 5 ). These halide‐substituted germaborenes were characterized by single‐crystal structure analysis, and the electronic structures were studied by quantum‐chemical calculations. According to an NBO NRT analysis, the dominating Lewis structure contains a Ge=B double bond. The germaborenes undergo a reversible, photochemically initiated [2+2] cycloaddition with the phenyl moiety of a terphenyl substituent at room temperature, forming a complex heterocyclic structure with Ge IV in a strongly distorted coordination environment.
Prevalence and Impact of Type I Sensitization to Alpha-Gal in Patients Consulting an Allergy Unit
2019-12-05

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Alpha-gal syndrome is a complex allergy with high clinical relevance regarding mammalian-derived food and drugs and is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-α-1,3-galactose. As not all alpha-gal sIgE-positive individuals present clinical symptoms upon consumption of mammalian meat, the diagnostic value of alpha-gal sIgE has yet to be clarified. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To investigate the prevalence of alpha-gal-sIgE positivity among allergy patients, examine the impact of tick bites as associated risk factors and determine the diagnostic value of alpha-gal-sIgE positivity. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A retrospective cross-sectional study evaluating patients in the Allergy Unit was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. Exposure to tick bites was assessed by a questionnaire. A receiver operating characteristics (ROC) curve analysis was performed to determine the diagnostic value of alpha-gal sIgE for the diagnosis of alpha-gal syndrome. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In the study population (&lt;i&gt;n&lt;/i&gt; = 1369), the overall prevalence of alpha-gal-sIgE-positive (≥0.10 kU&lt;sub&gt;A&lt;/sub&gt;/L) individuals was 19.9%, and the highest prevalence (30.2%) was found in patients with insect venom allergies. A reported tick bite within the 12 months prior to blood sampling significantly increased the risk of alpha-gal-sIgE positivity (OR 2.084). The ROC curve analysis indicated alpha-gal sIgE ≥0.54 kU&lt;sub&gt;A&lt;/sub&gt;/L as the optimal cutoff point for assessing the diagnostic value of alpha-gal syndrome in allergy patients. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In allergy care settings, alpha-gal-sIgE positivity is a common finding. Alpha-gal sIgE is a sensitive marker in the diagnosis of alpha-gal syndrome but has limited predictive value for the characteristics or severity of this allergy.