julilili42/papers huggingface dataset:
Forest wildflowers bloom earlier as Europe warms: lessons from herbaria and spatial modelling
2022-04-28

Summary Today plants often flower earlier due to climate warming. Herbarium specimens are excellent witnesses of such long‐term changes. However, the magnitude of phenological shifts may vary geographically, and the data are often clustered. Therefore, large‐scale analyses of herbarium data are prone to pseudoreplication and geographical biases. We studied over 6000 herbarium specimens of 20 spring‐flowering forest understory herbs from Europe to understand how their phenology had changed during the last century. We estimated phenology trends with or without taking spatial autocorrelation into account. On average plants now flowered over 6 d earlier than at the beginning of the last century. These changes were strongly associated with warmer spring temperatures. Flowering time advanced 3.6 d per 1°C warming. Spatial modelling showed that, in some parts of Europe, plants flowered earlier or later than expected. Without accounting for this, the estimates of phenological shifts were biased and model fits were poor. Our study indicates that forest wildflowers in Europe strongly advanced their phenology in response to climate change. However, these phenological shifts differ geographically. This shows that it is crucial to combine the analysis of herbarium data with spatial modelling when testing for long‐term phenology trends across large spatial scales.
Brain–Heart Interaction and the Experience of Flow While Playing a Video Game
2022-04-28

The flow state – an experience of complete absorption in an activity – is linked with less self-referential processing and increased arousal. We used the heart-evoked potential (HEP), an index representing brain–heart interaction, as well as indices of peripheral physiology to assess the state of flow in individuals playing a video game. 22 gamers and 21 non-gamers played the video game Thumper for 25 min while their brain and cardiorespiratory signals were simultaneously recorded. The more participants were absorbed in the game, the less they thought about time and the faster time passed subjectively. On the cortical level, the fronto-central HEP amplitude was significantly lower while playing the game compared to resting states before and after the game, reflecting less self-referential processing while playing. This HEP effect corresponded with lower activity during gameplay in brain regions contributing to interoceptive processing. The HEP amplitude predicted the level of absorption in the game. While the HEP amplitude was overall lower during the gaming session than during the resting states, within the gaming session the amplitude of HEP was positively associated with absorption. Since higher absorption was related to higher performance in the game, the higher HEP in more absorbed individuals reflects more efficient brain–heart interaction, which is necessary for efficient game play. On the physiological level, a higher level of flow was associated with increased overall sympathetic activity and less inhibited parasympathetic activity toward the end of the game. These results are building blocks for future neurophysiological assessments of flow.
High infection rates for onchocerciasis and soil-transmitted helminthiasis in children under five not receiving preventive chemotherapy: a bottleneck to elimination
2022-04-28

Abstract Background The current mainstay for control/elimination of onchocerciasis and soil-transmitted helminthiasis (STH) relies on ivermectin- and mebendazole/albendazole-based preventive chemotherapies. However, children under five years of age have been excluded in both research activities and control programs, because they were believed to have insignificant infection rates. There is therefore a need for up-to-date knowledge on the prevalence and intensity of STH and onchocerciasis infections in this age group. This study aimed at assessing the rates and intensities of onchocerciasis and STH infections in children under five years of age who are excluded from ivermectin- or mebendazole/albendazole-based preventive chemotherapies. Methods A series of cross-sectional surveys was conducted in four Health Districts in the Centre and Littoral Regions of Cameroon between 2018 and 2019. All subjects aged 2 to 4 years, were screened for prevalence (or infection rate) and intensity [number of eggs per gram of stool (epg) or number of microfilariae per skin snip (mf/ss)] of STH and onchocerciasis infections respectively using the Kato-Katz and skin snip methodologies. Chi-square and the non-parametric tests (Mann Whitney and Kruskal Wallis) were used to compare infection rates and intensities of infections between Health Districts and genders, respectively. Results A total of 421 children were enrolled in this study. The overall prevalence of onchocerciasis was 6.6% [95% confidence interval ( CI ): 4.3‒9.9], ranging from 3.6% (in the Ntui Health District) to 12.2% (in the Bafia Health District). The intensity of infection ranged from 0.5 to 46 microfilariae per skin snip [median: 5; interquartile range (IQR): 2.25‒8.5]. The overall prevalence of STH was 9.6% (95% CI : 6.5‒13.9), with a high infection rate (29.6%) in the Akonolinga Health District. Two STH species ( Ascaris lumbricoides and Trichuris trichiura ) were found among infected individuals. The median intensities of STH infections were 1,992 epg (IQR: 210‒28,704) and 96 epg (IQR: 48‒168) for A. lumbricoides and T. trichiura, respectively. Conclusions This study reveals that children &lt; 5 years of age are highly infected with STH and onchocerciasis, and could contribute to the spread of these diseases, perpetuating a vicious circle of transmission and hampering elimination efforts. These findings reveal the urgent need to provide (or scale) treatments (likely pediatric formulations) to these preschool-aged children, especially in areas of high transmission, to accelerate efforts to reach WHO 2030 target. Graphical Abstract
Milliarcsecond Astrometry for the Galilean Moons Using Stellar Occultations
2022-04-28

Abstract A stellar occultation occurs when a Solar System object passes in front of a star for an observer. This technique allows the sizes and shapes of the occulting body to be determined with kilometer precision. In addition, this technique constrains the occulting body’s positions, albedos, densities, and so on. In the context of the Galilean moons, these events can provide their best ground-based astrometry, with uncertainties in the order of 1 mas (∼3 km at Jupiter’s distance during opposition). We organized campaigns and successfully observed a stellar occultation by Io (JI) in 2021, one by Ganymede (JIII) in 2020, and one by Europa (JII) in 2019, with stations in North and South America. We also re-analyzed two previously published events: one by Europa in 2016 and another by Ganymede in 2017. We then fit the known 3D shape of the occulting satellite and determine its center of figure. This resulted in astrometric positions with uncertainties in the milliarcsecond level. The positions obtained from these stellar occultations can be used together with dynamical models to ensure highly accurate orbits of the Galilean moons. These orbits can help when planning future space probes aiming at the Jovian system, such as JUICE by ESA and Europa Clipper by NASA. They also allow more efficient planning of flyby maneuvers.
Sustainable human population density in Western Europe between 560.000 and 360.000 years ago
2022-04-28

Abstract The time period between 560 and 360 ka (MIS14 to MIS11) was critical for the evolution of the Neanderthal lineage and the appearance of Levallois technology in Europe. The shifts in the distribution of the human populations, driven by cyclical climate changes, are generally accepted to have played major roles in both processes. We used a dataset of palaeoclimate maps and a species distribution model to reconstruct the changes in the area of Western Europe with suitable environmental conditions for humans during 11 time intervals of the MIS14 to MIS 11 period. Eventually, the maximum sustainable human population within the suitable area during each time interval was estimated by extrapolating the relationship observed between recent hunter-gatherer population density and net primary productivity and applying it to the past. Contrary to common assumptions, our results showed the three Mediterranean Peninsulas were not the only region suitable for humans during the glacial periods. The estimated total sustainable population of Western Europe from MIS14 to MIS11 oscillated between 13,000 and 25,000 individuals. These results offer a new theoretical scenario to develop models and hypotheses to explain cultural and biological evolution during the Middle Pleistocene in Western Europe.
Simulation CT-based radiomics for prediction of response after neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer
2022-04-28

Abstract Background To report on the discriminative ability of a simulation Computed Tomography (CT)-based radiomics signature for predicting response to treatment in patients undergoing neoadjuvant chemo-radiation for locally advanced adenocarcinoma of the rectum. Methods Consecutive patients treated at the Universities of Tübingen (from 1/1/07 to 31/12/10, explorative cohort) and Florence (from 1/1/11 to 31/12/17, external validation cohort) were considered in our dual-institution, retrospective analysis. Long-course neoadjuvant chemo-radiation was performed according to local policy. On simulation CT, the rectal Gross Tumor Volume was manually segmented. A feature selection process was performed yielding mineable data through an in-house developed software (written in Python 3.6). Model selection and hyper-parametrization of the model was performed using a fivefold cross validation approach. The main outcome measure of the study was the rate of pathologic good response, defined as the sum of Tumor regression grade (TRG) 3 and 4 according to Dworak’s classification. Results Two-hundred and one patients were included in our analysis, of whom 126 (62.7%) and 75 (37.3%) cases represented the explorative and external validation cohorts, respectively. Patient characteristics were well balanced between the two groups. A similar rate of good response to neoadjuvant treatment was obtained in in both cohorts (46% and 54.7%, respectively; p = 0.247). A total of 1150 features were extracted from the planning scans. A 5-metafeature complex consisting of Principal component analysis (PCA)-clusters (whose main components are LHL Grey-Level-Size-Zone: Large Zone Emphasis, Elongation, HHH Intensity Histogram Mean, HLL Run-Length: Run Level Variance and HHH Co-occurence: Cluster Tendency) in combination with 5-nearest neighbour model was the most robust signature. When applied to the explorative cohort, the prediction of good response corresponded to an average Area under the curve (AUC) value of 0.65 ± 0.02. When the model was tested on the external validation cohort, it ensured a similar accuracy, with a slightly lower predictive ability (AUC of 0.63). Conclusions Radiomics-based, data-mining from simulation CT scans was shown to be feasible and reproducible in two independent cohorts, yielding fair accuracy in the prediction of response to neoadjuvant chemo-radiation.
Establishment of an In Vitro Scab Model for Investigating Different Phases of Wound Healing
2022-04-28

Chronic wounds are a serious problem in clinical work and a heavy burden for individuals and society. In order to develop novel therapies, adequate model systems for the investigation of wound healing are required. Although in past years different in vitro and in vitro wound healing models have been established, a true human-like model does still not exist. Animal models are limited in their use due to species-specific differences in the skin, a lengthy manufacturing process, experimental costs, and ethical concerns. Both 2D and 3D in vitro models are usually comprised of only one or two skin cell types and fail to capture the reaction between blood cells and skin cells. Thus, our aim was to develop an in vitro scab model to investigate early reactions in the wound healing process. The here established scab model is comprised of HaCaT cells and freshly collected blood from healthy volunteers. The generated scabs were stably cultured for more than 2 weeks. TGF-β signaling is well known to regulate the early phases of wound healing. All three TGF-β isoforms and target genes involved in extracellular matrix composition and degradation were expressed in the in vitro scabs. To validate the in vitro scab model, the effects of either additional stimulation or the inhibition of the TGF-β signaling pathway were investigated. Exogenous application of TGF-β1 stimulated matrix remodeling, which loosened the structure of the in vitro scabs with time, also induced expression of the inhibitory Smad7. Inhibition of the endogenous TGF-β signaling, on the contrary, resulted in a rapid condensation and degranulation of the in vitro scabs. In summary, the here established in vitro scab model can be used to analyze the first phases of wound healing where blood and skin cells interact, as it is viable and responsive for more than 2 weeks.
Numerical analysis of two-dimensional Navier–Stokes equations with additive stochastic forcing
2022-04-28

Abstract We propose and study a temporal and a spatio-temporal discretisation of the two-dimensional stochastic Navier–Stokes equations in bounded domains supplemented with no-slip boundary conditions. Considering additive noise, we base its construction on the related nonlinear random partial differential equation, which is solved by a transform of the solution of the stochastic Navier–Stokes equations. We show a strong rate (up to) in probability for a corresponding discretisation in space and time (and space-time).
Examining lecture and inquiry-based laboratory performance for language minority students in science gateway courses
2022-04-28

This study examined the effectiveness of lectures and inquiry-based instruction in supporting learning for language minority (LM) students in science gateway courses at a large public research university. Utilizing institutional data from 6,911 students across nine years, we fitted cross–lagged panel designs to model associations between lecture courses and inquiry-based laboratory courses for both LM and non-LM students in two-course sequences of introductory college Physics and Chemistry. We found that initial performance in lectures and laboratory sessions can be a predictor of subsequent course performance across disciplines and independent of LM status. Notably, while LM students performed worse in the initial lecture course, LM status resulted in neither worse performance in inquiry-based laboratory courses nor in worse performance in subsequent courses in the science gateway course sequence. Thus, this study suggests that interventions intended to support LM students in college science should target the initial courses in the corresponding science gateway course sequences.
High-resolution Neutron Spectroscopy to Study Picosecond-nanosecond Dynamics of Proteins and Hydration Water
2022-04-28

Neutron scattering offers the possibility to probe the dynamics within samples for a wide range of energies in a nondestructive manner and without labeling other than deuterium. In particular, neutron backscattering spectroscopy records the scattering signals at multiple scattering angles simultaneously and is well suited to study the dynamics of biological systems on the ps-ns timescale. By employing D2O-and possibly deuterated buffer components-the method allows monitoring of both center-of-mass diffusion and backbone and side-chain motions (internal dynamics) of proteins in liquid state. Additionally, hydration water dynamics can be studied by employing powders of perdeuterated proteins hydrated with H2O. This paper presents the workflow employed on the instrument IN16B at the Institut Laue-Langevin (ILL) to investigate protein and hydration water dynamics. The preparation of solution samples and hydrated protein powder samples using vapor exchange is explained. The data analysis procedure for both protein and hydration water dynamics is described for different types of datasets (quasielastic spectra or fixed-window scans) that can be obtained on a neutron backscattering spectrometer. The method is illustrated with two studies involving amyloid proteins. The aggregation of lysozyme into μm sized spherical aggregates-denoted particulates-is shown to occur in a one-step process on the space and time range probed on IN16B, while the internal dynamics remains unchanged. Further, the dynamics of hydration water of tau was studied on hydrated powders of perdeuterated protein. It is shown that translational motions of water are activated upon the formation of amyloid fibers. Finally, critical steps in the protocol are discussed as to how neutron scattering is positioned regarding the study of dynamics with respect to other experimental biophysical methods.
Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications
2022-04-29

Abstract We conducted a single-arm, phase 2 trial (German-Austrian Acute Myeloid Leukemia Study Group [AMLSG] 16-10) to evaluate midostaurin with intensive chemotherapy followed by allogeneic hematopoietic-cell transplantation (HCT) and a 1-year midosta urin maintenance therapy in adult patients with acute myeloid leukemia (AML) and fms-related tyrosine kinase 3 (FLT3) internal tandem duplication (ITD). Patients 18 to 70 years of age with newly diagnosed FLT3-ITD-positive AML were eligible. Primary and key secondary endpoints were event-free survival (EFS) and overall survival (OS). Results were compared with a historical cohort of 415 patients treated on 5 prior AMLSG trials; statistical analysis was performed using a double-robust adjustment with propensity score weighting and covariate adjustment. Results were also compared with patients (18-59 years) treated on the placebo arm of the Cancer and Leukemia Group B (CALGB) 10603/RATIFY trial. The trial accrued 440 patients (18-60 years, n = 312; 61-70 years, n = 128). In multivariate analysis, EFS was significantly in favor of patients treated within the AMLSG 16-10 trial compared with the AMLSG control (hazard ratio [HR], 0.55; P &amp;lt; .001); both in younger (HR, 0.59; P &amp;lt; .001) and older patients (HR, 0.42; P &amp;lt; .001). Multivariate analysis also showed a significant beneficial effect on OS compared with the AMLSG control (HR, 0.57; P &amp;lt; .001) as well as to the CALGB 10603/RATIFY trial (HR, 0.71; P = .005). The treatment effect of midostaurin remained significant in sensitivity analysis including allogeneic HCT as a time-dependent covariate. Addition of midostaurin to chemotherapy was safe in younger and older patients. In comparison with historical controls, the addition of midostaurin to intensive therapy led to a significant improvement in outcome in younger and older patients with AML and FLT3-ITD. This trial is registered at clinicaltrialsregistry.eu as Eudra-CT number 2011-003168-63 and at clinicaltrials.gov as NCT01477606.
Distinct ensembles in the noradrenergic locus coeruleus are associated with diverse cortical states
2022-04-29

Significance Brainstem locus coeruleus (LC) noradrenergic neurons produce an arousal-related state characterized by a broadband increase in high-frequency oscillations. This perspective was built upon electrical or optogenetic stimulation that artificially activates LC neurons synchronously. This has led to the conceptual model that LC activation is associated with a single cortical state. Here, we show that natural, spontaneously occurring LC single-unit activity consists of ensembles with largely nonoverlapping activation dynamics. Spontaneous activations of different LC ensembles are associated with different cortical states. Our results suggest that the role of the LC in controlling a single type of cortical state associated with arousal is an oversimplification. Instead, ensembles of LC neurons may control a diverse multitude of cortical states.
Effects, capabilities, and boxes: from scope-based reasoning to type-based reasoning and back
2022-04-29

Reasoning about the use of external resources is an important aspect of many practical applications. Effect systems enable tracking such information in types, but at the cost of complicating signatures of common functions. Capabilities coupled with escape analysis offer safety and natural signatures, but are often overly coarse grained and restrictive. We present System C, which builds on and generalizes ideas from type-based escape analysis and demonstrates that capabilities and effects can be reconciled harmoniously. By assuming that all functions are second class, we can admit natural signatures for many common programs. By introducing a notion of boxed values, we can lift the restrictions of second-class values at the cost of needing to track degree-of-impurity information in types. The system we present is expressive enough to support effect handlers in full capacity. We practically evaluate System C in an implementation and prove its soundness.
Evaluating ensemble post‐processing for wind power forecasts
2022-04-29

Abstract Capturing the uncertainty in probabilistic wind power forecasts is challenging, especially when uncertain input variables, such as the weather, play a role. Since ensemble weather predictions aim to capture the uncertainty in the weather system, they can be used to propagate this uncertainty through to subsequent wind power forecasting models. However, as weather ensemble systems are known to be biassed and underdispersed, meteorologists post‐process the ensembles. This post‐processing can successfully correct the biasses in the weather variables but has not been evaluated thoroughly in the context of subsequent forecasts, such as wind power generation forecasts. The present paper evaluates multiple strategies for applying ensemble post‐processing to probabilistic wind power forecasts. We use Ensemble Model Output Statistics (EMOS) as the post‐processing method and evaluate four possible strategies: only using the raw ensembles without post‐processing, a one‐step strategy where only the weather ensembles are post‐processed, a one‐step strategy where we only post‐process the power ensembles and a two‐step strategy where we post‐process both the weather and power ensembles. Results show that post‐processing the final wind power ensemble improves forecast performance regarding both calibration and sharpness whilst only post‐processing the weather ensembles does not necessarily lead to increased forecast performance.