Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: a meta-analysis of randomized controlled trials

Purpose Hematologic toxicities, including neutropenia, thrombocytopenia, and anemia, are major adverse effects of PARP inhibitors (PARPis), but the incidence rate and overall risk has not been systematically studied. Therefore, we conducted a meta-analysis of published clinical trials to investigate the incidence and relative risks (RRs) of severe (high-grade) hematologic events in cancer patients treated with PARPis. Methods PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were Phase II and III randomized controlled trials (RCTs) of PARPis in cancer patients with adequate safety data on hematologic toxicities. The summary incidence, RRs, and 95% confidence intervals (CIs) were calculated. Results A total of 2,479 patients from 12 RCTs revealed that the incidence of PARPi-associated severe hematologic toxicities was, respectively: neutropenia: 32.9% (95% CI, 20.5%–48.3%); thrombocytopenia: 15.9% (95% CI, 9.5%–25.4%), and anemia: 9.1% (95% CI, 5.1%–15.7%). Olaparib was associated with an increased risk of severe neutropenia. Veliparib was associated with an increased risk of severe neutropenia and thrombocytopenia. Niraparib was associated with an increased risk of severe thrombocytopenia, anemia, and neutropenia. When stratified by combination therapy, significantly increased risk of hematologic toxicities was observed for patients treated with PARPis monotherapy and PARPis combined with single-agent chemotherapy. Conclusion Treatment with PARPis olaparib, veliparib, and niraparib is associated with a significant increase in the risk of hematologic toxicities in cancer patients, and frequent clinical monitoring should be emphasized when managing these PARPis.
Convergence of Gradient Descent on Separable Data

We provide a detailed study on the implicit bias of gradient descent when optimizing loss functions with strictly monotone tails, such as the logistic loss, over separable datasets. We look at two basic questions: (a) what are the conditions on the tail of the loss function under which gradient descent converges in the direction of the $L_2$ maximum-margin separator? (b) how does the rate of margin convergence depend on the tail of the loss function and the choice of the step size? We show that for a large family of super-polynomial tailed losses, gradient descent iterates on linear networks of any depth converge in the direction of $L_2$ maximum-margin solution, while this does not hold for losses with heavier tails. Within this family, for simple linear models we show that the optimal rates with fixed step size is indeed obtained for the commonly used exponentially tailed losses such as logistic loss. However, with a fixed step size the optimal convergence rate is extremely slow as $1/\log(t)$, as also proved in Soudry et al. (2018). For linear models with exponential loss, we further prove that the convergence rate could be improved to $\log (t) /\sqrt{t}$ by using aggressive step sizes that compensates for the rapidly vanishing gradients. Numerical results suggest this method might be useful for deep networks.
RRT-CoLearn: Towards Kinodynamic Planning Without Numerical Trajectory Optimization

Sampling-based kinodynamic planners, such as rapidly-exploring random trees (RRTs), pose two fundamental challenges: computing a reliable (pseudo-)metric for the distance between two random nodes, and computing a steering input to connect the nodes. The core of these challenges is a two point boundary value problem, known to be NP-hard. Recently, the distance metric has been approximated using supervised learning, reducing computation time drastically. Previous work on such learning RRTs use direct optimal control to generate the data for supervised learning. This letter proposes to use indirect optimal control instead, because it provides two benefits: it reduces the computational effort to generate the data, and it provides a low-dimensional parametrization of the action space. The latter allows us to learn both the distance metric and the steering input. This eliminates the need for a local planner in learning RRTs. Experimental results on a pendulum swing up show tenfold speed-up in both the offline data generation and the online planning time.
Study on the prevalence of lipolytic yeasts and moulds in raw cow milk and white brined cheese.

The extent of microbial contamination with moulds and yeasts of raw cow milk and white brined cheese produced in Bulgarian dairy enterprises was evaluated. The isolation and identification of microorganisms was performed using the classical microbiological methods. The samples of raw milk showed 76.6% contamination with moulds, at average amount of 3.4 log10 cfu/mL, maximum of 4.8 log10 cfu/mL. Yeasts were detected in 93.3% of the samples (average 3.5 log10 cfu/mL). Isolated moulds belonged to the genera Aspergillus (37.9%), Geotrichum (29.3%), Mucor (15.5%), Cladosporium (5.2%) and Penicillium (12.1%). Overall, 70% of studied samples were found to be contaminated with yeasts and moulds at 2.2 log10 cfu/g and 2.8 log10 cfu/g, respectively. Most commonly, isolates from white brined cheese were from the genera Geotrichum (32.8%), Aspergillus (28.1%), Mucor (21.8%) and Penicillium (9.4%). The predominating yeasts in raw cow milk and white brined cheese were Candida spp. , Rhodotorula spp. and Sacharomyces spp. Isolates were tested for lipolytic activity on Tributyrin agar. The occurrence of lipolytic and toxigenic moulds and yeasts poses a risk for the quality and safety of milk and dairy products.
Modeling and rehabilitation following anterior cruciate ligament reconstruction

Background/Purpose: This study sought to examine the effectiveness of a modeling video to reduce preoperative perceptions of anxiety and pain, as well as to increase postoperative self-efficacy and functional outcomes after anterior cruciate ligament reconstruction.Methods: Following baseline assessment of state anxiety, perceptions of expected pain, injury severity, and knee function (International Knee Documentation Committee [IKDC] system), patients scheduled for surgical reconstruction of the anterior cruciate ligament were randomly assigned to either a modeling intervention or a control group. Psychological assessments were repeated preoperatively for expected pain and anxiety. Actual pain was assessed preoperatively, prior to discharge, and at 2 weeks postoperatively. Rehabilitation self-efficacy was assessed prior to discharge and at 2 and 6 weeks postoperatively. IKDC functional assessments were repeated at 6 weeks postoperatively, whereas range of motion was assessed at 2 and 6 weeks postsurgery.Results: Compared with the participants in the control condition, participants assigned to the modeling intervention reported significantly lower perceptions of expected pain preoperatively and significantly greater self-efficacy at predischarge to perform rehabilitation tasks. Those who received the modeling intervention also experienced significantly better IKDC objective functional outcome scores compared with their control counterparts. No psychological variables mediated relations between the intervention and functional outcomes.Conclusions: The data suggest that watching a modeling video may be an effective prophylactic treatment to decrease perceptions of expected pain, increase rehabilitation self-efficacy, and provide an early stimulus with respect to early function.
Non‐contrast MR imaging of blood‐brain barrier permeability to water

Many brain diseases are associated with an alteration in blood‐brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non‐contrast MRI technique for the assessment of BBB permeability to water.
The sensory features of a food cue influence its ability to act as an incentive stimulus and evoke dopamine release in the nucleus accumbens core

The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track”; ST), approach to the location of reward delivery (rats that “goal-track”; GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates. ” Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever—dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility.
Combined ALK and MDM2 inhibition increases antitumor activity and overcomes resistance in human ALK mutant neuroblastoma cell lines and xenograft models

The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is limited, highlighting the need to improve their effectiveness in these patients. To this end, we sought to develop a combination strategy to enhance the antitumor activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and xenograft models expressing activated ALK. Herein, we report that combined inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and pro-apoptotic proteins. Consequently, this combination treatment synergistically inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK amplification or mutations in vitro, and resulted in complete and durable responses in neuroblastoma xenografts derived from these cells. We further demonstrate that concurrent inhibition of MDM2 and ALK was able to overcome ceritinib resistance conferred by MYCN upregulation in vitro and in vivo. Together, combined inhibition of ALK and MDM2 may provide an effective treatment for TP53 wild-type neuroblastoma with ALK aberrations. DOI: http://dx.doi. org/10.7554/eLife.17137. 001
Can sub-Saharan Africa feed itself?

Significance The question whether sub-Saharan Africa (SSA) can be self-sufficient in cereals by 2050 is of global relevance. Currently, SSA is amongst the (sub)continents with the largest gap between cereal consumption and production, whereas its projected tripling demand between 2010 and 2050 is much greater than in other continents. We show that nearly complete closure of the gap between current farm yields and yield potential is needed to maintain the current level of cereal self-sufficiency (approximately 80%) by 2050. For all countries, such yield gap closure requires a large, abrupt acceleration in rate of yield increase. If this acceleration is not achieved, massive cropland expansion with attendant biodiversity loss and greenhouse gas emissions or vast import dependency are to be expected. Although global food demand is expected to increase 60% by 2050 compared with 2005/2007, the rise will be much greater in sub-Saharan Africa (SSA). Indeed, SSA is the region at greatest food security risk because by 2050 its population will increase 2.5-fold and demand for cereals approximately triple, whereas current levels of cereal consumption already depend on substantial imports. At issue is whether SSA can meet this vast increase in cereal demand without greater reliance on cereal imports or major expansion of agricultural area and associated biodiversity loss and greenhouse gas emissions. Recent studies indicate that the global increase in food demand by 2050 can be met through closing the gap between current farm yield and yield potential on existing cropland. Here, however, we estimate it will not be feasible to meet future SSA cereal demand on existing production area by yield gap closure alone. Our agronomically robust yield gap analysis for 10 countries in SSA using location-specific data and a spatial upscaling approach reveals that, in addition to yield gap closure, other more complex and uncertain components of intensification are also needed, i.e., increasing cropping intensity (the number of crops grown per 12 mo on the same field) and sustainable expansion of irrigated production area. If intensification is not successful and massive cropland land expansion is to be avoided, SSA will depend much more on imports of cereals than it does today.
Model-Based Real-Time Non-Rigid Tracking

This paper presents a sequential non-rigid reconstruction method that recovers the 3D shape and the camera pose of a deforming object from a video sequence and a previous shape model of the object. We take PTAM (Parallel Mapping and Tracking), a state-of-the-art sequential real-time SfM (Structure-from-Motion) engine, and we upgrade it to solve non-rigid reconstruction. Our method provides a good trade-off between processing time and reconstruction error without the need for specific processing hardware, such as GPUs. We improve the original PTAM matching by using descriptor-based features, as well as smoothness priors to better constrain the 3D error. This paper works with perspective projection and deals with outliers and missing data. We evaluate the tracking algorithm performance through different tests over several datasets of non-rigid deforming objects. Our method achieves state-of-the-art accuracy and can be used as a real-time method suitable for being embedded in portable devices.
Generative statistical models with self-emergent grammar of chord sequences

ABSTRACT Generative statistical models of chord sequences play crucial roles in music processing. To capture syntactic similarities among certain chords (e.g. in C major key, between G and G7 and between F and Dm), we study hidden Markov models and probabilistic context-free grammar models with latent variables describing syntactic categories of chord symbols and their unsupervised learning techniques for inducing the latent grammar from data. Surprisingly, we find that these models often outperform conventional Markov models in predictive power, and the self-emergent categories often correspond to traditional harmonic functions. This implies the need for chord categories in harmony models from the informatics perspective.
A Compound-Plus-Noise Model for Improved Vessel Detection in Non-Gaussian SAR Imagery

The commonly applied K-distribution to model the synthetic aperture radar image amplitude of the heterogeneous (non-Gaussian) sea surface as the basis for vessel detection has shown deficiencies in practical cases, particularly for space-based systems. Due to a deviation between the K-probability density function and measured histograms in the tails, even the inclusion of thermal noise is oftentimes not sufficient to cover the range of environments that are expected. As a consequence, virtually all detectors try to reduce the large number of obtained false detections by relying on rather heuristic postprocessing steps. Consequently, they forfeit the crucial property of a constant false alarm rate. This paper proposes a novel statistical sea clutter model that describes the data more accurately, especially in challenging environments and thermal-noise limited cases. This new model stands out through its numerical simplicity, permitting efficient parameter adaptation thereby enhancing robustness and reducing computational complexity. Accordingly, the presented sea data model has the potential to replace the widely adopted K-distribution as model of choice for future operational applications.
The teacher in the loop: customizing multimodal learning analytics for blended learning

In blended learning scenarios, evidence needs to be gathered from digital and physical spaces to obtain a more complete view of the teaching and learning processes. However, these scenarios are highly heterogeneous, and the varying data sources available in each particular context can condition the accuracy, relevance, interpretability and actionability of the Learning Analytics (LA) solutions, affecting also the user's sense of agency and trust in such solutions. To aid stakeholders in making use of learning analytics, we propose a process to involve teachers in customizing multimodal LA (MMLA) solutions, adapting them to their particular blended learning situation (e.g., identifying relevant data sources and metrics). Since measuring the added value of adopting an LA solution is not straightforward, we also propose a concrete method for doing so. The results obtained from two case studies in authentic, blended computer-supported collaborative learning settings show an improvement in the sensitivity and F1 scores of the customized MMLA solution. Aside from these quantitative improvements, participant teachers reported both an increment in the effort involved, but also increased relevance, understanding and actionability of the results.
Parasympathetic reactivity and disruptive behavior problems in young children during interactions with their mothers and other adults: A preliminary investigation

Parasympathetic nervous system influences on cardiac functions-commonly indexed via respiratory sinus arrhythmia (RSA)-are central to self-regulation. RSA suppression during challenging emotional and cognitive tasks is often associated with better emotional and behavioral functioning in preschoolers. However, the links between RSA suppression and child behavior across various challenging interpersonal contexts remains unclear. The present study experimentally evaluated the relationship between child RSA reactivity to adult (mother vs. study staff) direction and disruptive behavior problems in children ages 3-8 with varying levels of disruptive behavior problems (N = 43). Reduced RSA suppression in the context of mothers' play-based direction was associated with more severe child behavior problems. In contrast, RSA suppression in the context of staff play-based direction was not associated with behavior problems. Findings suggest that the association between RSA suppression and child behavior problems may vary by social context (i.e., mother vs. other adult direction-givers). Findings are discussed in regard to RSA as an indicator of autonomic self-regulation that has relevance to child disruptive behavior problems.
An astroglial basis of major depressive disorder? An overview

Depression is a chronic, recurring, and serious mood disorder that afflicts up to 20% of the global population. The monoamine hypothesis has dominated our understanding of the pharmacotherapy of depression for more than half a century; however, our understanding of the pathophysiology and pathogenesis of major depression has lagged far behind. Astrocytes are the most abundant and versatile cells in the brain, participating in most, if not all, of brain functions as both a passive housekeeper and an active player. Mounting evidence from clinical, preclinical and post‐mortem studies has revealed a decrease in the number or density of astrocytes and morphological and functional astroglial atrophy in patients with major depressive disorder (MDD) and in animal models of depression. Furthermore, currently available antidepressant treatments at least partially exert their therapeutic effects on astrocytes. More importantly, dysfunctional astrocytes lead to depressive‐like phenotypes in animals. Together, current studies point to astroglial pathology as the potential root cause of MDD. Thus, a shift from a neuron‐centric to an astrocyte‐centric cause of MDD has gained increasing attention during the past two decades. Here we will summarize the current evidence supporting the hypothesis that MDD is a disease of astrocyte pathology and highlight previous studies on promising strategies that directly target astrocytes for the development of novel antidepressant treatments.
Enhanced Macroblock Features for Dynamic Background Modeling in H.264/AVC Video Encoded at Low Bitrate

While H.264 is a well-established standard for video surveillance, its high-profile implementation, in particular, has the unique capabilities that pack more visual detail into a given bitrate. Several algorithms exist that detect moving objects from the H.264 bitstream, most of which end up incorrectly classifying the nonstationary or dynamic components (e.g., jitter camera, waving trees, ripples, etc.) of the background as foreground. Moreover, the coarse quantization schemes adopted at constrained bitrates pose new challenges for direct identification of moving objects/targets from the bitstream. This paper focuses on dynamic background modeling for the H.264 video encoded at very low bitrates. To this end, enhanced features of the fundamental coding unit, i.e., the macroblock (MB) are proposed. Based on the temporal statistics of the MB features gathered from initial frames, MBs that potentially contain parts of moving objects are selected in subsequent frames. The selected MBs constitute a coarse segmentation map of the foreground at the MB level. Finally, pixel-level segmentation of the foreground is obtained by comparing pixels constituting the selected MBs with the colocated counterparts of a background frame. Experimental results showing the comparison of bitstreams encoded at strikingly low bitrates are obtained over a diverse set of standardized surveillance sequences.