Miracle-dz/UniFAR-FTUs huggingface dataset:
Trastuzumab cotreatment improves survival of mice with PC‐3 prostate cancer xenografts treated with the GRPR antagonist 177Lu‐DOTAGA‐PEG2‐RM26

Gastrin‐releasing peptide receptors (GRPRs) are overexpressed in prostate cancer and are suitable for targeted radionuclide therapy (TRT). We optimized the bombesin‐derived GRPR‐antagonist PEG2‐RM26 for labeling with 177Lu and further determined the effect of treatment with 177Lu‐labeled peptide alone or in combination with the anti‐HER2 antibody trastuzumab in a murine model. The PEG2‐RM26 analog was coupled to NOTA, NODAGA, DOTA and DOTAGA chelators. The peptide‐chelator conjugates were labeled with 177Lu and characterized in vitro and in vivo. A preclinical therapeutic study was performed in PC‐3 xenografted mice. Mice were treated with intravenous injections (6 cycles) of (A) PBS, (B) DOTAGA‐PEG2‐RM26, (C) 177Lu‐DOTAGA‐PEG2‐RM26, (D) trastuzumab or (E) 177Lu‐DOTAGA‐PEG2‐RM26 in combination with trastuzumab. 177Lu‐DOTAGA‐PEG2‐RM26 demonstrated quantitative labeling yield at high molar activity (450 GBq/μmol), high in vivo stability (5 min pi >98% of radioligand remained when coinjected with phosphoramidon), high affinity to GRPR (KD = 0.4 ± 0.2 nM), and favorable biodistribution (1 hr pi tumor uptake was higher than in healthy tissues, including the kidneys). Therapy with 177Lu‐DOTAGA‐PEG2‐RM26 induced a significant inhibition of tumor growth. The median survival for control groups was significantly shorter than for treated groups (Group C 66 days, Group E 74 days). Trastuzumab together with radionuclide therapy significantly improved survival. No treatment‐related toxicity was observed. In conclusion, based on in vitro and in vivo characterization of the four 177Lu‐labeled PEG2‐RM26 analogs, we concluded that 177Lu‐DOTAGA‐PEG2‐RM26 was the most promising analog for TRT. Radiotherapy using 177Lu‐DOTAGA‐PEG2‐RM26 effectively inhibited tumor growth in vivo in a murine prostate cancer model. Anti‐HER2 therapy additionally improved survival.
Oxygenation of adipose tissue: A human perspective

Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity‐related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole‐body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.
Propofol use in children with allergies to egg, peanut, soybean or other legumes

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri‐operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food‐allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy‐free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy‐free patients, criteria for a possible allergic reaction were met. In nine of the food‐allergic children and in all the controls valid non‐allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.
The RISE 2.0 System: A Case Study in Multistrategy Learning

Several well-developed approaches to inductive learning now exist, but each has speci(cid:12)c limitations that are hard to overcome. Multi-strategy learning attempts to tackle this problem by combining multiple methods in one algorithm. This report describes a uni(cid:12)cation of two widely-used empirical approaches: rule induction and instance-based learning. In the new algorithm, instances are treated as maximally speci(cid:12)c rules, and classi(cid:12)cation is performed using a best-match strategy. Rules are learned by gradually generalizing instances until no improvement in apparent accuracy is obtained. Theoretical analysis shows this approach to be e(cid:14)cient. It is implemented in the RISE 2.0 system. In an extensive empirical study, RISE consistently outperforms state-of-the-art representatives of both its parent approaches (PEBLS and CN2), as well as a decision tree learner (C4.5). Most signi(cid:12)cantly, in 15 of the domains studied, RISE achieves higher accuracy than the best of PEBLS and CN2, showing that a signi(cid:12)cant synergy can be obtained by combining multiple empirical methods.
A neuroanatomical examination of embodied cognition: semantic generation to action-related stimuli

The theory of embodied cognition postulates that the brain represents semantic knowledge as a function of the interaction between the body and the environment. The goal of our research was to provide a neuroanatomical examination of embodied cognition using action-related pictures and words. We used functional magnetic resonance imaging (fMRI) to examine whether there were shared and/or unique regions of activation between an ecologically valid semantic generation task and a motor task in the parietal-frontocentral network (PFN), as a function of stimulus format (pictures versus words) for two stimulus types (hand and foot). Unlike other methods for neuroimaging analyses involving subtractive logic or conjoint analyses, this method first isolates shared and unique regions of activation within-participants before generating an averaged map. The results demonstrated shared activation between the semantic generation and motor tasks, which was organized somatotopically in the PFN, as well as unique activation for the semantic generation tasks in proximity to the hand or foot motor cortex. We also found unique and shared regions of activation in the PFN as a function of stimulus format (pictures versus words). These results further elucidate embodied cognition in that they show that brain regions activated during actual motor movements were also activated when an individual verbally generates action-related semantic information. Disembodied cognition theories and limitations are also discussed.
Classification of occupational therapy intervention for inpatient stroke rehabilitation.

OBJECTIVE We investigated the specific type of occupational therapy intervention used by occupational therapists during inpatient stroke rehabilitation in one midwestern U.S. hospital to determine the frequency of prefunctional versus functional activity use. METHOD A retrospective chart analysis was conducted of clients who received inpatient stroke rehabilitation between January 2003 and June 2004. Type of intervention, intervention strategies, and adaptive equipment use were recorded for each session provided. RESULTS The majority of sessions (65.77%, n = 1,022) consisted of activities that were prefunctional in nature compared with 48.26% (n = 750) that focused on activities of daily living. Musculoskeletal intervention strategies were used in more than half (52.25%) of the sessions. CONCLUSION More sessions were spent on prefunctional than on functional activities, and musculoskeletal intervention strategies were most common. Future research studies are warranted to determine the most effective intervention for this client population.
A Simple Linear Velocity Estimator for High-Precision Motion Control

High-quality low speed motion control calls for precise position and velocity signals. However, velocity estimation based on simple numerical differentiation from the only position measurement may be very erroneous, especially in the low-speed regions. A simple linear velocity estimator is proposed based for high-quality instantaneous velocity estimation, on position measurements only. The proposed estimator is constructed based on the fact that velocity belongs to the chain of kinematic quantities: position and velocity, and numerical integration can provide more stable and accurate results than numerical differentiation in the presence of noise. The main attraction of the new algorithm is that it is very effective as well as in low-speed ranges, high robustness against noise, and easy to implement with simple computation. Both extensive simulations and experimental tests have been performed to verify the effectiveness and efficiency of the proposed approach.
The Dark Halo of NGC 5963 as a Constraint on Dark Matter Self-Interaction at the Low-Velocity Regime

Self-interacting dark matter has been proposed as a hypothesis to explain the shallow central slopes of the density profiles of dark matter halos in galaxies. In order to be consistent with observational studies at scales of galaxy clusters, the cross section should scale inversely with the velocity of collision. In this paper we consider the mass density profile of the halo of the low surface brightness (LSB) galaxy NGC 5963 to place an upper limit on the dark matter cross section for collisions with velocities ~150 km s-1, i.e., at the low-velocity regime. After calibrating against cosmological simulations, we found that the large inferred dark matter concentration and central dark matter density in NGC 5963 are inconsistent with an effective collisional cross section per unit of mass >0.2 cm2 g-1. Corrections were applied in order to account for reduction of the core by the adiabatic contraction caused by cooling baryons. Our limits, which involve a number of simplifying, but always conservative, assumptions, exclude the last permitted interval for velocity-dependent cross sections to explain the flat density core in LSB galaxies. Implications for the nature of dark matter are also discussed.
Relationship between remnant hippocampus and amygdala and memory outcomes after stereotactic surgery for mesial temporal lobe epilepsy

Background and purpose Mesial temporal structures play an important role in human memory. In mesial temporal lobe epilepsy (MTLE), seizure activity is generated from the same structures. Surgery is the definitive treatment for medically intractable MTLE. In addition to standard temporal lobe microsurgical resection, stereotactic radiofrequency amygdalohippocampectomy (SAHE) is used as an alternative MTLE treatment. While memory impairments after standard epilepsy surgery are well known, it has been shown that memory decline is not a feature of SAHE. The aim of the present study was to correlate the volume of the remnant hippocampus and amygdala in patients treated by SAHE with changes in memory parameters. Materials and methods Thirty-seven MTLE patients treated by SAHE (ten right, 27 left) were included. Patients underwent magnetic resonance imaging examinations including hippocampal and amygdalar volumetry and neuropsychological evaluation preoperatively and 1 year after surgery. Results Using Spearman correlation analyses, larger left-sided hippocampal reductions were associated with lower verbal memory performance (ρ=−0.46; P=0.02). On the contrary, improvement of global memory quotient (MQ) was positively correlated with larger right-sided hippocampal reduction (ρ=0.66; P=0.04). Similarly, positive correlations between the extent of right amygdalar reduction and verbal MQ (ρ=0.74; P=0.02) and global MQ change (ρ=0.69; P=0.03) were found. Thus, larger right hippocampal and amygdalar reduction was associated with higher global and verbal MQ change after SAHE. Conclusion Larger left-sided hippocampal reductions were associated with lower verbal memory performance. This finding is in accordance with the material-specific model of human memory, which states that the dominant hemisphere is specialized for the learning and recall of verbal information. We hypothesize that larger right-sided ablations enable the left temporal lobe to support memory more effectively, perhaps as a consequence of epileptiform discharges spreading from remnants of right mesiotemporal structures to the left.
Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa

Background:Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission. Methods:We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site. Results:We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18–29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5–50% of participants, substantially decreasing the number needing testing. Conclusion:Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.
An adaptive nonparametric model for the systematic factors of portfolio credit risk premia

The aim of this paper is to investigate the empirical relationship between daily fluctuations in the risk premium for holding a large diversified credit portfolio, which we approximate by a benchmark credit index, and some tradeable market factors which capture systematic risk. The analysis is based on an adaptive nonparametric modelling approach which allows for the data-driven estimation of the nonlinear dynamic relationship between portfolio credit risk premia and their hypothetical components. Our main finding is that the empirical weights of the systematic factors display sudden jumps during market crises and a less intense timedependent behaviour during normal market conditions. In addition, we find that during market crises the directions of the empirical relationships are often inconsistent with ordinary economic intuition, as they are influenced by the specific circumstances of financial markets distress. JEL Classification: G01, G10, G14, C14, C22.
Ursodeoxycholic acid accelerates bile acid enterohepatic circulation

Ursodeoxycholic acid (UDCA) is the first‐line treatment for primary biliary cholangitis, but its effects on the enterohepatic circulation of bile acid (BA) have been under‐investigated. Therefore, we studied the influence of UDCA on BA enterohepatic circulation in vivo and the mechanisms by which UDCA affects the BA kinetics.
Cohort Alcohol Use in France and the Transition from Use to Alcohol Use Disorder and Remission

ABSTRACT The study aimed to examine the age of onset of stages of alcohol use in the general population, and to estimate the association of cohort use with the probability of transitioning from alcohol use to alcohol use disorder (AUD) and remission. French data (N = 2,894) from the European Study of the Epidemiology of Mental Disorders Survey and collected in 2000 were used. Data on lifetime history of alcohol use and DSM-IV alcohol use disorders, and remission were collected. Nearly every adult has consumed alcohol at least once in their lifetime (92.8%), and among users, 88.3% developed regular use, 6.0% met criteria for abuse and 1.7% for dependence. One-third of the population (32.8%) had used alcohol by the age of 15. Over 85% of cases of regular use were established prior to age 25, as were 61.1% of abuse and 39.4% of dependence cases. The proportion of people in an individual’s age and sex cohort who had already used alcohol by a given age was positively and significantly associated with increased odds of transitioning to each stage examined. The findings highlight sensitive periods of life where persons are at greater risk for transitioning to a higher level of alcohol use, and underscore the importance of cohort use in transition risk.
Location Estimation Using Crowdsourced Spatial Relations

The “crowd” has become a very important geospatial data provider. Specifically, nonexpert users have been providing a wealth of quantitative geospatial data (e.g., geotagged tweets or photos, online). With spatial reasoning being a basic form of human cognition, textual narratives expressing user travel experiences (e.g., travel blogs) would provide an even bigger source of geospatial data. Narratives typically contain qualitative geospatial data in the form of objects and spatial relations (e.g., “St. John’s church is to the North of the Acropolis museum.” The scope of this work is (i) to extract these spatial relations from textual narratives, (ii) to quantify (model) them, and (iii) to reason about object locations based only on the quantified spatial relations. We use information extraction methods to identify toponyms and spatial relations, and we formulate a quantitative approach based on distance and orientation features to represent the latter. Probability density functions (PDFs) for spatial relations are determined by means of a greedy expectation maximization (EM)-based algorithm. These PDFs are then used to estimate unknown object locations. Experiments using a text corpus harvested from travel blog sites establish the considerable location estimation accuracy of the proposed approach on synthetic and real-world scenarios.
Robust Model-Based 3D Head Pose Estimation

We introduce a method for accurate three dimensional head pose estimation using a commodity depth camera. We perform pose estimation by registering a morphable face model to the measured depth data, using a combination of particle swarm optimization (PSO) and the iterative closest point (ICP) algorithm, which minimizes a cost function that includes a 3D registration and a 2D overlap term. The pose is estimated on the fly without requiring an explicit initialization or training phase. Our method handles large pose angles and partial occlusions by dynamically adapting to the reliable visible parts of the face. It is robust and generalizes to different depth sensors without modification. On the Biwi Kinect dataset, we achieve best-in-class performance, with average angular errors of 2.1, 2.1 and 2.4 degrees for yaw, pitch, and roll, respectively, and an average translational error of 5.9 mm, while running at 6 fps on a graphics processing unit.
Genetic dissection of drought and heat‐responsive agronomic traits in wheat

Abstract High yield and wide adaptation are principal targets of wheat breeding but are hindered by limited knowledge on genetic basis of agronomic traits and abiotic stress tolerances. In this study, 277 wheat accessions were phenotyped across 30 environments with non‐stress, drought‐stressed, heat‐stressed, and drought‐heat‐stressed treatments and were subjected to genome‐wide association study using 395 681 single nucleotide polymorphisms. We detected 295 associated loci including consistent loci for agronomic traits across different treatments and eurytopic loci for multiple abiotic stress tolerances. A total of 22 loci overlapped with quantitative trait loci identified by biparental quantitative trait loci mapping. Six loci were simultaneously associated with agronomic traits and abiotic stress tolerance, four of which fell within selective sweep regions. Selection in Chinese wheat has increased the frequency of superior marker alleles controlling yield‐related traits in the four loci during past decades, which conversely diminished favourable genetic variation controlling abiotic stress tolerance in the same loci; two promising candidate paralogous genes colocalized with such loci, thereby providing potential targets for studying the molecular mechanism of stress tolerance–productivity trade‐off. These results uncovering promising alleles controlling agronomic traits and/or multiple abiotic stress tolerances, providing insights into heritable covariation between yield and abiotic stress tolerance, will accelerate future efforts for wheat improvement.
What is the Brillouin zone of an anisotropic photonic crystal

The concept of the Brillouin zone (BZ) in relation to a photonic crystal fabricated in an optically anisotropic material is explored both experimentally and theoretically. In experiment, we used femtosecond laser pulses to excite THz polaritons and image their propagation in lithium niobate and lithium tantalate photonic crystal (PhC) slabs. We directly measured the dispersion relation inside PhCs and observed that the lowest bandgap expected to form at the BZ boundary forms inside the BZ in the anisotropic lithium niobate PhC. Our analysis shows that in an anisotropic material the BZ - defined as the Wigner-Seitz cell in the reciprocal lattice - is no longer bounded by Bragg planes and thus does not conform to the original definition of the BZ by Brillouin. We construct an alternative Brillouin zone defined by Bragg planes and show its utility in identifying features of the dispersion bands. We show that for an anisotropic 2D PhC without dispersion, the Bragg plane BZ can be constructed by applying the Wigner-Seitz method to a stretched or compressed reciprocal lattice. We also show that in the presence of the dispersion in the underlying material or in a slab waveguide, the Bragg planes are generally represented by curved surfaces rather than planes. The concept of constructing a BZ with Bragg planes should prove useful in understanding the formation of dispersion bands in anisotropic PhCs and in selectively tailoring their optical properties.