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ΔMNT, but not MNT and ENT, was significantly larger in controls (2.3 ± 0.9 N) than in NeuP (-0.2 ± 0.7 N). The percentage of dogs with facilitatory sensory profile was similar at baseline and after placebo (61.5-63%), and between controls and after gabapentin (33.3-34.6%). The CBPI scores were significantly different between gabapentin (CBPI pain and CBPI overall impression) and/or gabapentin-meloxicam (CBPI pain and interference) when compared with baseline, but not placebo. The CBPI scores were not significantly different between placebo and baseline. The concentration of cytokines was not different between groups or treatments. Dogs with NeuP have deficient inhibitory pain mechanisms. Pain burden was reduced after gabapentin and/or gabapentin-meloxicam when compared with baseline using CBPI and CMPS-SF scores. However, these scores were not superior than placebo, nor placebo was superior to baseline evaluations. A caregiver placebo effect may have biased the results.

Radiation-induced lymphopenia (RIL) occurs during treatment with conventional radiation in multiple organ sites. Development of RIL portends poor prognosis. Stereotactic body radiation therapy (SBRT) spares RIL in pancreatic cancer, but has not been examined in other sites commonly treated with SBRT. This work examines if SBRT similarly spares RIL in patients with non-small cell lung cancer (NSCLC).

Retrospective analysis was done at a single institution on 40 distinct cases of SBRT for early stage NSCLC from 2006-2017. Incidentally collected lymphocyte counts collected within 6 months of SBRT treatment were analyzed to determine if RIL occurred. The presence of RIL was correlated with location of initial failure and survival endpoints. Kaplan-Meier curves were constructed with significance defined at the level p < 0.05.

RIL was observed in 35% of the analyzed patients. Patterns of failure and survival data were comparable to prior SBRT literature. There was no observed association in two year local, nodal, or distant failure, progression free survival, or overall survival based on the presence of RIL.

SBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents further analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.

SBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents further analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.Perceptual organization is the process of grouping scene elements into whole entities. A classic example is contour integration, in which separate line segments are perceived as continuous contours. Uncertainty in such grouping arises from scene ambiguity and sensory noise. Some classic Gestalt principles of contour integration, and more broadly, of perceptual organization, have been re-framed in terms of Bayesian inference, whereby the observer computes the probability that the whole entity is present. Previous studies that proposed a Bayesian interpretation of perceptual organization, however, have ignored sensory uncertainty, despite the fact that accounting for the current level of perceptual uncertainty is one of the main signatures of Bayesian decision making. Crucially, trial-by-trial manipulation of sensory uncertainty is a key test to whether humans perform near-optimal Bayesian inference in contour integration, as opposed to using some manifestly non-Bayesian heuristic. We distinguish between these hypotheses in a simplified form of contour integration, namely judging whether two line segments separated by an occluder are collinear. We manipulate sensory uncertainty by varying retinal eccentricity. A Bayes-optimal observer would take the level of sensory uncertainty into account-in a very specific way-in deciding whether a measured offset between the line segments is due to non-collinearity or to sensory noise. We find that people deviate slightly but systematically from Bayesian optimality, while still performing "probabilistic computation" in the sense that they take into account sensory uncertainty via a heuristic rule. Our work contributes to an understanding of the role of sensory uncertainty in higher-order perception.

Few tools are available to predict tumor response to treatment. This retrospective study assesses visual and automatic heterogeneity from 18F-FDG PET images as predictors of response in locally advanced rectal cancer.

This study included 37 LARC patients who underwent an 18F-FDG PET before their neoadjuvant therapy. One expert segmented the tumor from the PET images. Blinded to the patient´s outcome, two experts established by consensus a visual score for tumor heterogeneity. Metabolic and texture parameters were extracted from the tumor area. Multivariate binary logistic regression with cross-validation was used to estimate the clinical relevance of these features. Area under the ROC Curve (AUC) of each model was evaluated. Histopathological tumor regression grade was the ground-truth.

Standard metabolic parameters could discriminate 50.1% of responders (AUC = 0.685). Visual heterogeneity classification showed correct assessment of the response in 75.4% of the sample (AUC = 0.759). Automatic quantitative evaluation of heterogeneity achieved a similar predictive capacity (73.1%, AUC = 0.815).

A response prediction model in LARC based on tumor heterogeneity (assessed either visually or with automatic texture measurement) shows that texture features may complement the information provided by the metabolic parameters and increase prediction accuracy.

A response prediction model in LARC based on tumor heterogeneity (assessed either visually or with automatic texture measurement) shows that texture features may complement the information provided by the metabolic parameters and increase prediction accuracy.In contrast to the vast majority of research that has focused on the immediate effects of ionizing radiation, this work concentrates on the molecular mechanism driving delayed effects that emerge in the progeny of the exposed cells. We employed functional protein arrays to identify molecular changes induced in a human bronchial epithelial cell line (HBEC3-KT) and osteosarcoma cell line (U2OS) and evaluated their impact on outcomes associated with radiation induced genomic instability (RIGI) at day 5 and 7 post-exposure to a 2Gy X-ray dose, which revealed replication stress in the context of increased FOXM1b expression. Irradiated cells had reduced DNA replication rate detected by the DNA fiber assay and increased DNA resection detected by RPA foci and phosphorylation. Irradiated cells increased utilization of homologous recombination-dependent repair detected by a gene conversion assay and DNA damage at mitosis reflected by RPA positive chromosomal bridges, micronuclei formation and 53BP1 positive bodies in G1, all known outcomes of replication stress. Interference with the function of FOXM1, a transcription factor widely expressed in cancer, employing an aptamer, decreased radiation-induced micronuclei formation and cell transformation while plasmid-driven overexpression of FOXM1b was sufficient to induce replication stress, micronuclei formation and cell transformation.

Alzheimer's disease and related dementias (ADRD) affect over 5.7 million Americans and over 35 million people worldwide. Detection of mild cognitive impairment (MCI) and early ADRD is a challenge to clinicians and researchers. Brief assessment tools frequently emphasize memory impairment, however executive dysfunction may be one of the earliest signs of impairment. To address the need for a brief, easy-to-score, open-access test of executive function for use in clinical practice and research, we created the Number Symbol Coding Task (NSCT).

This study analyzed 320 consecutive patient-caregiver dyads who underwent a comprehensive evaluation including the Clinical Dementia Rating (CDR), patient and caregiver versions of the Quick Dementia Rating System (QDRS), caregiver ratings of behavior and function, and neuropsychological testing, with a subset undergoing volumetric magnetic resonance imaging (MRI). Estimates of cognitive reserve were calculated using education, combined indices of education and occupata brief fashion that could facilitate its use in clinical care and research.Pre-mRNA splicing is critical for achieving required amounts of a transcript at a given time and for regulating production of encoded protein. A given pre-mRNA may be spliced in many ways, or not at all, giving rise to multiple gene products. NG25 mouse Numerous splicing factors are recruited to pre-mRNA splice sites to ensure proper splicing. One such factor, the 60 kDa poly(U)-binding splicing factor (PUF60), is recruited to sites that are not always spliced, but rather function as alternative splice sites. In this study, we characterized the interaction of PUF60 with a splice site from the adenovirus major late promoter (the AdML 3' splice site, AdML3'). We found that the PUF60-AdML3' dissociation constants are in the micromolar range, with the binding affinity predominantly provided by PUF60's two central RNA recognition motifs (RRMs). A 1.95 Å crystal structure of the two PUF60 RRMs in complex with AdML3' revealed a dimeric organization placing two stretches of nucleic acid tracts in opposing directionalities, which can cause looping of nucleic acid and explain how PUF60 affects pre-mRNA geometry to effect splicing. Solution characterization of this complex by light-scattering and UV/Vis spectroscopy suggested a potential 21 (PUF602AdML3') stoichiometry, consistent with the crystal structure. This work defines the sequence specificity of the alternative splicing factor PUF60 at the pre-mRNA 3' splice site. Our observations suggest that control of pre-mRNA directionality is important in the early stage of spliceosome assembly, and advance our understanding of the molecular mechanism by which alternative and constitutive splicing factors differentiate among 3' splice sites.Ecosystem effects of bottom trawl fisheries are of major concern. Although it is prohibited to catch fish using electricity in European Union waters, a number of beam trawlers obtained a derogation and switched to pulse trawling to explore the potential to reduce impacts. Here we analyse whether using electrical rather than mechanical stimulation results in an overall reduction in physical disturbance of the seafloor in the beam-trawl fishery for sole Solea solea. We extend and apply a recently developed assessment framework to the Dutch beam-trawl fleet and show that the switch to pulse trawling substantially reduced benthic impacts when exploiting the total allowable catch of sole in the North Sea. Using Vessel Monitoring by Satellite and logbook data from 2009 to 2017, we estimate that the trawling footprint decreased by 23%, the precautionary impact indicator of the benthic community decreased by 39%, the impact on median longevity of the benthic community decreased by 20%, the impact on benthic biomass decreased by 61%, and the amount of sediment mobilised decreased by 39%.