Miracle-dz/UniFAR-FTUs huggingface dataset:
Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR-Mutant NSCLC

Purpose: Osimertinib was initially approved for T790M-positive non–small cell lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. Experimental Design: Using cohorts from The University of Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer databases, we collected clinical data for patients treated with osimertinib. Molecular profiling analysis was performed at the time of progression in a subset of the patients. Results: In the 118 patients treated with osimertinib, 42 had molecular profiling at progression. T790M was preserved in 21 (50%) patients and lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common resistance mechanism and were observed exclusively in T790M-preserved cases. MET amplification was the second most common alteration (14%). Recurrent alterations were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition as potential resistance drivers. Alterations of cell-cycle genes were associated with shorter median progression-free survival (PFS, 4.4 vs. 8.8 months, P = 0.01). In 76 patients with progression, osimertinib was continued in 47 cases with a median second PFS (PFS2) of 12.6 months; 21 patients received local consolidation radiation with a median PFS of 15.5 months. Continuation of osimertinib beyond progression was associated with a longer overall survival compared with discontinuation (11.2 vs. 6.1 months, P = 0.02). Conclusions: Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib after progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients. See related commentary by Devarakonda and Govindan, p. 6112.
Reliability and reproducibility of the method of assessment of midpalatal suture maturation: A tomographic study.

OBJECTIVES: To assess reliability and reproducibility of the individual assessment of midpalatal suture maturation in computed tomography among orthodontists and radiologists for potential diagnosis application. MATERIALS AND METHODS: Sixty axial slices from cone-beam computed tomography and multi-slice CT scans of patients aged between 11 and 21 years old (33 females and 27 males) were selected. For the investigation of reliability and reproducibility of the method, two groups of examiners were established. The first group consisted of 11 orthodontists and the second consisted of 10 radiologists. Each group examined the images and performed individual assessment of the midpalatal suture maturation method twice within an interval of 21 days. During the first and second analyses, the sequence of images was randomized to reduce potential bias. Weighted Cohen's kappa was performed to assess inter- and intra-examiners' agreement. The percentage of perfect agreement and the number of stages apart for each disagreement were calculated. The significance level was P < . 05. RESULTS: The overall inter-examiner agreement was satisfactory in the first (kappaw: 0.37) and the second (kappaw: 0.34) analyses. Intra-examiner agreement outcomes were similar between orthodontists (kappaw: 0.44) and radiologists (kappaw: 0.41). The percentage of perfect agreement was 43.2%. CONCLUSIONS: The method for individual assessment of midpalatal suture maturation revealed potential reliability and reproducibility. However, the agreement rate observed in the present study was not high enough for a method designed for routine clinical applications.
A qualitative study exploring the experiences of mindfulness training in people with acquired brain injury

ABSTRACT Recently, there has been increased interest in using mindfulness-based interventions (MBIs) in brain injury rehabilitation. However, no previous qualitative research has explored the experiences of individuals with acquired brain injury (ABI) receiving these interventions. The present study, therefore, aimed to explore how individuals with ABI make sense of their experiences of learning mindfulness skills. Six focus group interviews were conducted with 14 participants with ABI after they had completed an eight-week mindfulness group. The group interviews were transcribed verbatim and analysed using Interpretative Phenomenological Analysis (IPA). Four themes provided in-depth information about participants’ lived experiences of mindfulness training and being in the group; “Developmental learning process”, “Group as a supportive environment for learning”, “Increased awareness” and “Benefits of mindfulness”. The accounts capture participants’ journeys through the process of learning mindfulness skills and implementing them in their everyday lives. The findings also suggested that most participants considered mindfulness beneficial in terms of helping them to cope with the emotional and cognitive consequences of ABI.
Presence of carbapenem-resistant bacteria in soils affected by illegal waste dumps

ABSTRACT The carbapenem-resistant bacteria (CRB) are currently at the top of the WHO priority list of bacteria that pose the greatest threat to human health. Considering that soil is one of the important environments for the emergence of antibiotic-resistant bacteria, we isolated and quantified cultivable CRB in soils across Croatia, including ones affected by illegal dumps. We cultivated CRB at two temperatures, distinguishing between the intrinsically resistant CRB (37°C, mostly Stenotrophomonas spp.) and the ones that are presumably human-associated and clinically relevant (42°C, Acinetobacter sp., Enterobacteriaceae, Burkholderia spp.). Our study demonstrated that distinguishing between the two offers a better insight into the diversity of CRB in the environment. The ones cultivated at 37°C were found in almost all soil samples, while the presumably clinically relevant ones were absent from uncontaminated pasture and grassland, indicating that human-associated CRB are unlikely to be found in soils spared from anthropogenic influence.
Bidirectional Attentional Encoder-Decoder Model and Bidirectional Beam Search for Abstractive Summarization

Sequence generative models with RNN variants, such as LSTM, GRU, show promising performance on abstractive document summarization. However, they still have some issues that limit their performance, especially while deal-ing with long sequences. One of the issues is that, to the best of our knowledge, all current models employ a unidirectional decoder, which reasons only about the past and still limited to retain future context while giving a prediction. This makes these models suffer on their own by generating unbalanced outputs. Moreover, unidirec-tional attention-based document summarization can only capture partial aspects of attentional regularities due to the inherited challenges in document summarization. To this end, we propose an end-to-end trainable bidirectional RNN model to tackle the aforementioned issues. The model has a bidirectional encoder-decoder architecture; in which the encoder and the decoder are bidirectional LSTMs. The forward decoder is initialized with the last hidden state of the backward encoder while the backward decoder is initialized with the last hidden state of the for-ward encoder. In addition, a bidirectional beam search mechanism is proposed as an approximate inference algo-rithm for generating the output summaries from the bidi-rectional model. This enables the model to reason about the past and future and to generate balanced outputs as a result. Experimental results on CNN / Daily Mail dataset show that the proposed model outperforms the current abstractive state-of-the-art models by a considerable mar-gin.
Dreams of Higher Education in the Mediterrani School Through Family Education

Through Learning Communities, schools and their communities may play a key role in overcoming inequalities suffered by vulnerable populations. Learning Communities implement Successful Educational Actions (SEAs), one of which is Family Education. This action focuses on promoting basic education among community members, in addition to other adult educational and cultural activities. In this context, SALEACOM. Overcoming inequalities in schools and Learning Communities: Innovative education for a new century (2015-2017) is a Marie Curie RISE project to develop interdisciplinary solutions for and with learners most heavily affected by inequalities, including access to higher education and its quality. In this article, we focus on one experience from the Mediterrani School (Spain), where we work through SALEACOM. This school was known as a ghetto school until 2012, when they decided to transform the school into a Learning Community and to apply SEAs. This article analyses the impact of the Family Education programme in relation to families and children’s expectations of higher education and how these expectations affected children’s results. Family Education started in the Mediterrani School in the academic year 2012-2013, when the school and families conducted adult training courses. Three years later, family education had a massive response from the community, when 63 community members, 41% of the Roma enrolled in training courses. Since then, all courses are established according to the community’s decisions through their active participation. Following a communicative methodology, we conducted semi-structured interviews with a communicative orientation among some of the participants in these adult courses. The communicative analysis showed that Family Education allowed the participants, and the members of community expected continued education throughout life and access to the university. The Adult Education promoted in the Mediterrani School can have a transformative effect on educational outcomes, opening possibilities for personal and social change.
Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic Performance

Introduction: Cobalt ions (Co2+) stabilize HIFα and increase endogenous erythropoietin (EPO) production creating the possibility that Co2+ supplements (CoSupp) may be used as performance enhancing substances. The aim of this study was to determine the effects of a small oral dosage of CoSupp on hemoglobin mass (Hbmass) and performance with the objective of providing the basis for establishing upper threshold limits of urine [Co2+] to detect CoSupp misuse in sport. Methods: Twenty-four male subjects participated in a double-blind placebo-controlled study. Sixteen received an oral dose of 5 mg of ionized Co2+ per day for 3 weeks, and eight served as controls. Blood and urine samples were taken before the study, during the study and up to 3 weeks after CoSupp. Hbmass was determined by the CO-rebreathing method at regular time intervals, and VO2max was determined before and after the CoSupp administration period. Results: In the Co2+ group, Hbmass increased by 2.0 ± 2.1% (p < 0.001) while all the other analyzed hematological parameters did not show significant interactions of time and treatment. Hemoglobin concentration ([Hb]) and hematocrit (Hct) tended to increase (p = 0.16, p = 0.1) and also [EPO] showed a similar trend (baseline: 9.5 ± 3.0, after 2 weeks: 12.4 ± 5.2 mU/ml). While mean VO2max did not change, there was a trend for a positive relationship between changes in Hbmass and changes in VO2max immediately after CoSupp (r = 0.40, p = 0.11). Urine [Co2+] increased from 0.4 ± 0.3 to 471.4 ± 384.1 ng/ml (p < 0.01) and remained significantly elevated until 2 weeks after cessation. Conclusion: An oral Co2+ dosage of 5 mg/day for 3 weeks effectively increases Hbmass with a tendency to increase hemoglobin concentration ([Hb]) and hematocrit (Hct). Because urine Co2+ concentration remains increased for 2 weeks after cessation, upper limit threshold values for monitoring CoSupp can be established.
First Report of Two Cephalobidae Species(Nematoda: Cephalobomorpha) in South Korea

Cephalobus aff. quinilineatus (Shavrov, 1968) Anderson and Hooper, 1970 and Eucephalobus hooperi MarinariPalmisano, 1967 from the family Cephalobidae Filipjev, 1934 (Cephalobomorpha) are newly reported from South Korea. Cephalobus aff. quinilineatus is distinguished from other Cephalobus species by its high and rounded labial probolae and five lateral incisures, with three incisures extending to the tail terminus. Eucephalobus hooperi is distinguished from other Eucephalobus species by its three bifurcated labial probolae with pointed termini and by morphometric characters such as body and tail length and the corpus:isthmus ratio. In this study, the morphological characters and morphometrics of C. aff. quinilineatus and E. hooperi Korean population are described and illustrated based on optical and/or scanning electron microscopy.
A comprehensive analysis of Local Binary Convolutional Neural Network for fast face recognition in surveillance video

Recent research in convolutional neural network (CNN) has provided a variety of new architectures for deep learning. One interesting new architecture is the local binary convolutional neural network (LBCNN), which has shown to provide significant reduction in the number of parameters to be learned at training. In this paper, we study the influence of network parameters in the scenario of face recognition, comparing LBCNN against other famous networks available in the literature in terms of sensibility and processing time. In our study, we also propose a pre-processing step on images to increase the accuracy of the model, besides investigating its behaviour with noisy images. Our experiments are carried on the Chokepoint dataset, whose face subimages were collected from video frames under real-world surveillance conditions, including variations in terms of illumination, sharpness, pose, and misalignment due to automatic face detection. The conclusion is that by using the Laplacian step and a reduced amount of LBC modules, it is possible to train LBCNN more quickly and with improved accuracy. In addition, it was found that LBCNN is very sensitive to noise and better results can be achieved when noisy images are inserted in the training set.
Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?

Among movement disorders and medicine in general, PD is one of the conditions for which there is a greater knowledge of the placebo and nocebo responses. In other movement disorders, the knowledge of placebo and nocebo responses is less. An advance in this field is expected to contribute to a better understanding of the nature of a therapeutic benefit in clinical research and clinical practice, and mechanisms of placebo and nocebo. We conducted a review on placebo and nocebo responses in other movement disorders besides PD by primarily examining meta‐analyses of clinical trials assessing specifically the placebo and/or nocebo responses. Second, we examined both efficacy and safety results of a placebo arm in pivotal placebo‐controlled trials for the different movement disorders. RLS is the movement disorder for which the most data exist, followed by tic disorders and Huntington's disease. Data available in other conditions document a placebo response in a varied phenomenology. We found different placebo responses according to clinical domains assessed, type of outcomes used for the same clinical domain, and modes of treatment administration, including rehabilitation and surgical interventions. Data on the nocebo response were very scarce. Although the data available are limited, RLS has the better documentation of placebo and nocebo responses. In contrast, atypical parkinsonisms are the group of movement disorders with the least knowledge. The clinical entities with a more robust placebo response are those that have the most beneficial available symptomatic treatments. © 2018 International Parkinson and Movement Disorder Society
High‐dose vitamin D: Without benefit but not without risk

It is now 100 years since deficiency of vitamin D was identified as the cause of rickets and osteomalacia (see Figure). Since then, enormous amounts of work have been undertaken elucidating the synthesis and catabolism of vitamin D, the regulation of these processes, and the mechanisms of action of vitamin D metabolites on calcium and bone metabolism. The findings of the early studies, mainly in children, that vitamin D promotes the growth and mineralisation of the skeleton have been generalised to other contexts, and vitamin D has become widely used in many conditions associated with decreases in skeletal strength, particularly in the prevention and treatment of osteoporosis. This article is protected by copyright. All rights reserved.
Role of ghrelin in pancreatic development and function

Ghrelin is a gastric peptide with anabolic functions. It acutely stimulates growth hormone (GH) secretion from the anterior pituitary glands and modulates hypothalamic circuits that control food intake and energy expenditure. Besides its central activity, ghrelin is also involved in the regulation of pancreatic development and physiology. Particularly, several studies highlighted the ability of ghrelin to sustain β‐cell viability and proliferation. Furthermore, ghrelin seems to exert inhibitory effects on pancreatic acinar and endocrine secretory functions. Due to its pleiotropic activity on energy metabolism, ghrelin has become a topic of great interest for experimental research focused on type II diabetes and obesity. The aim of this review is to illustrate the complex and not fully understood interplay between ghrelin, pancreas and glucose homeostasis.
Family physicians health-related absenteeism at the Al-Wazarat Healthcare Center

Background: In general, physicians and family physicians more specifically tend to treat themselves in an informal matter. The evidence suggests that family physicians have a tendency not to consult other physicians while they are sick and tend to self-treat. Health-related absenteeism among family physicians in primary care settings is an issue that needs to be addressed. Aim: The aim of this study is to identify the prevalence of health-related absenteeism among family physicians in Al-Wazarat Health Center and to investigate the medical causes associated with sickness absence. Methods: The study used cross-sectional design to investigate the prevalence of health-related absenteeism among family physicians in a primary care setting. Results: The study included 108 physicians from the Al-Wazarat Healthcare Center in Riyadh, KSA. On average, the physicians were absent for 2 days over the last year with 53.3% (64/108) have no health-related absence days. The most common recorded reasons for work absence are the severity of illness 75.0% (81/108) and workload 63.0% (68/108). Influenza was the most common health condition that causes absenteeism 60.2% (65/108). The attitude toward working while ill scored 2.3 ± 2.5, being responsible for affecting the patients if working while ill 8.0 ± 2.8, physicians with chronic diseases should stay away from work 3.7 ± 3.7, and the quality of healthcare service could be affected by the physician's illness 7.5 ± 2.5. Conclusions: Further investigations are needed for more understanding of the physicians' tendencies and casual approach toward working with illness. Such understanding will help to formulate better guidelines for medical practices.
How Do Actions Influence Attitudes? An Inferential Account of the Impact of Action Performance on Stimulus Evaluation

Over the past decade, an increasing number of studies have shown that the performance of specific actions (e.g., approach and avoidance) in response to a stimulus can lead to changes in how that stimulus is evaluated. In contrast to the reigning idea that these effects are mediated by the automatic formation and activation of associations in memory, we describe an inferential account that specifies the inferences underlying the effects and how these inferences are formed. We draw on predictive processing theories to explain the basic processes underlying inferential reasoning and their main characteristics. Our inferential account accommodates past findings, is supported by new findings, and leads to novel predictions as well as concrete recommendations for how action performance can be used to influence real-world behavior.
Robustness Guarantees for Bayesian Inference with Gaussian Processes

Bayesian inference and Gaussian processes are widely used in applications ranging from robotics and control to biological systems. Many of these applications are safety-critical and require a characterization of the uncertainty associated with the learning model and formal guarantees on its predictions. In this paper we define a robustness measure for Bayesian inference against input perturbations, given by the probability that, for a test point and a compact set in the input space containing the test point, the prediction of the learning model will remain δ−close for all the points in the set, for δ > 0. Such measures can be used to provide formal probabilistic guarantees for the absence of adversarial examples. By employing the theory of Gaussian processes, we derive upper bounds on the resulting robustness by utilising the Borell-TIS inequality, and propose algorithms for their computation. We evaluate our techniques on two examples, a GP regression problem and a fully-connected deep neural network, where we rely on weak convergence to GPs to study adversarial examples on the MNIST dataset.
Beyond not bad or just okay: social predictors of young adults’ wellbeing and functioning (a TRAILS study)

Abstract Background Various childhood social experiences have been reported to predict adult outcomes. However, it is unclear how different social contexts may influence each other's effects in the long run. This study examined the joint contribution of adolescent family and peer experiences to young adult wellbeing and functioning. Methods Participants came from the TRacking Adolescents’ Individual Lives Survey (TRAILS) study (n = 2230). We measured family and peer relations at ages 11 and 16 (i.e. family functioning, perceived parenting, peer status, peer relationship quality), and functioning as the combination of subjective wellbeing, physical and mental health, and socio-academic functioning at age 22. Using structural equation modelling, overall functioning was indicated by two latent variables for positive and negative functioning. Positive, negative and overall functioning at young adulthood were regressed on adolescent family experiences, peer experiences and interactions between the two. Results Family experiences during early and mid-adolescence were most predictive for later functioning; peer experiences did not independently predict functioning. Interactions between family and peer experiences showed that both protective and risk factors can have context-dependent effects, being exacerbated or overshadowed by negative experiences or buffered by positive experiences in other contexts. Overall the effect sizes were modest at best. Conclusions Adolescent family relations as well as the interplay with peer experiences predict young adult functioning. This emphasizes the importance of considering the relative effects of one context in relation to the other.