Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of inter-observer delineation variability on radiomics stability in different tumor sites

Abstract Background: Radiomics is a promising methodology for quantitative analysis and description of radiological images using advanced mathematics and statistics. Tumor delineation, which is still often done manually, is an essential step in radiomics, however, inter-observer variability is a well-known uncertainty in radiation oncology. This study investigated the impact of inter-observer variability (IOV) in manual tumor delineation on the reliability of radiomic features (RF). Methods: Three different tumor types (head and neck squamous cell carcinoma (HNSCC), malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC)) were included. For each site, eleven individual tumors were contoured on CT scans by three experienced radiation oncologists. Dice coefficients (DC) were calculated for quantification of delineation variability. RF were calculated with an in-house developed software implementation, which comprises 1404 features: shape (n = 18), histogram (n = 17), texture (n = 137) and wavelet (n = 1232). The IOV of RF was studied using the intraclass correlation coefficient (ICC). An ICC >0.8 indicates a good reproducibility. For the stable RF, an average linkage hierarchical clustering was performed to identify classes of uncorrelated features. Results: Median DC was high for NSCLC (0.86, range 0.57–0.90) and HNSCC (0.72, 0.21–0.89), whereas it was low for MPM (0.26, 0–0.9) indicating substantial IOV. Stability rate of RF correlated with DC and depended on tumor site, showing a high stability in NSCLC (90% of total parameters), acceptable stability in HNSCC (59% of total parameters) and low stability in MPM (36% of total parameters). Shape features showed the weakest stability across all tumor types. Hierarchical clustering revealed 14 groups of correlated and stable features for NSCLC and 6 groups for both HNSCC and MPM. Conclusion: Inter-observer delineation variability has a relevant influence on radiomics analysis and is strongly influenced by tumor type. This leads to a reduced number of suitable imaging features.
Ecto-5′-nucleotidase (CD73) is a biomarker for clear cell renal carcinoma stem-like cells

Identification of a specific biomarker for cancer stem cells (CSCs) is of potential applications in the development of effective therapeutic strategies for renal cell carcinoma (RCC). In this study, both the RCC cell line 786-O and surgically removed clear cell RCC (ccRCC) tissues were implemented to grew as spheroids in serum-free medium supplemented with mitogens. This subpopulation possessed key characteristics defining CSCs. We also identified that surgically removed ccRCC tissues were heterogenic and there was a subpopulation of cells that was highly stained with rhodamine-123. Based on membrane-proteomic analyses, CD73 was identified as a candidate biomarker. We further found that CD73high cells were highly tumorigenic. As few as 100 CD73high cells were capable of forming xenograft tumors in non obese diabetic/severe combined immunodeficiency disease mice, whereas 1 × 105 CD73low cells did not initiate tumor formation. During successive culture, the CD73high population regenerated both CD73high and CD73low cells, whereas the CD73low population remained low expression level of CD73. Furthermore, the CD73high cells were more resistant to radiation and DNA-damaging agents than the CD73low cells, and expressed a panel of ‘stemness’ genes at a higher level than the CD73low cells. These findings suggest that a high level of CD73 expression is a bona fide biomarker of ccRCC stem-like cells. Future research will aim at the elucidation of the underlying mechanisms of CD73 in RCC development and the distinct aspects of ccRCC stem-like cells from other tumor types.
Dual Supervised Learning

Many supervised learning tasks are emerged in dual forms, e.g., English-to-French translation vs. French-to-English translation, speech recognition vs. text to speech, and image classification vs. image generation. Two dual tasks have intrinsic connections with each other due to the probabilistic correlation between their models. This connection is, however, not effectively utilized today, since people usually train the models of two dual tasks separately and independently. In this work, we propose training the models of two dual tasks simultaneously, and explicitly exploiting the probabilistic correlation between them to regularize the training process. For ease of reference, we call the proposed approach \emph{dual supervised learning}. We demonstrate that dual supervised learning can improve the practical performances of both tasks, for various applications including machine translation, image processing, and sentiment analysis.
Harvesting Discriminative Meta Objects with Deep CNN Features for Scene Classification

Recent work on scene classification still makes use of generic CNN features in a rudimentary manner. In this paper, we present a novel pipeline built upon deep CNN features to harvest discriminative visual objects and parts for scene classification. We first use a region proposal technique to generate a set of high-quality patches potentially containing objects, and apply a pre-trained CNN to extract generic deep features from these patches. Then we perform both unsupervised and weakly supervised learning to screen these patches and discover discriminative ones representing category-specific objects and parts. We further apply discriminative clustering enhanced with local CNN fine-tuning to aggregate similar objects and parts into groups, called meta objects. A scene image representation is constructed by pooling the feature response maps of all the learned meta objects at multiple spatial scales. We have confirmed that the scene image representation obtained using this new pipeline is capable of delivering state-of-the-art performance on two popular scene benchmark datasets, MIT Indoor 67 [22] and Sun397 [31].
Evaluation of microleakage in hybrid composite restoration with different intermediate layers and curing cycles

Objective: To evaluate the impact of bulk or incremental curing of hybrid composite resin with different intermediate layers on interfacial microleakage. Materials and Methods: The recently extracted, sixty noncarious human mandibular molars were selected for the study. The standardized mesio-occluso-distal cavity with the occlusal cavity of 2 mm depth, 3 mm buccolingual width and proximal box dimension of 4 mm buccolingual width and 2 mm depth was prepared on all experimental teeth. The samples were divided into six groups of ten each. Group I was without an intermediate layer. Group II and III had 1 mm flowable composite liner, with incremental and bulk curing cycle, respectively. The Group IV, V, and VI had a self-cure composite liner with incremental and bulk curing. The teeth subjected to thermocycling and kept in 0.5% basic fuchsine dye for 24 h. The teeth were sectioned and observed under a stereomicroscope to grade them according to the extent of microleakage. The obtained data were statistically analyzed with Kruskal–Wallis and post hoc comparison test to understand the difference between the groups. Results: The Group II with flowable composite along incremental curing showed the least microleakage at both enamel (0.30) and cementum surface (0.50). The groups with self-cure composite liner were less effective than flowable composite. The microleakage at the enamel interface was less compared cementum interface across the groups. The groups with bulk curing were more prone to microleakage than incremental curing cycle. Conclusions: Within the limitation of the study, it was concluded that intermediate flowable composite with incremental curing was better suited to reduce microleakage.
Reactive Oxygen Species and Nuclear Factor Erythroid 2-Related Factor 2 Activation in Diabetic Nephropathy: A Hidden Target

Hyperglycemia, oxidative stress and renin-angiotensin system (RAS) dysfunction have been implicated in diabetic nephropathy (DN) progression, but the underlying molecular mechanisms are far from being fully understood. In addition to the systemic RAS, the existence of a local intrarenal RAS in renal proximal tubular cells has been recognized. Angiotensinogen is the sole precursor of all angiotensins (Ang). Intrarenal reactive oxygen species (ROS) generation, Ang II level and RAS gene expression are up-regulated in diabetes, indicating that intrarenal ROS and RAS activation play an important role in DN. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is one of the major protective processes that occurs in response to intracellular oxidative stress. Nrf2 stimulates an array of antioxidant enzymes that convert excessive ROS to less reactive or less damaging forms. Recent studies have, however, revealed that Nrf2 activation might have other undesirable effects in diabetic animals and in diabetic patients with chronic kidney disease. This mini-review summarizes current knowledge of the relationship between ROS, Nrf2 and intra renal RAS activation in DN progression as well as possible novel target(s) for DN treatment.
Self-Compassion Online: A Pilot Study of an Internet-Based Self-Compassion Cultivation Program for Psychology Trainees.

OBJECTIVE The current study sought to conduct a preliminary investigation of the effectiveness and feasibility of a novel, self-guided online self-compassion training for reducing psychological distress and increasing self-compassion and happiness among psychology trainees. METHOD A 6-week online self-compassion cultivation program was developed and delivered to Australian psychology trainees (n = 37), and a pre-experimental repeated-measures design was used to collect change data on self-compassion, happiness, perceived stress, emotion regulation difficulties as well as symptoms of depression, anxiety, and stress. RESULTS Participants reported significant increases in self-compassion and happiness and significant decreases in depression, stress, and emotion regulation difficulties between pretest and posttest, with the majority of changes maintained at 3-month follow up. CONCLUSION This study provides preliminary evidence supporting the effectiveness and acceptability of online self-compassion training as a positive, integrated, and meaningful way of reducing distress and promoting self-compassion and happiness among trainee psychologists.
Bridging the Gap between Dialogue management and dialogue models

Why do few working spoken dialogue systems make use of dialogue models in their dialogue management? We find out the causes and propose a generic dialogue model. It promises to bridge the gap between practical dialogue management and (pattern-based) dialogue model through integrating interaction patterns with the underling tasks and modeling interaction patterns via utterance groups using a high level construct different from dialogue act.
Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Historically, lung cancer was long considered a poorly immunogenic malignancy. In recent years, however, immune checkpoint inhibitors have emerged as promising therapeutic agents in non-small cell lung cancer (NSCLC). To date, the best characterized and most therapeutically relevant immune checkpoints have been cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein-1 (PD-1) pathway. In early studies, PD-1/programmed cell death ligand-1 (PD-L1) inhibitors demonstrated promising antitumor activity and durable clinical responses in a subset of patients. Based on these encouraging results, multiple different PD-1/PD-L1 inhibitors have entered clinical development, and two agents (nivolumab and pembrolizumab) have gained regulatory approval in the United States for the treatment of NSCLC. In several large, randomized studies, PD-1/PD-L1 inhibitors have produced significant improvements in overall survival compared with single-agent docetaxel delivered in the second-line setting, effectively establishing a new standard of care in NSCLC. In the present report, we provide an overview of the rationale for checkpoint inhibitors in lung cancer, recent clinical trial data, and the need for predictive biomarkers. THE ONCOLOGIST 2017;22:81-88 IMPLICATIONS FOR PRACTICE: Strategies targeting negative regulators (i.e., checkpoints) of the immune system have demonstrated significant antitumor activity across a range of solid tumors. In non-small cell lung cancer (NSCLC), programmed cell death protein-1 (PD-1) pathway inhibitors have entered routine clinical use because of the results from recent randomized studies demonstrating superiority against single-agent chemotherapy in previously treated patients. The present report provides an overview of immune checkpoint inhibitors in lung cancer for the practicing clinician, focusing on the rationale for immunotherapy, recent clinical trial data, and future directions.
Regular Aerobic, Resistance, and Cross-Training Exercise Prevents Reduced Vascular Function Following a High Sugar or High Fat Mixed Meal in Young Healthy Adults

The postprandial state can negatively influence flow mediated dilation (FMD), a predictor of atherosclerosis and cardiovascular disease. This investigation was designed to determine the effect of regular aerobic and/or resistance exercise on postprandial FMD after a high sugar or high fat mixed meal. Forty-five healthy participants were recruited from one of four groups: lean sedentary (SED), runners, weight lifters, and cross-trainers. Participants were randomly crossed over to a high sugar meal (HSM) and a high fat mixed meal (HFMM; both fat and carbohydrate). Pre-and postprandial endothelial function was assessed for both meals using brachial artery FMD. Plasma lipids, insulin, glucose, hs-CRP, and SOD were also measured with both meals. Endothelium-independent dilation was determined via sublingual nitroglycerin. Brachial artery FMD was reduced in SED following the HSM (9.9 ± 0.9% at baseline, peak reduction at 60 min 6.5 ± 1.0%) and the HFMM (9.4 ± 0.9% at baseline, peak reduction at 120 min 5.9 ± 1.2%; P < 0.05 for both, Mean ± SEM). There was no change in FMD after either HSM or HFMM in runners, weight lifters, and cross-trainers. Post-prandial increases in blood glucose, insulin and triglycerides were less pronounced in the exercisers compared to SED. In addition, exercisers presented lower baseline plasma hs-CRP and higher SOD activity. Nitroglycerin responses were similar among groups. These results suggest that endothelial function is reduced in sedentary adults after a HSM or HFMM, but not in regular aerobic or resistance exercisers. This response may be due to favorable postprandial metabolic responses or lower postprandial levels of inflammation and oxidative stress. These findings may help to explain the cardioprotective effect of exercise.
The blood–brain barrier internalises Cryptococcus neoformans via the EphA2‐tyrosine kinase receptor

Cryptococcus neoformans is an opportunistic fungal pathogen that causes life‐threatening meningitis most commonly in populations with impaired immunity. Here, we resolved the transcriptome of the human brain endothelium challenged with C. neoformans to establish whether C. neoformans invades the CNS by co‐opting particular signalling pathways as a means to promote its own entry. Among the 5 major pathways targeted by C. neoformans, the EPH‐EphrinA1 (EphA2) tyrosine kinase receptor‐signalling pathway was examined further. Silencing the EphA2 receptor transcript in a human brain endothelial cell line or blocking EphA2 activity with an antibody or chemical inhibitor prevented transmigration of C. neoformans in an in vitro model of the blood–brain barrier (BBB). In contrast, treating brain endothelial cells with an EphA2 chemical agonist or an EphA2 ligand promoted greater migration of fungal cells across the BBB. C. neoformans activated the EPH‐tyrosine kinase pathway through a CD44‐dependent phosphorylation of EphA2, promoting clustering and internalisation of EphA2 receptors. Moreover, HEK293T cells expressing EphA2 revealed an association between EphA2 and C. neoformans that boosted internalisation of C. neoformans. Collectively, the results suggest that C. neoformans promotes EphA2 activity via CD44, and this in turn creates a permeable barrier that facilitates the migration of C. neoformans across the BBB.
Current insights into the innate immune system dysfunction in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder associated with abdominal pain and alterations in bowel habits. The presence of IBS greatly impairs patients’ quality of life and imposes a high economic burden on the community; thus, there is intense pressure to reveal its elusive pathogenesis. Many etiological mechanisms have been implicated, but the pathophysiology of the syndrome remains unclear. As a result, novel drug development has been slow and no pharmacological intervention is universally accepted. A growing evidence implicates the role of low-grade inflammation and innate immune system dysfunction, although contradictory results have frequently been presented. Mast cells (MC), eosinophils and other key immune cells together with their mediators seem to play an important role, at least in subgroups of IBS patients. Cytokine imbalance in the systematic circulation and in the intestinal mucosa may also characterize IBS presentation. Toll-like receptors and their emerging role in pathogen recognition have also been highlighted recently, as dysregulation has been reported to occur in patients with IBS. This review summarizes the current knowledge regarding the involvement of any immunological alteration in the development of IBS. There is substantial evidence to support innate immune system dysfunction in several IBS phenotypes, but additional studies are required to better clarify the underlying pathogenetic pathways. IBS heterogeneity could potentially be attributed to multiple causes that lead to different disease phenotypes, thus explaining the variability found between study results.
Synergistic Effect on Neurodegeneration by N-Truncated Aβ4−42 and Pyroglutamate Aβ3−42 in a Mouse Model of Alzheimer's Disease

The N-terminally truncated pyroglutamate Aβ3−42 (AβpE3−42) and Aβ4−42 peptides are known to be highly abundant in the brain of Alzheimer's disease (AD) patients. Both peptides show enhanced aggregation and neurotoxicity in comparison to full-length Aβ, suggesting that these amyloid peptides may play an important role in the pathogenesis of AD. The aim of the present work was to study the direct effect of the combination of AβpE3−42 and Aβ4−42 on ongoing AD-related neuron loss, pathology, and neurological deficits in transgenic mice. Bigenic mice were generated by crossing the established TBA42 and Tg4-42 mouse models expressing the N-truncated Aβ peptides AβpE3−42 and Aβ4−42, respectively. After generation of the bigenic mice, detailed phenotypical characterization was performed using either immunostainings to evaluate amyloid pathology or quantification of neuron numbers using design-based stereology. The elevated plus maze was used to study anxiety levels. In order to evaluate sensori-motor deficits, the inverted grid, the balance beam and the string suspension tasks were applied. We could demonstrate that co-expression of AβpE3−42 and Aβ4−42 accelerates neuron loss in the CA1 pyramidal layer of young bigenic mice as seen by reduced neuron numbers in comparison to single transgenic homozygous mice expressing either AβpE3−42 or Aβ4−42. This observation coincides with the robust intraneuronal Aβ accumulation observed in the bigenic mice. In addition, loss of anxiety and motor deficits were enhanced in an age-dependent manner. The sensori-motor deficits correlate with the abundant spinal cord pathology, as demonstrated by robust intracellular Aβ accumulation within motor neurons and extracellular Aβ deposition. Our observations demonstrate that a combination of AβpE3−42 and Aβ4−42 has a stronger effect on ongoing AD pathology than the peptides alone. Therefore, AβpE3−42 and Aβ4−42 might represent excellent potential therapeutic targets and diagnostic markers for AD.
Advancing progressive health policy to reduce NCDs amidst international commercial opposition: Tobacco standardised packaging in Australia

ABSTRACT This study examines how health advocates and the Australian government responded to international commercial pressure during the implementation of tobacco standardised packaging (SP) as a measure to reduce non-communicable diseases (NCDs). Relevant government and NGO documents, and media items were reviewed. Policymakers and health advocates (n = 19) in Australia were interviewed. In 2009, Australia’s National Health Taskforce recommended SP, which the Australian government announced in April 2010. In response, tobacco companies threatened the government with litigation in both domestic and international courts, claiming that SP would violate their investment and intellectual property rights. However, these legal threats were unsuccessful in forcing the government to withdrawal the SP proposal. Tobacco companies legally challenged SP, but as of February 2018 failed with each legal challenge. The political success of enacting and implementing SP against international commercial pressure was supported by legal preparation and support, and a whole-of-government approach. The Australian SP case illustrates how, against international commercial opposition, governments can build and maintain political and official support to enact and implement progressive public health measures to reduce NCDs.
Perceptual Thresholds and Priming in Amnesia

The widely accepted idea that perceptual priming is intact in amnesia was challenged recently by the suggestion that perceptual identification (PID) thresholds are elevated in amnesia and that this impairment could mask a priming deficit by artificially inflating priming scores. The authors examined the PID thresholds of amnesic patients across a wide range of stimulus conditions and accuracy levels. Baseline thresholds and priming effects were fully intact for all amnesic patients except in a condition using small stimuli (1.1° x 0.25° of visual angle). In that condition, only the patients with Korsakoff's syndrome were impaired. Accordingly, elevated perceptual thresholds are not a necessary consequence of amnesia, and normal priming in amnesia is not an artifact of threshold differences. The results support the conclusion that priming is independent of the brain structures important for declarative memory that are damaged in amnesia.