Miracle-dz/UniFAR-FTUs huggingface dataset:
Developments in the management of advanced soft-tissue sarcoma – olaratumab in context

Lartruvo® (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFRα). The antitumor activity of olaratumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in cancer cell lines, including glioblastoma and leiomyosarcoma cells. It represents the first-in-class antibody to be approved by regulatory authorities for the treatment of advanced soft-tissue sarcomas (STSs) in combination with doxorubicin, based on the results of the Phase Ib/II trial by Tap et al. The median progression-free survival (PFS), which was the primary end point of the study, was improved for patients treated with olaratumab plus doxorubicin compared to those treated with doxorubicin monotherapy (6.6 vs 4.1 months, respectively; HR 0.672, 95% CI 0.442–1.021, p=0.0615). Moreover, final analysis of overall survival (OS) showed a median OS of 26.5 months with olaratumab plus doxorubicin vs 14.7 months with doxorubicin, with a gain of 11.8 months (HR 0.46, 95% CI 0.30–0.71, p=0.0003). In October 2016, olaratumab was admitted in the Accelerated Approval Program by the US Food and Drug Administration (FDA) for use in combination with doxorubicin for the treatment of adult patients with STSs. In November 2016, the European Medicines Agency (EMA) granted conditional approval for olaratumab in the same indication under its Accelerated Assessment Program. A double-blind, placebo-controlled, randomized Phase III study (ANNOUNCE trial, NCT02451943) is being performed in order to confirm the survival advantage of olaratumab and to provide definitive drug confirmation by regulators. The study is ongoing, but enrollment is closed. The purpose of this review was to evaluate the rationale of olaratumab in the treatment of advanced STSs and its emerging role in clinical practice.
Assessment of body composition of poultry by nuclear magnetic resonance imaging and spectroscopy.

Nuclear magnetic resonance (NMR) imaging and spectroscopy were used to assess body composition of the chicken and turkey poult. The NMR imaging was performed using a clinical, whole-body imaging system operating at 1.5 tesla (T; 63 MHz). Three-dimensional reconstruction of cross-sectional images made along the transaxial plane was used to estimate mass of the Pectoralis muscle of chickens ranging in weight from 140 to 2,760 g. Results indicate that NMR imaging can be used to determine size of the Pectoralis muscle (R2 = .99) in the bird, thus permitting repetitive measurements during the growth and development of the bird. The NMR spectroscopy was performed using an imaging spectrometer operating at 4.7 T (200 MHz). Integral areas of the water and lipid proton peaks of the spectra were compared with the water and lipid content of the whole body as determined by chemical analysis. Regression analysis of measurements made on turkey poults, ranging in weight from 115 to 630 g (n = 6), resulted in R2 values of . 94 for NMR water proton peak area and total body water, . 93 for NMR lipid proton peak area and total body lipid, and . 96 for NMR water proton peak area and total body protein. From NMR spectroscopy of chickens weighing 528 +/- 18 g (n = 6), the relative area of the lipid peak correlated with whole-body lipid (R2 = .97). Thus, whole-body spectroscopy of smaller birds can be used to measure total body water, protein, and lipid content.
Primary and recurrent ovarian high-grade serous carcinomas display similar microRNA expression patterns relative to those of normal ovarian tissue

Most patients with epithelial ovarian cancer eventually die due to recurrence. However, little is known about the microRNA (miRNA) expression pattern and its involvement in recurrent ovarian cancer. We analyzed miRNA expression profiles related to the recurrence of advanced ovarian high-grade serous carcinoma (HGSC) using miRNA microarrays. Between May 2006 and December 2012, 37 ovarian HGSC patients underwent secondary cyto-debulking surgery at recurrence. Among them, only 8 pairs of primary and recurrent tumor samples were deemed to be adequate for analysis. The expression profiles of primary ovarian HGSC compared with normal ovarian tissue were significantly consistent with those of recurrent ovarian HGSC compared with normal ovarian tissue (correlation coefficient = 0.81, P = 0.0078). Among 31 miRNAs that increased by more than 4-fold in primary tumors compared with normal ovarian tissue, 27 were also significantly increased in recurrent tumor samples. Likewise, among 35 miRNAs that decreased by more than 4-fold in primary tumors compared with normal ovarian tissue, 34 were also significantly decreased in recurrent tumor samples. We identified 60 miRNAs that were significantly increased in recurrent serous ovarian carcinoma compared with primary tumor tissue, including miR-630, miR-370, and miR-575. Additionally, 52 miRNAs were significantly decreased in recurrent samples, including miR-509-3p, miR-514a-3p, and miR-506-3p. Our results demonstrate that primary and recurrent ovarian HGSC displayed similar miRNA expression patterns. Nevertheless, altered miRNA expression could be implicated in the recurrence of ovarian HGSC, and further study is needed to validate these data in independent cases using a homogeneous methodology.
When Good Components Go Bad: Formally Secure Compilation Despite Dynamic Compromise

We propose a new formal criterion for evaluating secure compilation schemes for unsafe languages, expressing end-to-end security guarantees for software components that may become compromised after encountering undefined behavior---for example, by accessing an array out of bounds. Our criterion is the first to model dynamic compromise in a system of mutually distrustful components with clearly specified privileges. It articulates how each component should be protected from all the others---in particular, from components that have encountered undefined behavior and become compromised. Each component receives secure compilation guarantees---in particular, its internal invariants are protected from compromised components---up to the point when this component itself becomes compromised, after which we assume an attacker can take complete control and use this component's privileges to attack other components. More precisely, a secure compilation chain must ensure that a dynamically compromised component cannot break the safety properties of the system at the target level any more than an arbitrary attacker-controlled component (with the same interface and privileges, but without undefined behaviors) already could at the source level. To illustrate the model, we construct a secure compilation chain for a small unsafe language with buffers, procedures, and components, targeting a simple abstract machine with built-in compartmentalization. We give a careful proof (mostly machine-checked in Coq) that this compiler satisfies our secure compilation criterion. Finally, we show that the protection guarantees offered by the compartmentalized abstract machine can be achieved at the machine-code level using either software fault isolation or a tag-based reference monitor.
Sustainability and public health nutrition at school: assessing the integration of healthy and environmentally sustainable food initiatives in Vancouver schools

Abstract Objective To describe the development and application of the School Food Environment Assessment Tools and a novel scoring system to assess the integration of healthy and environmentally sustainable food initiatives in elementary and secondary schools. Design The cross-sectional study included direct observations of physical food environments and interviews with key school personnel regarding food-related programmes and policies. A five-point scoring system was then developed to assess actions across six domains: (i) food gardens; (ii) composting systems; (iii) food preparation activities; (iv) food-related teaching and learning activities; and availability of (v) healthy food; and (vi) environmentally sustainable food. Setting Vancouver, Canada. Subjects A purposive sample of public schools (n 33) from all six sectors of the Vancouver Board of Education. Results Schools scored highest in the areas of food garden and compost system development and use. Regular integration of food-related teaching and learning activities and hands-on food preparation experiences were also commonly reported. Most schools demonstrated rudimentary efforts to make healthy and environmentally sustainable food choices available, but in general scored lowest on these two domains. Moreover, no schools reported widespread initiatives fully supporting availability or integration of healthy or environmentally sustainable foods across campus. Conclusions More work is needed in all areas to fully integrate programmes and policies that support healthy, environmentally sustainable food systems in Vancouver schools. The assessment tools and proposed indicators offer a practical approach for researchers, policy makers and school stakeholders to assess school food system environments, identify priority areas for intervention and track relevant changes over time.
Modeling of Inner Interlayer Prediction in Thick Oil Layer——with Velasquez Oilfield as an Example

The inner interlayers are the main causes for forming multi-layer reservoirs with strong heterogeneity,which control the remaining oil distribution.Velasquez oilfield is located in the central part of Magdalenda basin in Columbia,and the paleogene group G sandstone reservoirs are of braided channel deposition.Muddy interlayer and interlayer of physical property are developed in the G reservoirs in Velasquez oilfield.Muddy interlayer consists mainly of flood argillaceous sediments,with the porosity less than 5%,and the permeability less than 1×10-3μm2. The porosity of physical interlayer is less than 11.3%,and the permeability is less than 23.3×10-3μm2. Two models for interlayers are built in order to identify interlayers in the whole area and to carry out lateral correlation.According to their planar distributions,the interlayers in the study area are divided into the steady,sub-steady and stochastic types,and then their interwell distributions are predicted by using the methods of interwell correlation,lower limit of physical property control and conditional simulation,respectively,in order to build the interlayer 3D distribution model and provide foundations for predicting remaining oil distribution.The method enjoys the necessary accuracy for the high water-cut reservoir interlining.
The clinical application of teaching people about pain

ABSTRACT Teaching people about the neurobiology and neurophysiology of their pain experience has a therapeutic effect and has been referred to as pain neuroscience education (PNE). Various high-quality randomized controlled trials and systematic reviews have shown increasing efficacy of PNE decreasing pain, disability, pain catastrophization, movement restrictions, and healthcare utilization. Research studies, however, by virtue of their design, are very controlled environments and, therefore, in contrast to the ever-increasing evidence for PNE, little is known about the clinical application of this emerging therapy. In contrast, case studies, case series, and expert opinion and perspectives by authorities in the world of pain science provide clinicians with a glimpse into potential “real” clinical application of PNE in the face of the ever-increasing chronic pain epidemic. By taking the material from the randomized controlled trials, systematic reviews, case series, case studies, and expert opinion, this article aims to provide a proposed layout of the clinical application of PNE. The article systematically discusses key elements of PNE including examination, educational content, and delivery methods, merging of PNE with movement, goal setting, and progression. This perspectives article concludes with a call for research into the clinical application of PNE.
Automatic Pavement Crack Detection Based on Structured Prediction with the Convolutional Neural Network

Automated pavement crack detection is a challenging task that has been researched for decades due to the complicated pavement conditions in real world. In this paper, a supervised method based on deep learning is proposed, which has the capability of dealing with different pavement conditions. Specifically, a convolutional neural network (CNN) is used to learn the structure of the cracks from raw images, without any preprocessing. Small patches are extracted from crack images as inputs to generate a large training database, a CNN is trained and crack detection is modeled as a multi-label classification problem. Typically, crack pixels are much fewer than non-crack pixels. To deal with the problem with severely imbalanced data, a strategy with modifying the ratio of positive to negative samples is proposed. The method is tested on two public databases and compared with five existing methods. Experimental results show that it outperforms the other methods.
In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells.

BACKGROUND Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms. METHODS We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients. RESULTS In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts. CONCLUSIONS Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.
Controlled egg weight loss during incubation of turkey eggs.

Weight loss (12%) of turkey eggs in a commercial incubator by a weekly adjustment of relative humidity (RH) was compared in four independent trials with the industry standard of maintaining 58% RH. Trials 1 and 2 were conducted with eggs from one flock of recycled hens during their 14th and 20th week of lay, respectively. Trials 3 and 4 were conducted with first cycle hens during their 3rd and 10th week of lay, respectively. Hatch of eggs was significantly better when eggs were incubated to lose an optimum amount of weight. Hatch of fertile eggs was significantly improved (P less than .05) in all except Trial 2. Hatchability was best when loss of egg weight was not greater than 11.5% at 25 days of incubation.
Socioeconomic inequalities in dental caries among 5-year-olds in four Chinese provinces.

OBJECTIVE To explore socioeconomic inequalities in dental caries among 5-year-olds in four Chinese provinces. METHODS This study used data from 1,732 children living in Guangxi, Hubei, Jilin and Shanxi who participated in the Third National Oral Health Survey in 2005. Questionnaires were completed by parents to collect information on family socioeconomic position (parental education and household income) and children's dental behaviours (toothbrushing frequency, sugar intake frequency and last dental visit). Children were clinically examined for dental caries, which was reported using the dmft index. Socioeconomic inequalities in children's caries experience were assessed in negative binomial regression models. RESULTS There were significant gradients in children's dmft by household income. Children's dmft increased from 2.63 in the highest income group to 4.70 in the lowest income group. However, parental education was not significantly related to childhood dental caries. CONCLUSION Clear social gradients in caries experience of deciduous teeth were found by household income but not parental education.
Sex, Sleep Deprivation, and the Anxious Brain

Abstract Insufficient sleep is a known trigger of anxiety. Nevertheless, not everyone experiences these effects to the same extent. One determining factor is sex, wherein women experience a greater anxiogenic impact in response to sleep loss than men. However, the underlying brain mechanism(s) governing this sleep-loss-induced anxiety increase, including the markedly different reaction in women and men, is unclear. Here, we tested the hypothesis that structural brain morphology in a discrete network of emotion-relevant regions represents one such explanatory factor. Healthy participants were assessed across sleep-rested and sleep-deprived conditions, with brain structure quantified using gray matter volume measures. Sleep loss triggered greater levels of anxiety in women compared with men. Reduced gray matter volume in the anterior insula and lateral orbitofrontal cortex predicted the anxiogenic impact of sleep loss in women, yet predicted resilience in men, and did so with high discrimination accuracy. In contrast, gray matter volume in ventromedial prefrontal cortex predicted the anxiogenic impact of sleep loss in both men and women. Structural human brain morphology therefore appears to represent one mechanistic pathway (and possible biomarker) determining anxiety vulnerability to sleep loss—a discovery that may help explain the higher prevalence of sleep disruption and anxiety in women.
ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated suppression of liver tumor growth in vivo. Furthermore, immunohistochemical staining demonstrated the inverse correlation of ZHX2 and MDR1 expression in HCC tissues. Luciferase report assay showed that ZHX2 repressed the MDR1 promoter activity, while knockdown of NF-YA or mutating the NF-Y binding site eliminated this ZHX2-mediated repression of MDR1 transcription. Co-IP and ChIP assay further suggested that ZHX2 interacted with NF-YA and reduced NF-Y binding to the MDR1 promoter. Taken together, we clarify that ZHX2 represses NF-Y-mediated activation of MDR1 transcription and, in doing so, enhances the effects of chemotherapeutics in HCC cells both in vitro and in vivo.
Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil.

OBJECTIVE The objective of this study was to evaluate the presence of vitamin B12 deficiency and the factors associated with serum vitamin B12 levels in a sample of metformin-treated Brazilian diabetic patients. METHOD Cross-sectional study. RESULTS 144 patients were included. Serum vitamin B12 levels were low (< 125 pmol/L) in 10 patients (6.9%) and possibly low (125 - 250 pmol/L) in 53 patients (36.8%). Serum vitamin B12 levels were negatively associated with age (B = -3.17; β= -0.171; p = 0.037) and duration of metformin use (B= -33.36; β= -0.161; p = 0.048), and positively associated with the estimated intake of vitamin B12 (B= 67.96; β= 0.249; p = 0.002). CONCLUSION The present findings suggest a high prevalence of vitamin B12 deficiency in metformin-treated diabetic patients. Older patients, patients in long term treatment with metformin and low vitamin B12 intake are probably more prone to this deficiency.
Assessing shortfalls and complementary conservation areas for national plant biodiversity in South Korea

Protected areas (PAs) are often considered the most important biodiversity conservation areas in national plans, but PAs often do not represent national-scale biodiversity. We evaluate the current conservation status of plant biodiversity within current existing PAs, and identify potential additional PAs for South Korea. We modeled species ranges for 2,297 plant species using Multivariate Adaptive Regression Splines and compared the level of mean range representation in South Korea’s existing PAs, which comprise 5.7% of the country’s mainland area, with an equal-area alternative PA strategy selected with the reserve algorithm Marxan. We also used Marxan to model two additional conservation scenarios that add lands to approach the Aichi Biodiversity Target objectives (17% of the country). Existing PAs in South Korea contain an average of 6.3% of each plant species’ range, compared to 5.9% in the modeled equal-area alternative. However, existing PAs primarily represent a high percentage of the ranges for high-elevation and small range size species. The additional PAs scenario that adds lands to the existing PAs covers 14,587.55 km2, and would improve overall plant range representation to a mean of 16.8% of every species’ range. The other additional PAs scenario, which selects new PAs from all lands and covers 13,197.35 km2, would improve overall plant range representation to a mean of 13.5%. Even though the additional PAs that includes existing PAs represents higher percentages of species’ ranges, it is missing many biodiversity hotspots in non-mountainous areas and the additional PAs without locking in the existing PAs represent almost all species’ ranges evenly, including low-elevation ones with larger ranges. Some priority conservation areas we identified are expansions of, or near, existing PAs, especially in northeastern and southern South Korea. However, lowland coastal areas and areas surrounding the capital city, Seoul, are also critical for biodiversity conservation in South Korea.
Not-So-CLEVR: Visual Relations Strain Feedforward Neural Networks

The robust and efficient recognition of visual relations in images is a hallmark of biological vision. Here, we argue that, despite recent progress in visual recognition, modern machine vision algorithms are severely limited in their ability to learn visual relations. Through controlled experiments, we demonstrate that visual-relation problems strain convolutional neural networks (CNNs). The networks eventually break altogether when rote memorization becomes impossible such as when the intra-class variability exceeds their capacity. We further show that another type of feedforward network, called a relational network (RN), which was shown to successfully solve seemingly difficult visual question answering (VQA) problems on the CLEVR datasets, suffers similar limitations. Motivated by the comparable success of biological vision, we argue that feedback mechanisms including working memory and attention are the key computational components underlying abstract visual reasoning.