Miracle-dz/UniFAR-FTUs huggingface dataset:
Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle.

BACKGROUND Plasma-derived cell-free tumor DNA (ctDNA) constitutes a potential surrogate for tumor DNA obtained from tissue biopsies. We posit that massively parallel sequencing (MPS) analysis of ctDNA may help define the repertoire of mutations in breast cancer and monitor tumor somatic alterations during the course of targeted therapy. PATIENT AND METHODS A 66-year-old patient presented with synchronous estrogen receptor-positive/HER2-negative, highly proliferative, grade 2, mixed invasive ductal-lobular carcinoma with bone and liver metastases at diagnosis. DNA extracted from archival tumor material, plasma and peripheral blood leukocytes was subjected to targeted MPS using a platform comprising 300 cancer genes known to harbor actionable mutations. Multiple plasma samples were collected during the fourth line of treatment with an AKT inhibitor. RESULTS Average read depths of 287x were obtained from the archival primary tumor, 139x from the liver metastasis and between 200x and 900x from ctDNA samples. Sixteen somatic non-synonymous mutations were detected in the liver metastasis, of which 9 (CDKN2A, AKT1, TP53, JAK3, TSC1, NF1, CDH1, MML3 and CTNNB1) were also detected in >5% of the alleles found in the primary tumor sample. Not all mutations identified in the metastasis were reliably identified in the primary tumor (e.g. FLT4). Analysis of ctDNA, nevertheless, captured all mutations present in the primary tumor and/or liver metastasis. In the longitudinal monitoring of the patient, the mutant allele fractions identified in ctDNA samples varied over time and mirrored the pharmacodynamic response to the targeted therapy as assessed by positron emission tomography-computed tomography. CONCLUSIONS This proof-of-principle study is one of the first to demonstrate that high-depth targeted MPS of plasma-derived ctDNA constitutes a potential tool for de novo mutation identification and monitoring of somatic genetic alterations during the course of targeted therapy, and may be employed to overcome the challenges posed by intra-tumor genetic heterogeneity. REGISTERED CLINICAL TRIAL www.clinicaltrials. gov, NCT01090960.
Extracting Characteristics of the Study Subjects from Full-Text Articles

Characteristics of the subjects of biomedical research are important in determining if a publication describing the research is relevant to a search. To facilitate finding relevant publications, MEDLINE citations provide Medical Subject Headings that describe the subjects' characteristics, such as their species, gender, and age. We seek to improve the recommendation of these headings by the Medical Text Indexer (MTI) that supports manual indexing of MEDLINE. To that end, we explore the potential of the full text of the publications. Using simple recall-oriented rule-based methods we determined that adding sentences extracted from the methods sections and captions to the abstracts prior to MTI processing significantly improved recall and F1 score with only a slight drop in precision. Improvements were also achieved in directly assigning several headings extracted from the full text. These results indicate the need for further development of automated methods capable of leveraging the full text for indexing.
Results of Combined Cyclectomy/Trabeculectomy Procedure Compared with Ahmed Glaucoma Valve Implant in Neovascular Glaucoma Cases

Purpose. Cyclectomy/trabeculectomy and Ahmed glaucoma valve implant are operations suggested for refractory glaucomas. In this study, we have evaluated the outcomes that we observed with these two techniques in neovascular glaucoma patients. Material and Methods. Thirty-five eyes with neovascular glaucomas were included in this study. Ahmed Glaucoma valve (group A) was applied to ten eyes, while cyclectomy/trabeculectomy was applied to 25 eyes (group C/T). Vision, intraocular pressure and complications were evaluated at the end of the first week and after 6 and 12 months. Results. Vision preservations were 80% and 92%, and success rates in reducing intraocular pressure were 50% and 72% for Ahmed glaucoma valve and cyclectomy/trabeculectomy groups, respectively. None of the differences in complication rates was found to be statistically significant. Conclusions. In the surgical management of neovascular glaucoma, cyclectomy/trabeculectomy was shown to be an alternative to Ahmed glaucoma valve operation.
Long‐term outcome of mycophenolate mofetil rescue therapy for resistant acute allograft rejection in pediatric liver transplant recipients

Mycophenolate mofetil (MMF) has been used to rescue liver allografts with steroid‐resistant rejection (SRR). However, the long‐term outcome of these patients is not known. This study evaluates the long‐term outcome of MMF rescue therapy for SRR in pediatric liver allograft recipients. Twenty‐six children (who received 28 liver transplants), including 16 girls, were given MMF for SRR. The median age at transplant was 1.7 (range 0.4‐13.6) years. Primary immunosuppression was cyclosporine‐based in 22 and tacrolimus‐based in 6. All patients except one had been converted to tacrolimus prior to MMF, having already received a median of 2 (1‐5) courses of high‐dose intravenous methylprednisolone. The median time to MMF rescue therapy was 1.8 (0.4‐35.8) months. Twenty‐one of 28 episodes of SRR responded to MMF therapy. The median follow‐up was 8.8 (7.7‐11.5) years. In responders, there was 1 death from posttransplant lymphoproliferative disease, and no grafts were lost to chronic rejection. In the 7 nonresponders, 3 grafts were lost to chronic rejection with 2 patient deaths. Surviving children are clinically well with good liver function, and 17 remain on MMF. Three children have glomerular filtration < 80 mL/minute/1.73 m2. Side effects of MMF were seen in 12 patients; diarrhea (n = 5) and leukopenia (n = 5) being the most common. MMF was found to be effective in treating SRR in pediatric allograft recipients, with good long‐term graft function and an acceptable side‐effect profile. Liver Transpl 14:1303–1308, 2008. © 2008 AASLD.
From Double-Pancake Coils to a Layer Wound 5 T REBCO-HTS High Field Insert Coil Design

The superconducting high field facility HOMER II of the Karlsruhe Institute of Technology (KIT) provides a magnetic field of 20 T in a large bore of 185 mm using solenoid magnet sections made of NbTi and (NbX)3Sn wires. One of the major goals of the high field laboratory at KIT is to upgrade this basic magnet configuration of HOMER II to achieve a total field of 25 T. Recently, a design for a 5 T insert has been proposed using REBCO-HTS. The envisaged layout consists of two series-connected nested stacks of double pancakes. Meanwhile, the increased long-length availability of REBCO-HTS makes a 5 T insert composed of layer wound solenoid sections an attractive option. In this paper, a design for such a layer wound 5 T insert for the HOMER II upgrade is presented. Furthermore, the manufacture and test of a prototype layer wound HTS section made of a 170 m length of RE BCO coated conductor tape is reported.
Selective induction of apoptosis of NB4 cells from G2+M phase by sodium arsenite at lower doses

Abstract: Apoptosis of NB4 cells induced by sodium arsenite and arsenate was studied using flow cytometry and DNA gel electrophoresis in order to investigate their effects on cell cycle and determine the relationship between apoptosis and cell cycle. In this study, we found that: 1) at low doses, sodium arsenite selectively induced apoptosis of NB4 cells in G2+M phase of cell cycle after its being arrested in G2 phase. With increment of the cells blocked in G2 phase, dUTP‐specifically labeling cells in G2+M phase increased without concomitant increment of dUTP‐labeling cells in other two phases of cell cycle; 2) at high doses, extensive apoptosis was induced in NB4 cells from all phases of cell cycle without cell cycle preference and cell cycle blockade; 3) sodium arsenite‐induced apoptosis of NB4 cells occurred in the presence of bcl‐2 expression as the unapoptotic cells; 4) sodium arsenite with As3+ induced apoptosis of NB4 cells more strongly than sodium arsenate with As5+ did although both of them affected NB4 cells in the same pattern. These results not only suggested that both arsenite and arsenate induced apoptosis of NB4 cells through 2 different mechanisms ‐ at low doses, arsenical might directly induce apoptosis through regulation of cell cycle checkpoint, while at high doses they might directly induce it, but also indicated that bcl‐2 might not play an important role in arsenite or arsenate‐induced apoptosis of NB4 cells, whereas chemical valence of As in a compound might be related to efficiency in arsenical induction of apoptosis.
Supporting Spoken Assistant Systems with a Graphical User Interface that Signals Incremental Understanding and Prediction State

Arguably, spoken dialogue systems are most often used not in hands/eyes-busy situations, but rather in settings where a graphical display is also available, such as a mobile phone. We explore the use of a graphical output modality for signalling incremental understanding and prediction state of the dialogue system. By visual-ising the current dialogue state and possible continuations of it as a simple tree, and allowing interaction with that visualisation (e.g., for conﬁrmations or corrections), the system provides both feedback on past user actions and guidance on possible future ones, and it can span the continuum from slot ﬁlling to full prediction of user intent (such as GoogleNow). We evaluate our system with real users and report that they found the system intuitive and easy to use, and that incremental and adaptive settings enable users to accomplish more tasks.
Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen

Background ER-positive (ER+ ) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only. Methods Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan–Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance. Results All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8.5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%–100%). Conclusions Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.
Identifying factors influencing the customers purchase behaviour due to location-based promotions

Using location-based promotions, marketers have the opportunity to present information to consumers which is specific to their current location. In this paper, which uses a field study and a follow-up in-app-survey, the authors identify factors which influence mobile location-based advertising and more specifically, which factors influence the customer purchase as a result of mobile location-based advertising via a mobile application (app). The study found that the usage frequency of and the satisfaction with the specific location-based advertising app used are factors which significantly influence purchase behaviour when using mobile location-based advertising.
Secretome Signature Identifies ADAM17 as Novel Target for Radiosensitization of Non–Small Cell Lung Cancer

Purpose: Ionizing radiation (IR) induces intracellular signaling processes as part of a treatment-induced stress response. Here we investigate IR-induced ADAM17 activation and the role of ADAM17-shed factors for radiation resistance in non–small cell lung cancer. Experimental Design: Large-scale secretome profiling was performed using antibody arrays. Secretion kinetics of ADAM17 substrates was determined using ELISA across multiple in vitro and in vivo models of non–small cell lung cancer. Clonogenic survival and tumor xenograft assays were performed to determine radiosensitization by ADAM17 inhibition. Results: On the basis of a large-scale secretome screening, we investigated secretion of auto- or paracrine factors in non–small cell lung cancer in response to irradiation and discovered the ADAM17 network as a crucial mediator of resistance to IR. Irradiation induced a dose-dependent increase of furin-mediated cleavage of the ADAM17 proform to active ADAM17, which resulted in enhanced ADAM17 activity in vitro and in vivo. Genetic or pharmacologic targeting of ADAM17 suppressed IR-induced shedding of secreted factors, downregulated ErbB signaling in otherwise cetuximab-resistant target cells, and enhanced IR-induced cytotoxicity. The combined treatment modality of IR with the ADAM17 inhibitor TMI-005 resulted in a supra-additive antitumor response in vivo demonstrating the potential of ADAM17 targeting in combination with radiotherapy. Conclusions: Radiotherapy activates ADAM17 in non–small cell lung cancer, which results in shedding of multiple survival factors, growth factor pathway activation, and IR-induced treatment resistance. We provide a sound rationale for repositioning ADAM17 inhibitors as short-term adjuvants to improve the radiotherapy outcome of non–small cell lung cancer. Clin Cancer Res; 22(17); 4428–39. ©2016 AACR.
A statistical analysis of the galaxy populations of distant luminous X-ray clusters

We present a deep, multicolour (UBI) CCD survey using the Palomar 5-m telescope of a sample of high X-ray luminosity, distant clusters selected from the ROSAT All-Sky Survey. The 10 clusters lie in the redshift range z= 0.22–0.28, an era in which evolutionary effects have been reported in the properties of cluster galaxy populations.Our clusters thus provide a well-defined sample of the most massive systems at these redshifts with which to quantify the extent and variability of these evolutionary effects. The relatively low redshifts of these clusters also means that simple connections can be made between the galaxy populations of these clusters and their immediate descendents, local rich clusters. Moreover, by concentrating on a narrow redshift range, we can take advantage of the homogeneity of our cluster sample to combine the galaxy catalogues from all the clusters to analyse statistically the bulk properties of their populations. We present an analysis of the cluster galaxy populations using our multicolour data to probe the distribution, luminosities and star formation histories of galaxies in these regions. Our aim is to chart the characteristics of the galaxy populations of massive intermediate redshift clusters and to combine these into a wider scheme for galaxy evolution in high-density environments. The core regions of clusters in our sample contain only a small proportion of star-forming galaxies, and they therefore do not exhibit a classical “Butcher–Oemler” effect. Focusing on the redder cluster galaxies, we find that their integrated luminosity is well correlated with the X-ray temperatures of the clusters, and hence with cluster mass. Furthermore, the typical rest frame UV–optical colours of the luminous elliptical sequences in the clusters exhibit a remarkably small cluster-to-cluster scatter, ≲2 per cent, indicating that these galaxies are highly homogeneous between cluster environments. However, at fainter magnitudes we observe a marked increase in the range of mid-UV colours of galaxies possessing strong 4000-A breaks, as determined from photometry in ∼7.5 h-1 kpc diameter apertures. In the light of the apparent decline in the population of S0 galaxies seen in distant z≳0.4, clusters, and in view of the luminosities and colours of this population, we propose that they may be the progenitors of the dominant S0 population of rich local clusters, caught in the final stage before they become completely quiescent. Further studies of this population will prove a necessary link with which to connect the evolution observed in cluster populations at high redshift with the nature of the final remnants locally. Observations in the rest frame UV will be important in these studies owing to the relative ease of detecting the signature of previous activity in this spectral region.
Ictal cerebral blood flow in seizures originating in the posterolateral cortex.

UNLABELLED In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.
Morphology and Ciliary Motion of Mucosa in the Eustachian Tube of Neonatal and Adult Gerbils

The Eustachian tube is a small canal that connects the tympanic cavity with the nasal part of the pharynx. The epithelial lining of the Eustachian tube contains a ciliated columnar epithelium at the tympanic cavity and a pseudostratified, ciliated columnar epithelium with goblet cells near the pharynx. The tube serves to equalize air pressure across the eardrum and drains mucus away from the middle ear into the nasopharynx. Blockage of the Eustachian tube is the most common cause of all forms of otitis media, which is common in children. In the present study, we examined the epithelial lining of the Eustachian tube in neonatal and adult gerbils, with a focus on the morphological and functional development of ciliated cells in the mucosa. The length of the tube is ∼8.8 mm in adult gerbils. Scanning electron microscopy showed that the mucosal member near the pharyngeal side contains a higher density of ciliated cells and goblet cells than that near the tympanic side. The cilia beat frequency is 11 Hz. During development, the length of the Eustachian tube increased significantly between postnatal day 1 (P1) and P18. Scanning electron microscopy showed that the mucosa contained a high density of ciliated cells with a few goblet cells at P1. The density of ciliated cells decreased while the density of goblet cells increased during development. At P18, the mucosa appeared to be adult-like. Interestingly, the ciliary beat frequency measured from ciliated cells at P1 was not statistically different from that measured from adult animals. Our study suggests that the Eustachian tube undergoes significant anatomical and histological changes between P1 and P18. The tube is morphologically and functionally mature at P18, when the auditory function (sensitivity and frequency selectivity) is mature in this species.
Terrain variables used for predictive mapping of vegetation communities in southern California

Distributions of plant species on the landscape are related to soil-moisture balance in the semiarid Mediterranean-type climate of southern California. Moisture supply, subsurface soil moisture, soil properties related to moisture-holding capacity, and soil-Soisture demand (evapotranspiration) have been shown to be related to topographic variables. Those variables include elevation, aspect, slope, curvature, billslope position and drainage basin position, and more complex topographically derived indices such as potential solar insolation and soil-water balance (Chapters I, 3, and 4 and references therein). In this chapter we discuss the use of terrain variables for predictive vegetation mapping (reviewed by Franklin 1995) of chaparral and riparian vegetation in southern California. Before describing our case studies, we review the following issues related to ecological applications of terrain models:
Improving the Accuracy of High Performance BLAS Implementations Using Adaptive Blocked Algorithms

Matrix multiply is ubiquitous in scientific computing. Considerable effort has been spent on improving its performance. Once methods that make efficient use of the processor have been exhausted, methods that use less operations than the canonical matrix multiply must be explored. Combining the two methods yields a hybrid matrix multiply algorithm. Hybrid matrix multiply algorithms tend to be less accurate than the canonical matrix multiply implementation, leaving room for improvement. There are well-known techniques for improving accuracy, but they tend to be slow and it is not immediately obvious how best to apply them to hybrid algorithms without lowering performance. Previous attempts have focused on the bottom of the hybrid matrix multiply algorithm, modifying the high-performance matrix multiply implementation. In contrast, the top-down approach presented here does not require the modification of the high-performance matrix multiply implementation at the bottom, nor does it require modification of the fast asymptotic matrix multiply algorithm at the top. The three-level hybrid algorithm presented here not only has up to 10% better performance than the fastest high-performance matrix multiply, but is also more accurate.