Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years

Importance In cancer models, warfarin inhibits AXL receptor tyrosine kinase–dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort. Objective To examine the association between warfarin use and cancer incidence. Design, Setting, and Participants This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups—warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017. Exposures Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled. Main Outcomes and Measures Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012). Results Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]). Conclusions and Relevance Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.
How People Use Social Information to Find out What to Want in the Paradigmatic Case of Inter-temporal Preferences

The weight with which a specific outcome feature contributes to preference quantifies a person’s ‘taste’ for that feature. However, far from being fixed personality characteristics, tastes are plastic. They tend to align, for example, with those of others even if such conformity is not rewarded. We hypothesised that people can be uncertain about their tastes. Personal tastes are therefore uncertain beliefs. People can thus learn about them by considering evidence, such as the preferences of relevant others, and then performing Bayesian updating. If a person’s choice variability reflects uncertainty, as in random-preference models, then a signature of Bayesian updating is that the degree of taste change should correlate with that person’s choice variability. Temporal discounting coefficients are an important example of taste–for patience. These coefficients quantify impulsivity, have good psychometric properties and can change upon observing others’ choices. We examined discounting preferences in a novel, large community study of 14–24 year olds. We assessed discounting behaviour, including decision variability, before and after participants observed another person’s choices. We found good evidence for taste uncertainty and for Bayesian taste updating. First, participants displayed decision variability which was better accounted for by a random-taste than by a response-noise model. Second, apparent taste shifts were well described by a Bayesian model taking into account taste uncertainty and the relevance of social information. Our findings have important neuroscientific, clinical and developmental significance.
Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis

Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.
Effective Protection Induced by a Monovalent DNA Vaccine against Dengue Virus (DV) Serotype 1 and a Bivalent DNA Vaccine against DV1 and DV2 in Mice

Dengue virus (DV) is the causal pathogen of dengue fever, which is one of the most rapidly spread mosquito-borne disease worldwide and has become a severe public health problem. Currently, there is no specific treatment for dengue; thus, a vaccine would be an effective countermeasure to reduce the morbidity and mortality. Although, the chimeric Yellow fever dengue tetravalent vaccine has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate pVAX1-D1ME expressing the prME protein of DV1 was inoculated in BALB/c mice via intramuscular injection or electroporation, and the immunogenicity and protection were evaluated. Compared with traditional intramuscular injection, administration with 50 μg pVAX1-D1ME via electroporation with three immunizations induced persistent humoral and cellular immune responses and effectively protected mice against lethal DV1 challenge. In addition, immunization with a bivalent vaccine consisting of pVAX1-D1ME and pVAX1-D2ME via electroporation generated a balanced IgG response and neutralizing antibodies against DV1 and DV2 and could protect mice from lethal challenge with DV1 and DV2. This study sheds new light on developing a dengue tetravalent DNA vaccine.
A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity

The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition.
Stream Nitrate Response to Different Burning Treatments in Southern Appalachian Forests

Southern Appalachian forests are undergoing considerable change due to altered disturbance regimes. For example, fire exclusion has had a major impact on the structure and function of pine-hardwood ecosystems. Recently, fire has been prescribed for a variety of applications: 1) stand-replacement in the form of a mimicked wildfire, 2) site-preparation as part of a fell-and-burn prescription, and 3) understory burning for fuels reduction and wildlife habitat improvement. Assessing watershed-scale responses to burning requires identification of key parameters indicative of changes in structure and function. In the southern Appalachians, nitrogen in the form of NO, is a key indicator of ecosystem change or response to disturbance. We compared stream NO,-N responses among stand-replacement fires (Winespring Creek and Hickory Branch), a fell-and-burn prescription (Jacobs Branch), and a wildfire in an old-growth deciduous forest (Joyce Kilmer). Nitrate-nitrogen concentration increased following two of the four fires. Concentrations following the fell-andburn prescription fire increased from CO.01 to a maximum of 0.075 mg L-r and remained elevated for 8 months. Similarly, stream NO, concentration increased approximately 2 weeks following the old-growth deciduous wildfire from 0.04 to a maximum of 0.50 mg L ’ and remained elevated for 6 weeks. There were no significant differences in NO, following one of the stand-replacement fires or between treatment and control or pnand post-burn following the other stand-replacement fire due to maintenance of an unburned riparian area. Although the old-growth deciduous wildfire was essentially an understory burn, the magnitude of stream N response suggests that unavailable recalcitrant forms of N may have been released during the wildfire, as well as a reflection of the potential inefficiency of old-growth forests at sequestering mobilized nutrients. In all cases, hydrologic losses of NO,-N were insignificant with respect to effects on water quality and site depletion of N. keywords: disturbance, ecosystems, nitrate response, old growth, North Carolina, prescribed fire, resistance, riparian zone, southern Appalachia, stream. Ciration: Clinton, B.D. , J.M. Vose, J.D. Knoepp, and K.J. Elliott. 2003. Stream nitrate response to different burning treatments in southern Appalachian forests. Pages 174-181 in K.E. M. Galley, R.C. Klinger, and N.G Sugihara (eds.). Proceedings of Fire Conference 2000: The First National Congress on Fire Ecology, Prevention, and Management. Miscellaneous Publication No. 13, Tall Timbers Research Station, Tallahassee, FL
Longitudinal Trend in Lipid Profile of Incident Peritoneal Dialysis Patients is Not Influenced by the Use of Biocompatible Solutions

♦ Background: The longitudinal trends of lipid parameters and the impact of biocompatible peritoneal dialysis (PD) solutions on these levels remain to be fully defined. The present study aimed to a) evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters, and b) explore the capacity of lipid parameters (total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular events (CVE) and mortality in PD patients. ♦ Methods: The study included 175 incident participants from the balANZ trial with at least 1 stored serum sample. A composite CVE score was used as a primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe the trend of lipid parameters over time and its ability to predict composite CVE, respectively. ♦ Results: Small but statistically significant increases in serum TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the serum HDL cholesterol levels (coefficient −0.004, p = 0.009) were observed with longer time on PD, whilst the type of PD solution (biocompatible vs standard) received had no significant effect on these levels. Peritoneal dialysis glucose exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL levels. Baseline lipid parameter levels were not predictive of composite CVEs or all-cause mortality. ♦ Conclusion: Serum TG, TC/HDL, and VLDL levels increased and the serum HDL levels decreased with increasing PD duration. None of the lipid parameters were significantly modified by biocompatible PD solution use over the time period studied or predictive of composite CVE or mortality.
A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition, and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects. Author summary Different insect species exhibit one of two distinct modes of determining their body segments during development: they either use a molecular oscillator to position segments sequentially, or they generate segments simultaneously through a hierarchical gene-regulatory cascade. The sequential mode is ancestral, while the simultaneous mode has been derived from it independently several times during evolution. In this paper, we present evidence which suggests that simultaneous segmentation also involves an oscillator in the posterior of the embryo of the vinegar fly, Drosophila melanogaster. This surprising result indicates that both modes of segment determination are much more similar than previously thought. Such similarity provides an important step towards explaining the frequent evolutionary transitions between sequential and simultaneous segmentation.
Heritability of Vascular Structure and Function: A Parent–Child Study

Background Understanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring. Methods and Results High‐resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow‐mediated dilation were measured in the brachial artery. Intima‐media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross‐sectional distensibility were measured, and carotid cross‐sectional compliance was measured in the carotid artery. Carotid–radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body–mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P<0.001), intima‐media thickness (h2=29±13%, P=0.014), diameter distensibility (h2=28±7%, P<0.001), cross‐sectional distensibility (h2=27±7%, P<0.001), and pulse wave velocity (h2=26±9%, P<0.001) were significantly heritable. Flow‐mediated dilation and incremental elastic modulus were not significantly heritable. Similar associations were observed in analysis restricted to siblings and complete Trios (mother, father, and child). Conclusions These data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.
Evaluation of a One-Page Report to Aid in Detecting Glaucomatous Damage.

PURPOSE We assessed the use of a customized, one-page structure + function report for aiding in detection of glaucomatous damage. METHODS Two individuals (report specialists), experienced in analyzing optical coherent tomography (OCT) and visual field (VF) results, examined a customized one-page report for 50 eyes from 50 patients who either had glaucoma or were glaucoma suspects. The report contained key features of OCT scans with VF information. All patients had 24-2 VFs with a mean deviation (MD) better than -6 dB. The report specialists classified each hemifield and eye as either glaucomatous or nonglaucomatous based upon only the customized report, either without (phase 1) or with (phase 2) 24-2 VF information included on the report. Their results were compared to the classifications made by 3 ophthalmologists (glaucoma specialists) based upon traditional measures, namely stereo photographs, 24-2 VFs, and a commercially available, OCT disc scan report. RESULTS The two report specialists agreed on all but one eye and four hemifields in phase 1, and on all eyes and all but one hemifield in phase 2. In phase 2, they judged 31 eyes abnormal. Of these 31 eyes, 30 were judged abnormal by all three glaucoma specialists and the 31st by two of the three. Without the VF information (phase 1), one report specialist classified 1, and the other 2, of these 31 "abnormal" eyes as normal. CONCLUSIONS When using the one-page report, the experienced readers showed excellent inter-rater repeatability and diagnostic ability relative to glaucoma specialists. TRANSLATIONAL RELEVANCE This condensed report may help the clinician assess glaucomatous damage.
Proteomics in biomanufacturing control: Protein dynamics of CHO‐K1 cells and conditioned media during apoptosis and necrosis

Cell viability has a critical impact on product quantity and quality during the biomanufacturing of therapeutic proteins. An advanced understanding of changes in the cellular and conditioned media proteomes upon cell stress and death is therefore needed for improved bioprocess control. Here, a high pH/low pH reversed phase data independent 2D‐LC‐MSE discovery proteomics platform was applied to study the cellular and conditioned media proteomes of CHO‐K1 apoptosis and necrosis models where cell death was induced by staurosporine exposure or aeration shear in a benchtop bioreactor, respectively. Functional classification of gene ontology terms related to molecular functions, biological processes, and cellular components revealed both cell death independent and specific features. In addition, label free quantitation using the Hi3 approach resulted in a comprehensive shortlist of 23 potential cell viability marker proteins with highest abundance and a significant increase in the conditioned media upon induction of cell death, including proteins related to cellular stress response, signal mediation, cytoskeletal organization, cell differentiation, cell interaction as well as metabolic and proteolytic enzymes which are interesting candidates for translating into targeted analysis platforms for monitoring bioprocessing response and increasing process control.
Exploring Spatial Context for 3D Semantic Segmentation of Point Clouds

Deep learning approaches have made tremendous progress in the field of semantic segmentation over the past few years. However, most current approaches operate in the 2D image space. Direct semantic segmentation of unstructured 3D point clouds is still an open research problem. The recently proposed PointNet architecture presents an interesting step ahead in that it can operate on unstructured point clouds, achieving encouraging segmentation results. However, it subdivides the input points into a grid of blocks and processes each such block individually. In this paper, we investigate the question how such an architecture can be extended to incorporate larger-scale spatial context. We build upon PointNet and propose two extensions that enlarge the receptive field over the 3D scene. We evaluate the proposed strategies on challenging indoor and outdoor datasets and show improved results in both scenarios.
Republished: Stentriever thrombectomy with distal protection device for carotid free floating thrombus: a technical case report

We report the clinical details, imaging findings and management of a 45-year-old man who presented with recurrent transient ischemic attacks due to carotid free floating thrombus. Free floating thrombus of the carotid artery is a very rare condition with a high risk of distal embolic shower. The optimal treatment options are debatable and include medical management, surgical thrombectomy and endovascular thrombectomy. We describe the use of a stentriever with filter protection in the management of carotid free floating thrombus as a novel treatment option.