Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular vesicles as drivers of epithelial‐mesenchymal transition and carcinogenic characteristics in normal prostate cells

There is increasing evidence that cancer dissemination and metastasis establishment may not only be due to the movement of tumor cells. Content of extracellular vesicles (EVs) secreted by tumor cells may also reflect the origin of these cells. Some molecules that constitute these EVs have already been used as targets for detection of specific tumors. However, to the best of our knowledge, EVs from biopsies and plasma have not yet been compared nor thoroughly investigated as triggers of malignant transformation and metastatic niche formation. To evaluate the role of EVs in the cellular microenvironment, we have treated the normal epithelial prostate cell lines, RWPE‐1 and PNT‐2, with a pool of EVs from biopsies of prostate primary tumors (bEVs), biopsies of benign prostate hyperplasia (hEVs), plasma of prostate cancer (PCa) patients (pEVs) or plasma of healthy individuals (pnEVs). Each of the four pools consisted of isolated EVs from several subjects, of which PCa patients were in different stages of cancer. Migration and proliferation profiles, cytokine release, and a panel of PCa‐associated genes' expression of epithelial‐mesenchymal transition in the cell lines were evaluated after 24 h incubation with EVs. When compared to the control groups, cells treated with the pool of EVs isolated from tumor biopsies and plasma of PCa patients showed greater migration and proliferation, significant alterations in gene expression, and high levels of IL‐8, factors that are associated with cancer development. Specifically, isolated bEVs and pEVs may induce malignant features in non‐tumor cells by activating several cellular events associated with cancer progression, suggesting that future PCa therapy may target multiple elements found in tumor‐derived EVs.
Report From the NEI/FDA Endpoints Workshop on Age-Related Macular Degeneration and Inherited Retinal Diseases

The Association for Research in Vision (ARVO), together with the Foundation Fighting Blindness (FFB), organized the National Eye Institute (NEI)–Food and Drug Administration (FDA) endpoints workshop on age-related macular degeneration (AMD) and inherited retinal diseases (IRD) on November 9, 2016. The public workshop convened basic researchers, clinicians, and regulatory authorities in an interactive forum to discuss the latest clinical findings on AMD and IRD with the goal of optimizing clinical trial design and developing trial endpoints. Specifically, the aim of the workshop was to assemble stakeholders from academic and regulatory spheres to discuss clinical data on potential primary and secondary clinical trial endpoints; patient stratification for disease monitoring, interventions, and evaluation of treatment response; and identification of future research avenues. The workshop was jointly organized by Dr. Frederick Ferris III, MD, Clinical Director at the NEI; Dr. Emily Chew, MD, Deputy Clinical Director at the NEI; Dr. Karl Csaky, MD, PhD, Managing Director and Head of Molecular Ophthalmology Laboratory at the Retina Foundation of the Southwest; Dr. Jacque L. Duncan, MD, Professor of Clinical Ophthalmology at the University of California, San Francisco; and Janet K. Cheetham, PharmD, from the FFB. The workshop format was a series of presentations followed by panel discussions, in which FDA representatives offered regulatory perspectives on potential endpoints for clinical trial design. The following key topics were discussed.
Cross-sectional analysis of the prevalence and predictors of statin utilisation in Ireland with a focus on primary prevention of cardiovascular disease

Objective To describe the prevalence of statin utilisation by people aged over 50 years in Ireland and the factors associated with the likelihood of using a statin, focusing particularly on those using statins for primary prevention of cardiovascular disease (CVD). Methods This is a cross-sectional analysis of cardiovascular risk and sociodemographic factors associated with statin utilisation from wave 1 of The Irish Longitudinal Study on Ageing. A hierarchy of indications for statin utilisation, consisting of eight mutually exclusive levels of CVD-related diagnoses, was created. Participants were assigned one level of indication. The prevalence of statin utilisation was calculated. The likelihood that an individual was using a statin was estimated using a multivariable logistic regression model, controlling for cardiovascular risk and sociodemographic factors. Results In this nationally representative sample (n=5618) of community-dwelling participants aged 50 years and over, 1715 (30.5%) were taking statins. Of these, 65.0% (57.3% of men and 72.7% of women) were doing so for the primary prevention of CVD. Thus, almost two-thirds of those taking statins did so for primary prevention and there was a notable difference between women and men in this regard. We also found that statin utilisation was highest among those with a prior history of CVD and was significantly associated with age (compared with the base category 50–64 years; 65–74 years OR 1.38 (95% CI 1.16 to 1.65); 75+ OR 1.33 (95% CI 1.04 to 1.69)), living with a spouse or partner (compared with the base category living alone; OR 1.35 (95% CI 1.10 to 1.65)), polypharmacy (OR 1.74 (95% CI 1.39 to 2.19)) and frequency of general practitioner visits (compared with the base category 0 visits per year; 1–2 visits OR 2.46 (95% CI 1.80 to 3.35); 3–4 visits OR 3.24 (95% CI 2.34 to 4.47); 5–6 visits OR 2.98 (95% CI 2.08 to 4.26); 7+ visits OR 2.51 (95% CI 1.73 to 3.63)), even after controlling for clinical need. There was no association between using statins and gender, education, income, social class, health insurance status, location or Systematic Coronary Risk Evaluation (SCORE) risk in the multivariable analysis. Conclusion Statin utilisation among those with no history of CVD accounted for almost two-thirds of all statin use, in part reflecting the high proportion of the population with no history of CVD, although utilisation rates were highest among those with a history of CVD.
The psychology of social class: How socioeconomic status impacts thought, feelings, and behaviour

Drawing on recent research on the psychology of social class, I argue that the material conditions in which people grow up and live have a lasting impact on their personal and social identities and that this influences both the way they think and feel about their social environment and key aspects of their social behaviour. Relative to middle‐class counterparts, lower/working‐class individuals are less likely to define themselves in terms of their socioeconomic status and are more likely to have interdependent self‐concepts; they are also more inclined to explain social events in situational terms, as a result of having a lower sense of personal control. Working‐class people score higher on measures of empathy and are more likely to help others in distress. The widely held view that working‐class individuals are more prejudiced towards immigrants and ethnic minorities is shown to be a function of economic threat, in that highly educated people also express prejudice towards these groups when the latter are described as highly educated and therefore pose an economic threat. The fact that middle‐class norms of independence prevail in universities and prestigious workplaces makes working‐class people less likely to apply for positions in such institutions, less likely to be selected and less likely to stay if selected. In other words, social class differences in identity, cognition, feelings, and behaviour make it less likely that working‐class individuals can benefit from educational and occupational opportunities to improve their material circumstances. This means that redistributive policies are needed to break the cycle of deprivation that limits opportunities and threatens social cohesion.
Geodesic Convolutional Shape Optimization

Aerodynamic shape optimization has many industrial applications. Existing methods, however, are so computationally demanding that typical engineering practices are to either simply try a limited number of hand-designed shapes or restrict oneself to shapes that can be parameterized using only few degrees of freedom. In this work, we introduce a new way to optimize complex shapes fast and accurately. To this end, we train Geodesic Convolutional Neural Networks to emulate a fluidynamics simulator. The key to making this approach practical is remeshing the original shape using a polycube map, which makes it possible to perform the computations on GPUs instead of CPUs. The neural net is then used to formulate an objective function that is differentiable with respect to the shape parameters, which can then be optimized using a gradient-based technique. This outperforms state- of-the-art methods by 5 to 20% for standard problems and, even more importantly, our approach applies to cases that previous methods cannot handle.
Temporal Assessment of Molting in Workers of Formosan Subterranean Termites (Isoptera: Rhinotermitidae)

Abstract Molt frequency of workers in laboratory-reared juvenile colonies and foraging population from field colonies of Coptotermes formosanus Shiraki was determined using planar arenas in laboratory. Given that, chitin synthesis inhibitor (CSI)-incorporated baits disrupt the molting process of workers that comprises the major population of a termite colony, temporal assessment of molting frequency in workers can give insights into potential methods of reducing the time to eliminate a CSI-baited colony. In our study the 10-d observation of juvenile colonies of C. formosanus suggested average daily molting incidence of workers in a colony is 1.7 ± 0.3% (mean ± SD). The results from a time lapse study on foraging population of workers showed that on average there is a 44-d intermolt period for second-instar workers molting to third instar and 45 d for third-instar workers molting to fourth instar. At low temperature (21 °C), molting frequency of workers (0.6% per day) was significantly lower than that of workers at 27 °C (2.2% per day). Information from this study suggests that time to molt is an important component of total time for eliminating colonies treated with CSI baits and reduction in time lapse between two consecutive molts may reduce the time required for colony elimination.
Feedback Loops of the Mammalian Circadian Clock Constitute Repressilator

Mammals evolved an endogenous timing system to coordinate their physiology and behaviour to the 24h period of the solar day. While it is well accepted that circadian rhythms are generated by intracellular transcriptional feedback loops, it is still debated which network motifs are necessary and sufficient for generating self-sustained oscillations. Here, we systematically explore a data-based circadian oscillator model with multiple negative and positive feedback loops and identify a series of three subsequent inhibitions known as “repressilator” as a core element of the mammalian circadian oscillator. The central role of the repressilator motif is consistent with time-resolved ChIP-seq experiments of circadian clock transcription factors and loss of rhythmicity in core clock gene knockouts.
Ostomy creation with fewer sutures using tissue adhesives (cyanoacrylates) in inflammatory bowel disease: a pilot study

INTRODUCTION Fistula formation around the ostomy site is a stoma‐related complication often requiring surgical intervention. This complication may be caused by sutures or may develop as a complication of inflammatory bowel disease. Before conducting a clinical trial, we set out to investigate the safety of ostomy creation with fewer sutures using tissue adhesives in this pilot study. METHODS Patients with inflammatory bowel disease who required surgery with ostomy creation at the Hyogo College of Medicine between January 2014 and December 2015 were enrolled. Safety was assessed by evaluating the incidence of stoma‐related complications. Ostomy was restricted to loop ileostomy and was created with two sutures and tissue adhesives. RESULTS A total of 14 patients were enrolled. Mean body mass index was 18.9 ± 2.0 kg/m2. There were no cases of ostomy retraction and no severe adverse events were observed. CONCLUSIONS This pilot study demonstrates that ostomy creation using tissue adhesives is safe. Although retraction and adverse events were not observed, even in patients with inflammatory bowel disease who generally exhibit delayed wound healing, the body mass index was extremely low in this series. This study does not strongly recommend ostomy creation with tissue adhesives; further studies are needed to clarify the efficacy and safety of the procedure.
Pelvic Breadth and Locomotor Kinematics in Human Evolution

A broad pelvis is characteristic of most, if not all, pre‐modern hominins. In at least some early australopithecines, most notably the female Australopithecus afarensis specimen known as “Lucy,” it is very broad and coupled with very short lower limbs. In 1991, Rak suggested that Lucy's pelvic anatomy improved locomotor efficiency by increasing stride length through rotation of the wide pelvis in the axial plane. Compared to lengthening strides by increasing flexion and extension at the hips, this mechanism could avoid potentially costly excessive vertical oscillations of the body's center of mass (COM). Here, we test this hypothesis. We examined 3D kinematics of walking at various speeds in 26 adult subjects to address the following questions: Do individuals with wider pelves take longer strides, and do they use a smaller degree of hip flexion and extension? Is pelvic rotation greater in individuals with shorter legs, and those with narrower pelves? Our results support Rak's hypothesis. Subjects with wider pelves do take longer strides for a given velocity, and for a given stride length they flex and extend their hips less, suggesting a smoother pathway of the COM. Individuals with shorter legs do use more pelvic rotation when walking, but pelvic breadth was not related to pelvic rotation. These results suggest that a broad pelvis could benefit any bipedal hominin, but especially a short‐legged australopithecine such as Lucy, by improving locomotor efficiency, particularly when carrying an infant or traveling in a foraging group with individuals of varying sizes. Anat Rec, 300:739–751, 2017. © 2017 Wiley Periodicals, Inc.
Field Evaluation of Effect of Temperature on Release of Disparlure from a Pheromone-Baited Trapping System used to Monitor Gypsy Moth (Lepidoptera: Lymantriidae)

ABSTRACT Traps baited with disparlure, the synthetic form of the gypsy moth, Lymantria dispar (L.) (Lepidoptera: Lymantriidae), sex pheromone are used to detect newly founded populations and estimate population density across the United States. The lures used in trapping devices are exposed to field conditions with varying climates, which can affect the rate of disparlure release. We evaluated the release rate of disparlure from delta traps baited with disparlure string dispenser from 1 to 3 yr across a broad geographic gradient, from northern Minnesota to southern North Carolina. Traps were deployed over ≈12 wk that coincided with the period of male moth flight and the deployment schedule of traps under gypsy moth management programs. We measured a uniform rate of release across all locations when considered over the accumulation of degree-days; however, due to differences in degree-day accumulation across locations, there were significant differences in release rates over time among locations. The initial lure load seemed to be sufficient regardless of climate, although rapid release of the pheromone in warmer climates could affect trap efficacy in late season. Daily rates of release in colder climates, such as Minnesota and northern Wisconsin, may not be optimal in detection efforts. This work highlights the importance of local temperatures when deploying pheromone-baited traps for monitoring a species across a large and climatically diverse landscape.
Magnificent magpie colours by feathers with layers of hollow melanosomes

ABSTRACT The blue secondary and purple-to-green tail feathers of magpies are structurally coloured owing to stacks of hollow, air-containing melanosomes embedded in the keratin matrix of the barbules. We investigated the spectral and spatial reflection characteristics of the feathers by applying (micro)spectrophotometry and imaging scatterometry. To interpret the spectral data, we performed optical modelling, applying the finite-difference time domain (FDTD) method as well as an effective media approach, treating the melanosome stacks as multi-layers with effective refractive indices dependent on the component media. The differently coloured magpie feathers are realised by adjusting the melanosome size, with the diameter of the melanosomes as well as their hollowness being the most sensitive parameters that influence the appearance of the feathers. Summary: Stacks of rodlet-shaped melanosomes with an air core acting as dielectric multilayers create the striking bright blue or purple-to-green colours of magpie feathers. The spectral properties of the feathers can be quantitatively explained with optical models based on anatomical data.
Opportunities to utilize traditional phenological knowledge to support adaptive management of social-ecological systems vulnerable to changes in climate and fire regimes

The field of adaptive management has been embraced by researchers and managers in the United States as an approach to improve natural resource stewardship in the face of uncertainty and complex environmental problems. Integrating multiple knowledge sources and feedback mechanisms is an important step in this approach. Our objective is to contribute to the limited literature that describes the benefits of better integrating indigenous knowledge (IK) with other sources of knowledge in making adaptive-management decisions. Specifically, we advocate the integration of traditional phenological knowledge (TPK), a subset of IK, and highlight opportunities for this knowledge to support policy and practice of adaptive management with reference to policy and practice of adapting to uncharacteristic fire regimes and climate change in the western United States.
I just scroll through my stuff until I find it or give up: A Contextual Inquiry of PIM on Private Handheld Devices

While ownership and usage of handheld devices such as smartphones and tablets continues to grow at a rapid pace, we do not have complete picture of how people manage personal information on these devices. The few existing studies have typically used interview or survey methods to focus on personal information management (PIM) practices on smartphones. We present the results of an exploratory contextual inquiry study of PIM practices aimed at providing a structured, naturalistic overview of PIM on both smartphones and tablets. We find that people use multiple complementary strategies to acquire different types of information on their devices, and that people rely strongly on automatic chronological ordering instead of organization by subject, although this pays off most for smaller information collections. Deletion of information is strongly influenced by usefulness and personal attachment. Finally, we find that people strongly prefer browsing over search when retrieving information from their devices.
How to make causal inferences using texts

Text as data techniques offer a great promise: the ability to inductively discover measures that are useful for testing social science theories with large collections of text. Nearly all text-based causal inferences depend on a latent representation of the text, but we show that estimating this latent representation from the data creates underacknowledged risks: we may introduce an identification problem or overfit. To address these risks, we introduce a split-sample workflow for making rigorous causal inferences with discovered measures as treatments or outcomes. We then apply it to estimate causal effects from an experiment on immigration attitudes and a study on bureaucratic responsiveness.
The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?

For most of the last century, researchers have searched for a muscle contraction-induced factor that mediates some of the exercise effects in other tissues such as the liver and the adipose tissue. It has been called the ‘work stimulus’, the ‘work factor’ or the ‘exercise factor’. In the search for such a factor, a cytokine, IL-6, was found to be produced by contracting muscles and released into the blood. It has been demonstrated that IL-6 has many biological roles such as: (1) induction of lipolysis; (2) suppression of TNF production; (3) stimulation of cortisol production. The IL-6 gene is rapidly activated during exercise, and the activation of this gene is further enhanced when muscle glycogen content is low. In addition, carbohydrate supplementation during exercise has been shown to inhibit the release of IL-6 from contracting muscle. Thus, it is suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines could be termed ‘myokines’.
Combined assessment of EGFR-related molecules to predict outcome of 1st-line cetuximab-containing chemotherapy for metastatic colorectal cancer

ABSTRACT Several studies have reported that epidermal growth factor receptor (EGFR)-related molecules may serve as predictors of cetuximab treatment for metastatic colorectal cancer (mCRC), such as EGFR gene copy number (GCN), expression of 2 ligands of EGFR, amphiregulin (AREG) and epiregulin (EREG), and EGFR CA simple sequence repeat 1 (CA-SSR1) polymorphism; however, these biomarkers still remain not useful in clinical practice since they have been evaluated using cohorts with patients treated in various settings of chemotherapy. We therefore analyzed associations of mRNA expression of AREG and EREG, EGFR GCN, and CA-SSR1 polymorphism [short (S;≤ 19) / long (L; ≥ 20)] with clinical outcomes in 77 Japanese patients with KRAS exon 2 wild-type mCRC enrolled in phase II trials of FOLFOX (n = 28/57, UMIN000004197) or SOX (n = 49/67, UMIN000007022) plus cetuximab as first-line therapy. High AREG expression correlated with significantly better progression-free survival (median 11.6 vs. 66 months, HR 0.52, P = 0.037); moreover, it remained statistically significant in multivariate analysis (HR: 0.48, P = 0.027). S/S genotype of CA-SSR1 predicted severe skin toxicity (P = 0.040). Patients with both AREG-low and EGFR low-GCN had significantly shorter overall survival than the others (median 22.2 vs. 42.8 months, HR 2.34, P = 0.042). The multivariate analysis showed that molecular status with both AREG-low and EGFR low-GCN was a predictor of worse survival (P = 0.006). In conclusion, AREG mRNA expression and EGFR CA-SSR1 polymorphism predict survival and skin toxicity, respectively, of initial chemotherapy with cetuximab. Our results also suggest potential prognostic value of the combined assessment of AREG and EGFR GCN for first-line cetuximab treatment.