Miracle-dz/UniFAR-FTUs huggingface dataset:
Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment

Erythropoiesis stimulating agents are widely used for the treatment of anemia. Recently, we reported erythroid expansion with impaired B lymphopoiesis and loss of trabecular bone in C57BL/6 mice following ten days of treatment with low-dose short acting recombinant human erythropoietin. We have assessed erythropoietin against longer-acting darbepoietin-alfa at a comparable erythroid stimulatory dosage regime. Darbepoietin-alfa and erythropoietin induced similar in vivo erythropoietic expansion. Both agents induced an expansion of the colony-forming unit-erythroid populations. However, unlike erythropoietin, darbepoietin-alfa did not impair bone marrow B lymphopoiesis. Strikingly the bone loss observed with erythropoietin was not apparent following darbepoietin-alfa treatment. This analysis demonstrates that whilst darbepoietin-alfa has similar in vivo erythropoietic potency to erythropoietin, it preserves the bone marrow microenvironment. Thus erythropoietin and darbepoietin-alfa manifest different action showing that erythropoiesis stimulating agents have differential non-erythroid effects dependent on their duration of action.
Computer Vision-Based Carbohydrate Estimation for Type 1 Patients With Diabetes Using Smartphones

Background: Individuals with type 1 diabetes (T1D) have to count the carbohydrates (CHOs) of their meal to estimate the prandial insulin dose needed to compensate for the meal’s effect on blood glucose levels. CHO counting is very challenging but also crucial, since an error of 20 grams can substantially impair postprandial control. Method: The GoCARB system is a smartphone application designed to support T1D patients with CHO counting of nonpacked foods. In a typical scenario, the user places a reference card next to the dish and acquires 2 images with his/her smartphone. From these images, the plate is detected and the different food items on the plate are automatically segmented and recognized, while their 3D shape is reconstructed. Finally, the food volumes are calculated and the CHO content is estimated by combining the previous results and using the USDA nutritional database. Results: To evaluate the proposed system, a set of 24 multi-food dishes was used. For each dish, 3 pairs of images were taken and for each pair, the system was applied 4 times. The mean absolute percentage error in CHO estimation was 10 ± 12%, which led to a mean absolute error of 6 ± 8 CHO grams for normal-sized dishes. Conclusion: The laboratory experiments demonstrated the feasibility of the GoCARB prototype system since the error was below the initial goal of 20 grams. However, further improvements and evaluation are needed prior launching a system able to meet the inter- and intracultural eating habits.
Commodity Packet Capture Engines: Tutorial, Cookbook and Applicability

Users' demands have dramatically increased due to widespread availability of broadband access and new Internet avenues for accessing, sharing and working with information. In response, operators have upgraded their infrastructures to survive in a market as mature as the current Internet. This has meant that most network processing tasks (e.g., routing, anomaly detection, monitoring) must deal with challenging rates, challenges traditionally accomplished by specialized hardware-e.g., FPGA. However, such approaches lack either flexibility or extensibility-or both. As an alternative, the research community has proposed the utilization of commodity hardware providing flexible and extensible cost-aware solutions, thus entailing lower operational and capital expenditure investments. In this scenario, we explain how the arrival of commodity packet engines has revolutionized the development of traffic processing tasks. Thanks to the optimization of both NIC drivers and standard network stacks and by exploiting concepts such as parallelism and memory affinity, impressive packet capture rates can be achieved in hardware valued at a few thousand dollars. This tutorial explains the foundation of this new paradigm, i.e., the knowledge required to capture packets at multi-Gb/s rates on commodity hardware. Furthermore, we thoroughly explain and empirically compare current proposals, and importantly explain how apply such proposals with a number of code examples. Finally, we review successful use cases of applications developed over these novel engines.
Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25–70 years from ten European countries in 1992–2000. Information on coffee and tea drinking was collected at baseline using validated country‐specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow‐up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non‐consumers 0.31, 95% CI 0.14–0.69) but not among women (HR 0.96, 95% CI 0.62–1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.
Secretory phospholipase A2 in the pathogenesis of acute dengue infection

Platelet activating factor (PAF) is an important mediator of vascular leak in acute dengue. Phospholipase A2s (PLA2) are inflammatory lipid enzymes that generate and regulate PAF and other mediators associated with mast cells. We sought to investigate if mast cell activation and increases in secretory sPLA2s are associated with an increase in PAF and occurrence of dengue haemorrhagic fever (DHF).
Childhood intelligence in relation to major causes of death in 68 year follow-up: prospective population study

Objectives To examine the association between intelligence measured in childhood and leading causes of death in men and women over the life course. Design Prospective cohort study based on a whole population of participants born in Scotland in 1936 and linked to mortality data across 68 years of follow-up. Setting Scotland. Participants 33 536 men and 32 229 women who were participants in the Scottish Mental Survey of 1947 (SMS1947) and who could be linked to cause of death data up to December 2015. Main outcome measures Cause specific mortality, including from coronary heart disease, stroke, specific cancer types, respiratory disease, digestive disease, external causes, and dementia. Results Childhood intelligence was inversely associated with all major causes of death. The age and sex adjusted hazard ratios (and 95% confidence intervals) per 1 SD (about 15 points) advantage in intelligence test score were strongest for respiratory disease (0.72, 0.70 to 0.74), coronary heart disease (0.75, 0.73 to 0.77), and stroke (0.76, 0.73 to 0.79). Other notable associations (all P<0.001) were observed for deaths from injury (0.81, 0.75 to 0.86), smoking related cancers (0.82, 0.80 to 0.84), digestive disease (0.82, 0.79 to 0.86), and dementia (0.84, 0.78 to 0.90). Weak associations were apparent for suicide (0.87, 0.74 to 1.02) and deaths from cancer not related to smoking (0.96, 0.93 to 1.00), and their confidence intervals included unity. There was a suggestion that childhood intelligence was somewhat more strongly related to coronary heart disease, smoking related cancers, respiratory disease, and dementia in women than men (P value for interactions <0.001, 0.02, <0.001, and 0.02, respectively). Childhood intelligence was related to selected cancer presentations, including lung (0.75, 0.72 to 0.77), stomach (0.77, 0.69 to 0.85), bladder (0.81, 0.71 to 0.91), oesophageal (0.85, 0.78 to 0.94), liver (0.85, 0.74 to 0.97), colorectal (0.89, 0.83 to 0.95), and haematopoietic (0.91, 0.83 to 0.98). Sensitivity analyses on a representative subsample of the cohort observed only small attenuation of the estimated effect of intelligence (by 10-26%) after adjustment for potential confounders, including three indicators of childhood socioeconomic status. In a replication sample from Scotland, in a similar birth year cohort and follow-up period, smoking and adult socioeconomic status partially attenuated (by 16-58%) the association of intelligence with outcome rates. Conclusions In a whole national population year of birth cohort followed over the life course from age 11 to age 79, higher scores on a well validated childhood intelligence test were associated with lower risk of mortality ascribed to coronary heart disease and stroke, cancers related to smoking (particularly lung and stomach), respiratory diseases, digestive diseases, injury, and dementia.
The Botrytis cinerea elicitor protein BcIEB1 interacts with the tobacco PR5-family protein osmotin and protects the fungus against its antifungal activity.

The broad-range phytopathogenic fungus Botrytis cinerea secretes hundreds of proteins during infection of its plant hosts. One of these proteins, BcIEB1, is abundantly secreted and is able to elicit plant defenses, probably as a pathogen-associated molecular pattern, although its native function in B. cinerea biology remains unknown. Pull-down experiments designed to isolate the molecular target of BcIEB1 in tobacco resulted in the identification of osmotin, a pathogenesis-related protein of family 5 that shows antifungal activity. The expression of osmotin in Escherichia coli allowed the verification of the BcIEB1-osmotin interaction with pure proteins by pull-down and far Western blot experiments, as well as the confirmation of the activity of osmotin against B. cinerea. Interestingly, B. cinerea Δbcieb1 mutants are more susceptible than the wild-type to osmotin, and the external addition of pure BcIEB1 protects the Δbcieb1 mutants, as well as Saccharomyces cerevisiae, from the antifungal action of osmotin, thus pointing at PR5 inhibition as the primary native function of BcIEB1. The question of whether osmotin is also involved in the activation of plant defenses by BcIEB1 is also addressed, and the data suggest that osmotin does not participate in the elicitation process.
Behavioral contagion during learning about another agent’s risk-preferences acts on the neural representation of decision-risk

Significance Why do we on some occasions engage in risky behavior but not on other occasions? Here, we explore the neural mechanisms of one possible account: a contagion effect. Using neuroimaging combined with computational modeling, we show that if we observe others behaving in a risk-seeking/risk-averse fashion, we become in turn more/less prone to risky behavior, and the behavioral shift is specifically implemented via neural processing of risk in a brain region, caudate nucleus. We further show that functional connectivity between the caudate and the dorsolateral prefrontal cortex, a region implicated in learning about others’ risk-attitude, is associated with susceptibility to the contagion effect, providing an account for how our own behavior can be influenced through observing other agents. Our attitude toward risk plays a crucial role in influencing our everyday decision-making. Despite its importance, little is known about how human risk-preference can be modulated by observing risky behavior in other agents at either the behavioral or the neural level. Using fMRI combined with computational modeling of behavioral data, we show that human risk-preference can be systematically altered by the act of observing and learning from others’ risk-related decisions. The contagion is driven specifically by brain regions involved in the assessment of risk: the behavioral shift is implemented via a neural representation of risk in the caudate nucleus, whereas the representations of other decision-related variables such as expected value are not affected. Furthermore, we uncover neural computations underlying learning about others’ risk-preferences and describe how these signals interact with the neural representation of risk in the caudate. Updating of the belief about others’ preferences is associated with neural activity in the dorsolateral prefrontal cortex (dlPFC). Functional coupling between the dlPFC and the caudate correlates with the degree of susceptibility to the contagion effect, suggesting that a frontal–subcortical loop, the so-called dorsolateral prefrontal–striatal circuit, underlies the modulation of risk-preference. Taken together, these findings provide a mechanistic account for how observation of others’ risky behavior can modulate an individual’s own risk-preference.
Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD

Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over‐responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity during exposure to aversive sensory inputs in individuals with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in atypical sensory processing given its role in selective attention, regulation, and sensory integration. This study aimed to examine the role of pulvinar connectivity in ASD during mildly aversive sensory input. Functional magnetic resonance imaging was used to examine connectivity with the pulvinar during exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9–17; 19 ASD, 19 IQ‐matched typically developing (TD)). Parents rated children's SOR severity on two standard scales. Compared to TD, ASD participants displayed aberrant modulation of connectivity between pulvinar and cortex (including sensory‐motor and prefrontal regions) during sensory stimulation. In ASD participants, pulvinar‐amygdala connectivity was correlated with severity of SOR symptoms. Deficits in modulation of thalamocortical connectivity in youth with ASD may reflect reduced thalamo‐cortical inhibition in response to sensory stimulation, which could lead to difficulty filtering out and/or integrating sensory information. An increase in amygdala connectivity with the pulvinar might be partially responsible for deficits in selective attention as the amygdala signals the brain to attend to distracting sensory stimuli. Autism Res 2017, 10: 801–809. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Against the Political Exclusion of the Incapable

Political exclusion on grounds of incapacity is the primary remaining source of exclusion from the franchise. It is appealed to by states and theorists alike to justify excluding young people (under 18) and many people with cognitive disability from the franchise. Defenders of this exclusion claim that no wrong is done by this exclusion and that states gain some significant benefits from this restricting of the franchise. I have argued elsewhere that political exclusion as currently practiced in modern liberal democratic states in fact causes significant harms, as it excludes some people who have the relevant capacity for political participation. Here, I argue that the exclusion of incapable actors prevents no significant harms to democratic outcomes, and that it confers no significant democratic benefits on the states practising this exclusion. As such, I argue that we ought to heavily modify and perhaps even abandon the capacity standard for political inclusion.
Low-dose methotrexate in myeloproliferative neoplasm models

In recent years gain-of-function driver mutations in JAK2, MPL and CALR have been identified that constitutively activate janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway signaling. Collectively, these mutations lead to the development of the vast majority of myeloproliferative neoplasms (MPNs), a group of related diseases including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). Patients with MPNs have higher mortality rates, primarily due to cardiovascular complications, infections and transformation to other hematological malignancies such as leukemias. They also suffer significant constitutional symptoms including pruritus, headaches, weight loss, loss of appetite, fatigue and night sweats. Current MPN therapeutics include venesection to control blood counts in PV, aspirin to reduce the risk of thrombosis in both PV and ET, and cytoreductive agents such as hydroxycarbamide to
Clinical predictors of the estimated glomerular filtration rate 1 year after radical nephrectomy in Japanese patients

Purpose To evaluate renal function 1 year after radical nephrectomy (RN) for renal cell carcinoma, the preoperative predictors of postnephrectomy renal function were investigated by sex, and equations to predict the estimated glomerular filtration rate (eGFR) 1 year after RN were developed. Materials and Methods A total of 525 patients who underwent RN between May 2007 and August 2011 at Tohoku University Hospital and its affiliated hospitals were prospectively evaluated. Overall, 422 patients were analyzed in this study. Results Independent preoperative factors associated with postnephrectomy renal function were different in males and females. Preoperative eGFR, age, tumor size, and body mass index (BMI) were independent factors in males, while tumor size and BMI were not independent factors in females. The equations developed to predict eGFR 1 year after RN were: Predicted eGFR in males (mL/min/1.73 m2)=27.99−(0.196×age)+(0.497×eGFR)+(0.744×tumor size)−(0.339×BMI); and predicted eGFR in females=44.57−(0.275×age)+(0.298×eGFR). The equations were validated in the validation dataset (R2=0.63, p<0.0001 and R2=0.31, p<0.0001, respectively). Conclusions The developed equations by sex enable better prediction of eGFR 1 year after RN. The equations will be useful for preoperative patient counseling and selection of the type of surgical procedure in elective partial or RN cases.
Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru.

Painschab, Matthew S. , Gary E. Malpartida, Victor G. Davila-Roman, Robert H. Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William Checkley. Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt Med Biol 16:26-33, 2015. -Long-term residence at high altitude is associated with the development of chronic mountain sickness (CMS), which is characterized by excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly selected mutation in hypoxia-inducible factor 2α (HIF2A) has been found in native Tibetans that correlates with having a normal hemoglobin at high altitude. We sought to evaluate differences in plasma levels of four HIF-responsive proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women) and in 20 healthy, age- and sex-matched participants without EE living at high altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we evaluated the association between HIF-responsive proteins and echocardiography-estimated pulmonary artery systolic pressure (PASP) in a subset of 26 participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107 pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1, VEGF, and erythropoietin were higher in participants with vs. without EE, they did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and erythropoietin (p=0.04) were positively associated with PASP after adjustment for age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in altitude-related, chronic diseases but our results did not show consistent changes in all measured HIF-responsive proteins. Larger studies are needed to evaluate for additional genetic and environmental risk factors.
Altered eye‐to‐foot coordination in standing parkinsonian patients during large gaze and whole‐body reorientations

We investigated whether turning problems in Parkinson's disease may be the result of abnormal horizontal multisegmental angular coordination. Ten mildly affected patients and controls stood upright and voluntarily reoriented eyes and body to illuminated targets of eccentricities up to ±180 degrees. The effects of target location, visibility, and predictability on movement parameters were evaluated. Patients' latencies were normal. Control subjects foveated large eccentricity targets with a single gaze shift in approximately 30% of predictable trials. Patients rarely did so (10% of predictable trials) because of reduced head‐in‐space and trunk velocity. This resulted in massive foveation delays in patients—an average of half a second for displacements of 180 degrees. The covariation of eye, head, and trunk rotations was quantified statistically by means of principal components analysis. In both groups, the combined movement was initially stereotyped and two principal components accounted for nearly all data variance—the original three mechanical degrees of freedom (i.e., eye‐head‐trunk) are reduced to two kinematic degrees of freedom. However, in patients, the eye contributed more, and the head and trunk less, to the gaze shift than in control subjects. Although the eye‐to‐foot turning synergy is preserved in early‐stage parkinsonism, quantitative differences are prominent, particularly a larger ocular (and smaller head‐trunk) contribution in patients. Turning problems in Parkinson's disease do not result from inability to assemble multisegmental movements, as patients' ability to control numerous degrees of freedom is preserved. However, trunk bradykinesia reduces the frequency of single‐step gaze shifts, thus prolonging target acquisition time. Preserved eye motion compensates for trunk slowness. © 2011 Movement Disorder Society