Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia and signs of increased work of breathing are most strongly associated with radiographic pneumonia in children

Commentary on: Shah SN, Bachur RG, Simel DL, et al . Does this child have pneumonia? : the rational clinical examination systematic review. JAMA 2017;318:462–471. Pneumonia remains the predominant cause of childhood mortality beyond the neonatal period.1 Despite the high burden and severity of disease, reliable, feasible reference standards for diagnosis are elusive. Diagnosis in primary care rests on clinical signs, predominantly tachypnoea or lower chest retractions, as contained in WHO guidelines; these signs are sensitive but non-specific.2 This systematic review investigated the accuracy of symptoms and signs to identify children with radiographic pneumonia. This was a systematic review of studies from 1956 to May 2017 of the accuracy of symptoms and clinical signs for diagnosis of paediatric pneumonia as defined by radiographic disease.3 Studies included children <5 years, presentation with suspected pneumonia …
Shivering thermogenesis in the pigeon: the effects of activity, diurnal factors, and feeding state.

Shivering (electromyographic activity of the pectoral muscle), oxygen consumption, and body temperature were measured from undisturbed pigeons for periods of several weeks, and segments from the midparts of each phase of the light-dark cycle were compared at various ambient temperatures and feeding regimes. Behavior was recorded with a video camera. None of the observed types of behavior (e.g., walking, preening, feeding, drinking, pecking, defecation) induced spurious electrical activity in the pectoral muscle. On the other hand, none of these behaviors directly inhibited ongoing shivering. There was no difference in the mean level of shivering between the light (L) and dark (D) phases of the day in any of the conditions, although body temperature was 2°C higher during L. Measurements of integrated electromyogram (EMG) with high temporal resolution (28 samples/s) showed that, at 1°C, shivering in the pectoral muscle was present for more than 98% of the time. Plots of oxygen consumption against root mean square EMG were obtained in each condition by a filtering procedure that excludes data points in which oxygen consumption is affected by motor activity. These plots showed that the increase in heat production induced by a unit increase in pectoral EMG was lower in D than in L and that it was further lowered by fasting. The amplitude spectra of raw EMG signals were similar in all conditions. Spectra of demodulated (rectified, low-pass filtered) EMG showed a distinct rhythmicity around 8 Hz at 21°C that was further enhanced by fasting but absent at 1°C. This suggests that the degree of synchronization and pattern of recruitment of motor units are specific for various temperatures and feeding regimes, and may partly explain the variable relation between heat production and muscle electrical activity. The results emphasize the advantages of long-term measurements for understanding the control of thermogenesis in birds.
So Close and Yet So Irritating: Negative Relations and Implications for Well-being by Age and Closeness.

Objectives Negative social relationships are associated with poor health, chronic illness, and mortality. Yet, we know little about the dynamics of negative aspects of relationships within individual's closest relationships over time, how those experiences vary by age, and the implications of those relationships for well-being. Method A total of 592 participants (ages 25 to 97; M= 57.5; 63.3% women) from the Social Relations Study completed monthly web surveys for up to 12 months. Each month they reported negative relationship quality with their three closest network members and multiple dimensions of well-being (positive affect, negative affect, self-rated health, and sleep quality). Results Multilevel models revealed older individuals reported less negativity in their relationships than younger people, but fewer age differences in the closest tie. Greater negative relationship quality predicted poor well-being (i.e., greater negative affect, sleep problems). Links between negative relations and well-being were less strong among older individuals; especially in the closest ties. Discussion Results were partially consistent with the strength and vulnerability integration (SAVI) model, which proposes fewer age-related improvements in emotion regulation when individuals are unable to avoid tensions. Despite feeling just as negative as younger individuals, older individuals may be more resilient to tensions in their closest relationships.
II. The yin and yang of T cells in intestinal inflammation: pathogenic and protective roles in a mouse colitis model.

Inflammatory bowel disease (IBD) is a multifactorial immune disorder of uncertain etiology. The advent of several mouse models of mucosal inflammation that resemble IBD has provided insight into the mechanisms governing both normal and pathological mucosal immune function. In a widely used adoptive transfer model, the injection into immunodeficient mice of a subset of CD4+ T lymphocytes, the CD4+CD45RBhighcells, leads to inflammation of the intestine. Pathogenesis is due in part to the secretion of proinflammatory cytokines. The induction of colitis can be prevented by cotransfer of another CD4+ subpopulation, the CD4+CD45RBlowT cells. This population behaves analogously to the CD4+CD45RBhighpopulation in terms of the acquisition of activation markers and homing to the host intestine. However, their lymphokine profile when activated is different, and anti-inflammatory cytokines secreted and/or induced by CD4+CD45RBlowT cells prevent colitis. In this themes article, a description of the adoptive transfer model is given, the factors that promote and prevent colitis pathogenesis are discussed, and some controversial aspects of the model are addressed.
Dietary salt increases endothelial nitric oxide synthase and TGF-β1 in rat aortic endothelium.

The amount of NaCl in the diet plays an important role in modulating nitric oxide (NO) synthesis in vivo. In the glomerulus, dietary NaCl also regulates transforming growth factor-β1 (TGF-β1) production. We hypothesized that dietary NaCl intake regulated expression of the endothelial isoform of nitric oxide synthase (NOS3) and TGF-β1 in the aorta. Administration of 8.0% NaCl diet to rats for 7 days did not affect blood pressure but increased steady-state mRNA and protein levels of NOS3 in the arterial wall compared with animals on 0.3% NaCl diet. Northern analysis demonstrated increased steady-state amounts of mRNA of TGF-β1 in aortas of rats on 8.0% NaCl diet. By ELISA, both total and active TGF-β1 were increased in these vessel segments. Endothelial denudation of aortic rings reduced active TGF-β1 secretion to undetectable levels. Addition of a neutralizing antibody to TGF-β to aortic ring segments attenuated NO production but not to that observed in animals on the 0.3% NaCl diet. The data showed that dietary NaCl intake modulated NOS3 and TGF-β1 expression in the arterial wall; NOS3 expression was at least partially regulated by endothelial cell production of TGF-β1.
Sieve: actionable insights from monitored metrics in distributed systems

Major cloud computing operators provide powerful monitoring tools to understand the current (and prior) state of the distributed systems deployed in their infrastructure. While such tools provide a detailed monitoring mechanism at scale, they also pose a significant challenge for the application developers/operators to transform the huge space of monitored metrics into useful insights. These insights are essential to build effective management tools for improving the efficiency, resiliency, and dependability of distributed systems. This paper reports on our experience with building and deploying Sieve---a platform to derive actionable insights from monitored metrics in distributed systems. Sieve builds on two core components: a metrics reduction framework, and a metrics dependency extractor. More specifically, Sieve first reduces the dimensionality of metrics by automatically filtering out unimportant metrics by observing their signal over time. Afterwards, Sieve infers metrics dependencies between distributed components of the system using a predictive-causality model by testing for Granger Causality. We implemented Sieve as a generic platform and deployed it for two microservices-based distributed systems: OpenStack and Share-Latex. Our experience shows that (1) Sieve can reduce the number of metrics by at least an order of magnitude (10 -- 100×), while preserving the statistical equivalence to the total number of monitored metrics; (2) Sieve can dramatically improve existing monitoring infrastructures by reducing the associated overheads over the entire system stack (CPU---80%, storage---90%, and network---50%); (3) Lastly, Sieve can be effective to support a wide-range of workflows in distributed systems---we showcase two such workflows: Orchestration of autoscaling, and Root Cause Analysis (RCA).
Pyruvate augments calcium transients and cell shortening in rat ventricular myocytes.

Pyruvate has been shown to be a metabolic inotrope in the myocardium. In millimolar concentrations, it has been shown to increase both myocardial phosphorylation potential and the cytosolic [NAD+]-to-[NADH] ratio. To determine if changes in these parameters can alter intracellular Ca2+ concentration ([Ca2+]i) and hence contractile function, Ca2+ transients and cell shortening (CS) were measured in isolated rat ventricular myocytes superfused with a physiological N-2-hydroxyethylpiperazine- N'-2-ethanesulfonic acid buffer (11 mmol/l glucose) with and without additional pyruvate,l-lactate, acetate, or isoproterenol. The addition of 5 mmol/l pyruvate resulted in a 33% increase in CS and a 39% increase in systolic [Ca2+]i. These pyruvate effects were 70% of those observed with 100 nmol/l isoproterenol. The mitochondrial monocarboxylate transport inhibitor α-cyano-4-hydroxycinnamate (250 μmol/l) strongly inhibited pyruvate inotropy, suggesting a substantial obligatory coupling between pyruvate inotropism and its oxidation by the mitochondria. A possible role of the cytosolic [NAD+]-to-[NADH] ratio was assessed by comparing the effects of 20 mmol/ll-lactate to those of equimolar pyruvate. In contrast to 20 mmol/l pyruvate, excess l-lactate failed to appreciably increase CS or systolic [Ca2+]i. The findings imply that, at levels substantially above 5 mmol/l, a portion of pyruvate inotropism might be due to extreme cytosolic [NAD+]-to-[NADH] ratios. This study is the first evidence that augmented [Ca2+]itransients are most likely the mechanism of cardiac pyruvate inotropism.
Nectary tracks as pollinator manipulators: The pollination ecology of Swertia bimaculata (Gentianaceae)

Abstract Floral nectaries are closely associated with biotic pollination, and the nectar produced by corolla nectaries is generally enclosed in floral structures. Although some Swertia spp. (Gentianaceae), including S. bimaculata, evolved a peculiar form of corolla nectaries (known as “gland patches”) arranged in a conspicuous ring on the rotate corolla and that completely expose their nectar, little is known about the pollination of these plants. Two hypotheses were made concerning the possible effects of gland patches: visual attraction and visitor manipulation. The floral traits, mating system, and insect pollination of S. bimaculata were examined, and the pollination effects of gland patches were evaluated. A comparative study was made using Swertia kouitchensis, a species with fimbriate nectaries. Swertia bimaculata flowers were protandrous, with obvious stamen movement leading to herkogamy in the female phase and to a significant reduction in nectary–anther distance. The species is strongly entomophilous and facultatively xenogamous. The daily reward provided per flower decreased significantly after the male phase. The most effective pollinators were large dipterans, and the visiting proportion of Diptera was significantly higher in S. bimaculata than in S. kouitchensis. Most visitors performed “circling behavior” in S. bimaculata flowers. Removing or blocking the nectaries caused no reduction in visiting frequency but a significant reduction in visit duration, interrupting the circling behavior. The circling behavior was encouraged by nectar abundance and promoted pollen dispersal. Visitor species with small body size had little chance to contact the anthers or stigma, revealing a filtration effect exerted by the floral design. These results rejected the “visual attraction” hypothesis and supported the “visitor manipulation” hypothesis. The nectary whorl within a flower acted like a ring‐shaped track that urged nectar foragers to circle on the corolla, making pollination in S. bimaculata flowers more orderly and selective than that in classically generalist flowers.
Modeling the dynamics of oligodendrocyte precursor cells and the genesis of gliomas

Oligodendrocyte precursor cells (OPCs) have remarkable properties: they represent the most abundant cycling cell population in the adult normal brain and they manage to achieve a uniform and constant density throughout the adult brain. This equilibrium is obtained by the interplay of four processes: division, differentiation or death, migration and active self-repulsion. They are also strongly suspected to be at the origin of gliomas, when their equilibrium is disrupted. In this article, we present a model of the dynamics of OPCs, first in a normal tissue. This model is based on a cellular automaton and its rules are mimicking the ones that regulate the dynamics of real OPCs. The model is able to reproduce the homeostasis of the cell population, with the maintenance of a constant and uniform cell density and the healing of a lesion. We show that there exists a fair quantitative agreement between the simulated and experimental parameters, such as the cell velocity, the time taken to close a lesion, and the duration of the cell cycle. We present three possible scenarios of disruption of the equilibrium: the appearance of an over-proliferating cell, of a deadless/non-differentiating cell, or of a cell that lost any contact-inhibition. We show that the appearance of an over-proliferating cell is sufficient to trigger the growth of a tumor that has low-grade glioma features: an invasive behaviour, a linear radial growth of the tumor with a corresponding growth velocity of less than 2 mm per year, as well a cell density at the center which exceeds the one in normal tissue by a factor of less than two. The loss of contact inhibition leads to a more high-grade-like glioma. The results of our model contribute to the body of evidence that identify OPCs as possible cells of origin of gliomas.
Investigation of the genotoxic and cytotoxic effects of widely used neonicotinoid insecticides in HepG2 and SH-SY5Y cells

Neonicotinoids are a relatively new type of insecticide to control a variety of pests. Although they are generally considered to be safe, they can lead to harmful effects on human and environmental health. We aimed to investigate possible effects of common neonicotinoid insecticides (acetamiprid, clothianidin, imidacloprid, thiacloprid, and thiamethoxam) on cytotoxicity and DNA damage in human neuroblastoma (SH-SY5Y) and human hepatocellular carcinoma (HepG2) cells. Our results indicated that 50% of inhibitory concentration values of neonicotinoids are in the range of 0.96 to >4 mM in SH-SY5Y cells and 0.53 to >4 mM in HepG2 cells by the methyl tetrazolium and neutral red uptake tests after 24 and 48 h exposure. We observed significant DNA damage at 500 µM of five neonicotinoids in SHSY-5Y cells, while only imidacloprid, thiametoxam, and thiacloprid showed some alterations in HepG2 cells after 24 h exposure using the alkaline comet assay. In conclusion, neonicotinoid insecticides may induce cytotoxicity and DNA damage in cell cultures; therefore, further studies are needed to better understand the toxicity of neonicotinoids.
P450 Pharmacogenetics in Indigenous North American Populations

Indigenous North American populations, including American Indian and Alaska Native peoples in the United States, the First Nations, Métis and Inuit peoples in Canada and Amerindians in Mexico, are historically under-represented in biomedical research, including genomic research on drug disposition and response. Without adequate representation in pharmacogenetic studies establishing genotype-phenotype relationships, Indigenous populations may not benefit fully from new innovations in precision medicine testing to tailor and improve the safety and efficacy of drug treatment, resulting in health care disparities. The purpose of this review is to summarize and evaluate what is currently known about cytochrome P450 genetic variation in Indigenous populations in North America and to highlight the importance of including these groups in future pharmacogenetic studies for implementation of personalized drug therapy.
Sensitivity Enhancement of Surface Plasmon Resonance Imaging Using Periodic Metallic Nanowires

A nanowire-mediated surface plasmon resonance (SPR) imaging is numerically investigated for enhanced sensitivity. The results calculated by rigorous coupled-wave analysis present that interplays between localized surface plasmons and surface plasmon polaritons contribute to sensitivity enhancement. Compared to conventional thin film-based SPR imaging measurement, an optimal nanowire structure can provide sensitivity enhancement by 3.44 times as well as highly linear detection property for quantification of surface reactions of interests. This paper demonstrates the potential and limitation for a highly sensitive, label-free, and real-time SPR imaging sensor based on periodic metallic nanowires.
Cell Therapy for Stroke: Review of Previous Clinical Trials and Introduction of Our New Trials

Stroke is still a leading cause of death and disability, and despite intensive research, few treatment options exist. A recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Although some pioneer studies on the use of cell therapy for the treatment of stroke have been reported, certain problems still remain unsolved. We investigated the use of autologous bone marrow stromal cell (BMSC) transplantation for the treatment of stroke, to develop it as the next-generation cell therapy. In this study, we introduce the preparation of a new clinical trial, the Research on Advanced Intervention using Novel Bone marrow stem cell (RAINBOW) study. The trial will start in 2016, and we hope that it will not only be helpful for treating patients but also for clarifying the therapeutic mechanisms. Moreover, we review stem cell therapeutics as an emerging paradigm in stroke (STEPS) and the guidelines for the development of cell therapy for stroke in the United States as well as introduce the development of new guidelines in Japan. These guidelines are expected to encourage the development of cell therapy for stroke management.
Reconstructing Interlaced High-Dynamic-Range Video Using Joint Learning

For extending the dynamic range of video, it is a common practice to capture multiple frames sequentially with different exposures and combine them to extend the dynamic range of each video frame. However, this approach results in typical ghosting artifacts due to fast and complex motion in nature. As an alternative, video imaging with interlaced exposures has been introduced to extend the dynamic range. However, the interlaced approach has been hindered by jaggy artifacts and sensor noise, leading to concerns over image quality. In this paper, we propose a data-driven approach for jointly solving two specific problems of deinterlacing and denoising that arise in interlaced video imaging with different exposures. First, we solve the deinterlacing problem using joint dictionary learning via sparse coding. Since partial information of detail in differently exposed rows is often available via interlacing, we make use of the information to reconstruct details of the extended dynamic range from the interlaced video input. Second, we jointly solve the denoising problem by tailoring sparse coding to better handle additive noise in low-/high-exposure rows, and also adopt multiscale homography flow to temporal sequences for denoising. We anticipate that the proposed method will allow for concurrent capture of higher dynamic range video frames without suffering from ghosting artifacts. We demonstrate the advantages of our interlaced video imaging compared with the state-of-the-art high-dynamic-range video methods.
Homologous recombination and the repair of DNA double-strand breaks

Homologous recombination enables the cell to access and copy intact DNA sequence information in trans, particularly to repair DNA damage affecting both strands of the double helix. Here, we discuss the DNA transactions and enzymatic activities required for this elegantly orchestrated process in the context of the repair of DNA double-strand breaks in somatic cells. This includes homology search, DNA strand invasion, repair DNA synthesis, and restoration of intact chromosomes. Aspects of DNA topology affecting individual steps are highlighted. Overall, recombination is a dynamic pathway with multiple metastable and reversible intermediates designed to achieve DNA repair with high fidelity.
Subjective Social Status Predicts Late-Life Memory Trajectories through Both Mental and Physical Health Pathways

Background: Subjective social status (SSS) is associated with mental and physical health, independent of objective socioeconomic status (SES), but its association with late-life cognitive decline is unknown. Objective: This study characterizes the association between SSS and late-life memory trajectories in a large, nationally representative sample of older adults in the United States. Methods: Using data from 8,530 participants aged 65 years and older in the Health and Retirement Study, structural equation models tested associations between SSS, objective SES (i.e., educational attainment, occupation, income, and wealth), physical and mental health, and 6-year memory trajectories, controlling for sociodemographic characteristics. Results: Independent of objective SES, lower SSS was associated with worse initial memory but not subsequent memory decline. The association between SSS and initial memory was separately mediated by chronic diseases, stroke, and depressive symptoms. Conclusion: Results provide preliminary behavioral evidence for the deleterious effects of social stress on cognitive aging. These results may help inform the development of policies and interventions to reduce cognitive morbidity among older adults who perceive a low position on the social hierarchy.
Centrally mediated effect of 17β-estradiol on parasympathetic tone in male rats.

The following experiments were conducted to determine if peripherally administered estrogen has an effect on central autonomic tone and whether this change in tone results in an alteration in cardiovascular reflex control. Male Sprague-Dawley rats were anesthetized with thiobutabarbitol sodium (50 mg/kg) and instrumented to record blood pressure, heart rate, and vagal parasympathetic or renal sympathetic efferent nerve activity. Additional rats were instrumented to test the sensitivity of the cardiac baroreflex using intravenous injections of phenylephrine hydrochloride (0.025, 0.05, 0.1 mg/kg) or sodium nitroprusside (0.0025, 0.005, 0.01 mg/kg) and plotting the cardiovascular responses. Intravenous injection of estrogen (10-4, 10-2, and 10-1 mg/kg) produced a significant increase in vagal efferent activity and in baroreflex sensitivity. The bilateral microinjection of an estrogen receptor antagonist, ICI-182,780 (1 pM, 50 nl/side) into the nucleus ambiguus blocked both the estrogen-induced increase in vagal efferent activity and baroreflex sensitivity. These results demonstrate that in male rats estrogen acts centrally to enhance baroreflex sensitivity by increasing parasympathetic efferent tone.