julilili42/papers huggingface dataset:
Transcription and Translation Inhibitors in Cancer Treatment
2020-04-21

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.
The Low/High Index of Pupillary Activity
2020-04-21

A novel eye-tracked measure of pupil diameter oscillation is derived as an indicator of cognitive load. The new metric, termed the Low/High Index of Pupillary Activity (LHIPA), is able to discriminate cognitive load (vis-a-vis task difficulty) in several experiments where the Index of Pupillary Activity fails to do so. Rationale for the LHIPA is tied to the functioning of the human autonomic nervous system yielding a hybrid measure based on the ratio of Low/High frequencies of pupil oscillation. The paper's contribution is twofold. First, full documentation is provided for the calculation of the LHIPA. As with the IPA, it is possible for researchers to apply this metric to their own experiments where a measure of cognitive load is of interest. Second, robustness of the LHIPA is shown in analysis of three experiments, a restrictive fixed-gaze number counting task, a less restrictive fixed-gaze n-back task, and an applied eye-typing task.
Gibbs and Boltzmann Entropy in Classical and Quantum Mechanics
2020-04-21

The Gibbs entropy of a macroscopic classical system is a function of a probability distribution over phase space, i.e., of an ensemble. In contrast, the Boltzmann entropy is a function on phase space, and is thus defined for an individual system. Our aim is to discuss and compare these two notions of entropy, along with the associated ensemblist and individualist views of thermal equilibrium. Using the Gibbsian ensembles for the computation of the Gibbs entropy, the two notions yield the same (leading order) values for the entropy of a macroscopic system in thermal equilibrium. The two approaches do not, however, necessarily agree for non-equilibrium systems. For those, we argue that the Boltzmann entropy is the one that corresponds to thermodynamic entropy, in particular, in connection with the second law of thermodynamics. Moreover, we describe the quantum analog of the Boltzmann entropy, and we argue that the individualist (Boltzmannian) concept of equilibrium is supported by the recent works on thermalization of closed quantum systems.
Neuroimaging of hypothalamic mechanisms related to glucose metabolism in anorexia nervosa and obesity
2020-04-21

BACKGROUNDGiven the heightened tolerance to self-starvation in anorexia nervosa (AN), a hypothalamic dysregulation of energy and glucose homeostasis has been hypothesized. Therefore, we investigated whether hypothalamic reactivity to glucose metabolism is impaired in AN.METHODSTwenty-four participants with AN, 28 normal-weight participants, and 24 healthy participants with obesity underwent 2 MRI sessions in a single-blind, randomized, case-controlled crossover study. We used an intragastric infusion of glucose and water to bypass the cephalic phase of food intake. The responsivity of the hypothalamus and the crosstalk of the hypothalamus with reward-related brain regions were investigated using high-resolution MRI.RESULTSNormal-weight control participants displayed the expected glucose-induced deactivation of hypothalamic activation, whereas patients with AN and participants with obesity showed blunted hypothalamic reactivity. Furthermore, patients with AN displayed blunted reactivity in the nucleus accumbens and amygdala. Compared with the normal-weight participants and control participants with obesity, the patients with AN failed to show functional connectivity between the hypothalamus and the reward-related brain regions during water infusion relative to glucose infusion. Finally, the patients with AN displayed typical baseline levels of peripheral appetite hormones during a negative energy balance.CONCLUSIONThese results indicate that blunted hypothalamic glucose reactivity might be related to the pathophysiology of AN. This study provides insights for future research, as it is an extended perspective of the traditional primary nonhomeostatic understanding of the disease.FUNDINGThis study was supported by a grant from the DFG (SI 2087/2-1).
Predicting Perturbed Human Arm Movements in a Neuro-Musculoskeletal Model to Investigate the Muscular Force Response
2020-04-21

Human movement is generated by a dynamic interplay between the nervous system, the biomechanical structures, and the environment. To investigate this interaction, we propose a neuro-musculoskeletal model of human goal-directed arm movements. Using this model, we simulated static perturbations of the inertia and damping properties of the arm, as well as dynamic torque perturbations for one-degree-of freedom movements around the elbow joint. The controller consists of a feed-forward motor command and feedback based on muscle fiber length and contraction velocity representing short-latency (25 ms) or long-latency (50 ms) stretch reflexes as the first neuronal responses elicited by an external perturbation. To determine the open-loop control signal, we parameterized the control signal resulting in a piecewise constant stimulation over time for each muscle. Interestingly, such an intermittent open-loop signal results in a smooth movement that is close to experimental observations. So, our model can generate the unperturbed point-to-point movement solely by the feed-forward command. The feedback only contributed to the stimulation in perturbed movements. We found that the relative contribution of this feedback is small compared to the feed-forward control and that the characteristics of the musculoskeletal system create an immediate and beneficial reaction to the investigated perturbations. The novelty of these findings is (1) the reproduction of static as well as dynamic perturbation experiments in one neuro-musculoskeletal model with only one set of basic parameters. This allows to investigate the model's neuro-muscular response to the perturbations that-at least to some degree-represent stereotypical interactions with the environment; (2) the demonstration that in feed-forward driven movements the muscle characteristics generate a mechanical response with zero-time delay which helps to compensate for the perturbations; (3) that this model provides enough biomechanical detail to allow for the prediction of internal forces, including joint loads and muscle-bone contact forces which are relevant in ergonomics and for the development of assistive devices but cannot be observed in experiments.
Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices
2020-04-21

Human cerebrospinal fluid (hCSF) has proven advantageous over conventional medium for culturing both rodent and human brain tissue. In addition, increased activity and synchrony, closer to the dynamic states exclusively recorded <i>in vivo</i>, were reported in rodent slices and cell cultures switching from artificial cerebrospinal fluid (aCSF) to hCSF. This indicates that hCSF possesses properties that are not matched by the aCSF, which is generally used for most electrophysiological recordings. To evaluate the possible significance of using hCSF as an electrophysiological recording medium, also for human brain tissue, we compared the network and single-cell firing properties of human brain slice cultures during perfusion with hCSF and aCSF. For measuring the overall activity from a majority of neurons within neocortical and hippocampal human slices, we used a microelectrode array (MEA) recording technique with 252 electrodes covering an area of 3.2 × 3.2 mm<sup>2</sup>. A second CMOS-based MEA with 4225 sensors on a 2 × 2 mm<sup>2</sup> area was used for detailed mapping of action potential waveforms and cell identification. We found that hCSF increased the number of active electrodes and neurons and the firing rate of the neurons in the slices and induced an increase in the numbers of single channel and population bursts. Interestingly, not only an increase in the overall activity in the slices was observed, but a reconfiguration of the network could also be detected with specific activation and inactivation of subpopulations of neuronal ensembles. In conclusion, hCSF is an important component to consider for future human brain slice studies, especially for experiments designed to mimic parts of physiology and disease observed <i>in vivo</i>.
Buried in water, burdened by nature—Resilience carried the Iron Age people through Fimbulvinter
2020-04-21

Levänluhta is a unique archaeological site with the remains of nearly a hundred Iron Age individuals found from a water burial in Ostrobothnia, Finland. The strongest climatic downturn of the Common Era, resembling the great Fimbulvinter in Norse mythology, hit these people during the 6th century AD. This study establishes chronological, dietary, and livelihood synthesis on this population based on stable carbon and nitrogen isotopic and radiocarbon analyses on human remains, supported by multidisciplinary evidence. Extraordinarily broad stable isotopic distribution is observed, indicating three subgroups with distinct dietary habits spanning four centuries. This emphasizes the versatile livelihoods practiced at this boundary of marine, freshwater, and terrestrial ecosystems. While the impact of the prolonged cold darkness of the 6th century was devastating for European communities relying on cultivation, the broad range of livelihoods provided resilience for the Levänluhta people to overcome the abrupt climatic decline.
Long-Term Isotope Evidence on the Diet and Habitat Breadth of Pleistocene to Holocene Caprines in Thailand: Implications for the Extirpation and Conservation of Himalayan Gorals
2020-04-21

Three taxa within the subfamily Caprinae (Himalayan goral Naemorhedus goral, Chinese goral Naemorhedus griseus, and Sumatran serow Capricornis sumatraensis) live in the mountainous upland forests of Southeast Asia, where they are considered as vulnerable or near threatened species. Co-occurrences between these two recognized genera have been documented from some Pleistocene fossil sites in Thailand, suggesting more widely overlapping distribution in the past than today. However, diet and habitat preferences of these Pleistocene and present-day coexisting species have rarely been investigated so far. For the past three decades, stable carbon and oxygen isotope analyses become more commonplace in ecological investigations, allowing us to explore the diets and habitats of ancient and extant animals as well as to reconstruct environmental conditions in the past. We reconstructed diets and habitats of these taxa from five fossil sites in Thailand during the past 400,000 years (from the Middle Pleistocene to the Early Holocene) and from some modern wildlife using the isotopic analysis of carbonate in tooth enamel, in order to test species co-occurrence patterns during the Pleistocene and to examine possible changes of their niche breadths over evolutionary time. Our carbon isotope analysis revealed remarkably different ecological patterns between Naemorhedus and Capricornis. The Pleistocene Sumatran serow has been a greater generalist than both the Himalayan and Chinese gorals that fed on pure C4 or mixed C3 and C4 plants restricted to an open landscape habitat and than its extant population that occupies a closed-canopy forest. This suggests that the habitat contraction of the modern wildlife is likely due to the Holocene climate change and the human impacts on Thai ecosystems. In addition to the loss or reduction of grasslands after the latest Pleistocene when rainforests became dominant and besides the human hunting and predation pressure, the high interspecific competition likely contributed to the extirpation of Himalayan gorals in Thailand. Developing a strategic plan for the future biodiversity conservation, a long-term historical isotope approach allowed us to predict the contrasting habitat suitability, a lowland grassland, for these two threatened goral species as testified by their ecological persistence during the Pleistocene.
A fungal member of theArabidopsis thalianaphyllosphere antagonizesAlbugo laibachiivia a secreted lysozyme
2020-04-21

Abstract Plants are not only challenged by pathogenic organisms, but also colonized by commensal microbes. The network of interactions these microbes establish with their host and amongst each other is suggested to contribute to the immune responses of plants against pathogens. In wild Arabidopsis thaliana populations, the oomycete pathogen Albugo laibachii has been shown to play an influential role in structuring the leaf phyllosphere. We show that the epiphytic yeast Moesziomyces bullatus ex Albugo on Arabidopsis, a close relative of pathogenic smut fungi, is an antagonistic member of the A. thaliana phyllosphere, which reduces infection of A. thaliana by A. laibachii . Combination of transcriptome analysis, reverse genetics and protein characterization identified a GH25 hydrolase with lysozyme activity as the major effector of this microbial antagonism. Our findings broaden the understanding of microbial interactions within the phyllosphere, provide insights into the evolution of epiphytic basidiomycete yeasts and pave the way for the development of novel biocontrol strategies.
Paralytic Agents for Intubation in the Out-of-Hospital Setting
2020-04-21

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Faculty Opinions recommendation of Mapping Host-Related Correlates of Influenza Vaccine-Induced Immune Response: An Umbrella Review of the Available Systematic Reviews and Meta-Analyses.
2020-04-21

Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact.Annual immunization is the most efficient way to reduce this burden.Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness.Influenza vaccine-induced immunogenicity is a function of host-, virus-and vaccine-related factors.Host-related factors constitute the most heterogeneous group.The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity.An umbrella review approach was undertaken.A total of 28 systematic reviews/meta-analyses were analyzed-these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette-Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression.In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out.The meta-analysis was conducted separately on each health condition category and virus (sub)type.A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map.The principal public health implications are discussed.
Faculty Opinions recommendation of Effect of annual influenza vaccination on reducing lung cancer in patients with chronic obstructive pulmonary disease from a population-based cohort study.
2020-04-21

Chronic obstructive pulmonary disease (COPD) patients are at a higher risk of development of lung cancer.Frequent exacerbations of COPD trigger the disease course to chronic inflammation which likely plays a role in the pathogenesis of lung cancer.Previous studies showed influenza virus infection is one of important causes for exacerbations of COPD.Therefore, the aim of this study was to know whether influenza vaccination could reduce the incidence of lung cancer in patients with COPD.This cohort study enrolled patients (≥55 years old) with a recorded diagnosis of COPD between January 1, 2000 and December 31, 2012 by using the Taiwan Health Insurance Database.A propensity score was calculated to reduce vaccine therapy selection bias.Cox proportional hazard regressions were used to investigate the association between the influenza vaccination and lung cancer incidence after adjusting for known confounding factors.Besides, we categorized the patients into 4 groups according to vaccination status (unvaccinated, total number of vaccinations: 1, 2-3, ≥4) to evaluate the dose-dependent effect on reducing lung cancer occurrence of lung cancer in COPD patients.Our study comprised of 28,752 eligible individuals from the COPD cohort database.Among them, 51% (14,630) received influenza vaccination; the rest (49%) of the COPD patients did not receive influenza vaccination.We observed that COPD patients receiving influenza vaccination had a lower risk of lung cancer (adjusted HR = 0.40, 95% CI (0.35-0.45),P < .001).We also founded comparable protective effect in both sexes and all age groups (55-64, 65-74, ≥75) regardless of influenza seasonality.Furthermore, dose-dependent protective effect could be seen after stratifying patients according to the total number vaccinations, the adjusted HRs for lung cancer risk were 0.48 (0.40-0.54) and 0.24 (0.20-0.29) for patients who received 2 to 3 and ≥4 vaccinations during the follow-up period.This population-based cohort study demonstrated that annual influenza vaccination administration could reduce incidence of lung cancer in COPD patients.
Faculty Opinions recommendation of A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities.
2020-04-21

BackgroundThe elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities.A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) while split virion vaccines elicit mostly antibodies.Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span. Materials and methodsOld (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS.Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays.Influenza-specific splenocyte CD4 + & CD8 + T cell responses were measured by flow cytometry.Full body computed tomography (CT) and structured necropsies were performed on day 42.Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores �5 were considered to have important comorbidities. ResultsOverall, 53.3% of the animals had significant comorbidities.Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03).Both CD4 + (TNFα, IFNγ) and CD8 + (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.
Faculty Opinions recommendation of Prime-pull vaccination with a plant-derived virus-like particle influenza vaccine elicits a broad immune response and protects aged mice from death and frailty after challenge.
2020-04-21

Background: Administered intramuscularly (IM), plant-derived, virus-like-particle (VLP) vaccines based on the influenza hemagglutinin (HA) protein elicit both humoral and cellular responses that can protect aged mice from lethal challenge.Unlike split virus vaccines, VLPs can be administered by different routes including intranasally (IN).We evaluated novel vaccine strategies such as prime-pull (IM boosted by IN) and multi-modality vaccination (IM and IN given simultaneously).We wished to determine if these approaches would provide better quality protection in old mice after less severe (borderline-lethal) challenge (ie: immunogenicity, frailty and survival).Results: Survival rates were similar in all vaccinated groups.Antibody responses were modest in all groups but tended to be higher in VLP groups compared to inactivated influenza vaccine (IIV) recipients.All VLP groups had higher splenocyte T cell responses than the split virus group.Lung homogenate chemokine/cytokine levels and virus loads were lower in the VLP groups compared to IIV recipients 3 days after challenge (p < 0.05 for viral load vs all VLP groups combined).The VLP-vaccinated groups also had less weight loss and recovered more rapidly than the IIV recipients.There was limited evidence of an immunologic or survival advantage with IN delivery of the VLP vaccine.Conclusion: Compared to IIV, the plant-derived VLP vaccine induced a broader immune response in aged mice (cellular and humoral) using either traditional (IM/IM) or novel schedules (multi-modality, prime-pull).