Inflammation and fibrosis in chronic liver diseases including non-alcoholic fatty liver disease and hepatitis C

At present chronic liver disease (CLD), the third commonest cause of premature death in the United Kingdom is detected late, when interventions are ineffective, resulting in considerable morbidity and mortality. Injury to the liver, the largest solid organ in the body, leads to a cascade of inflammatory events. Chronic inflammation leads to the activation of hepatic stellate cells that undergo trans-differentiation to become myofibroblasts, the main extra-cellular matrix producing cells in the liver; over time increased extra-cellular matrix production results in the formation of liver fibrosis. Although fibrogenesis may be viewed as having evolved as a “wound healing” process that preserves tissue integrity, sustained chronic fibrosis can become pathogenic culminating in CLD, cirrhosis and its associated complications. As the reference standard for detecting liver fibrosis, liver biopsy, is invasive and has an associated morbidity, the diagnostic assessment of CLD by non-invasive testing is attractive. Accordingly, in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice. Due to differing disease prevalence and treatment efficacy, disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection. To facilitate this, a review of the pathogenesis of both conditions is also conducted. Finally, the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed, including the current use of antifibrotic therapy

The DistilBERT Model: A Promising Approach to Improve Machine Reading Comprehension Models

Machine Reading Comprehension (MRC) is a challenging task in the field of Natural Language Processing (NLP), where a machine is required to read a given text passage and answer a set of questions based on it. This paper provides an overview of recent advances in MRC and highlights some of the key challenges and future directions of this research area. It also evaluates the performance of several baseline models on the dataset, evaluates the challenges that the dataset poses for existing MRC models, and introduces the DistilBERT model to improve the accuracy of the answer extraction process. The supervised paradigm for training machine reading and comprehension models represents a practical path forward for creating comprehensive natural language understanding systems. To enhance the DistilBERT basic model's functionality, we have experimented with a variety of question heads that differ in the number of layers, activation function, and general structure. DistilBERT is a model for question-resolution tasks that is successful and delivers state-of-the-art performance while requiring less computational resources than large models like BERT, according to the presented technique. We could enhance the model's functionality and obtain a better understanding of how the model functions by investigating other question head architectures. These findings could serve as a foundation for future study on how to make question-and-answer systems and other tasks connected to the processing of natural languages. &nbsp

Global analysis of atmospheric transmissivity using cloud cover, aridity and flux network datasets

Atmospheric transmissivity (t) is a critical factor in climatology, which affects surface energy balance, measured at a limited number of meteorological stations worldwide. With the limited availability of meteorological datasets in remote areas across different climatic regions, estimation of t is becoming a challenging task for adequate hydrological, climatic, and crop modeling studies. The availability of solar radiation data is comparatively less accessible on a global scale than the temperature and precipitation datasets, which makes it necessary to develop methods to estimate t. Most of the previous studies provided region specific datasets of t, which usually provide local assessments. Hence, there is a necessity to give the empirical models for t estimation on a global scale that can be easily assessed. This study presents the analysis of the t relationship with varying geographic features and climatic factors like latitude, aridity index, cloud cover, precipitation, temperature, diurnal temperature range, and elevation. In addition to these factors, the applicability of these relationships was evaluated for different climate types. Thus, empirical models have been proposed for each climate type to estimate t by using the most effective factors such as cloud cover and aridity index. The cloud cover is an important yet often overlooked factor that can be used to determine the global atmospheric transmissivity. The empirical relationship and statistical indicator provided the best performance in equatorial climates as the coefficient of determination (r2) was 0.88 relatively higher than the warm temperate (r2 = 0.74) and arid regions (r2 = 0.46). According to the results, it is believed that the analysis presented in this work is applicable for estimating the t in different ecosystems across the globe

Holographic dilepton production in a thermalizing plasma

We determine the out-of-equilibrium production rate of dileptons at rest in strongly coupled N=4 Super Yang-Mills plasma using the AdS/CFT correspondence. Thermalization is achieved via the gravitational collapse of a thin shell of matter in AdS_5 space and the subsequent formation of a black hole, which we describe in a quasistatic approximation. Prior to thermalization, the dilepton spectral function is observed to oscillate as a function of frequency, but the amplitude of the oscillations decreases when thermal equilibrium is approached. At the same time, we follow the flow of the quasinormal spectrum of the corresponding U(1) vector field towards its equilibrium limit.Comment: 21 pages, 7 figures. v2: Version accepted for publication in JHEP; minor modifications, added reference

Are village health sanitation and nutrition committees fulfilling their roles for decentralised health planning and action? A mixed methods study from rural eastern India.

BACKGROUND: In India, Village Health Sanitation and Nutrition Committees (VHSNCs) are participatory community health forums, but there is little information about their composition, functioning and effectiveness. Our study examined VHSNCs as enablers of participatory action for community health in two rural districts in two states of eastern India - West Singhbhum in Jharkhand and Kendujhar, in Odisha. METHODS: We conducted a cross-sectional survey of 169 VHSNCs and ten qualitative focus group discussions with purposively selected better and poorer performing committees, across the two states. We analysed the quantitative data using descriptive statistics and the qualitative data using a Framework approach. RESULTS: We found that VHSNCs comprised equitable representation from vulnerable groups when they were formed. More than 75 % members were women. Almost all members belonged to socially disadvantaged classes. Less than 1 % members had received any training. Supervision of committees by district or block officials was rare. Their work focused largely on strengthening village sanitation, conducting health awareness activities, and supporting medical treatment for ill or malnourished children and pregnant mothers. In reality, 62 % committees monitored community health workers, 6.5 % checked sub-centres and 2.4 % monitored drug availability with community health workers. Virtually none monitored data on malnutrition. Community health and nutrition workers acted as conveners and record keepers. Links with the community involved awareness generation and community monitoring of VHSNC activities. Key challenges included irregular meetings, members' limited understanding of their roles and responsibilities, restrictions on planning and fund utilisation, and weak linkages with the broader health system. CONCLUSIONS: Our study suggests that VHSNCs perform few of their specified functions for decentralized planning and action. If VHSNCs are to be instrumental in improving community health, sanitation and nutrition, they need education, mobilisation and monitoring for formal links with the wider health system

Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus : studies in the pig model of influenza

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs

Extreme rainfall events alter the trophic structure in bromeliad tanks across the Neotropics

Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics

Climate influences the response of community functional traits to local conditions in bromeliad invertebrate communities

Functional traits determine an organism's performance in a given environment and as such determine which organisms will be found where. Species respond to local conditions, but also to larger scale gradients, such as climate. Trait ecology links these responses of species to community composition and species distributions. Yet, we often do not know which environmental gradients are most important in determining community trait composition at either local or biogeographical scales, or their interaction. Here we quantify the relative contribution of local and climatic conditions to the structure and composition of functional traits found within bromeliad invertebrate communities. We conclude that climate explains more variation in invertebrate trait composition within bromeliads than does local conditions. Importantly, climate mediated the response of traits to local conditions; for example, invertebrates with benthic life‐history traits increased with bromeliad water volume only under certain precipitation regimes. Our ability to detect this and other patterns hinged on the compilation of multiple fine‐grained datasets, allowing us to contrast the effect of climate versus local conditions. We suggest that, in addition to sampling communities at local scales, we need to aggregate studies that span large ranges in climate variation in order to fully understand trait filtering at local, regional and global scales

Baroreflex sensitivity is impaired in survivors of mild COVID-19 at 3-6 months of clinical recovery; association with carotid artery stiffness

The association between the stiffening of barosensitive regions of central arteries and the derangements in baroreflex functions remains unexplored in COVID-19 survivors. Fifty-seven survivors of mild COVID-19 (defined as presence of upper respiratory tract symptoms and/or fever without shortness of breath or hypoxia; SpO2 > 93%), with an age range of 22-66 years (27 females) participated at 3-6 months of recovering from the acute phase of RT-PCR positive COVID-19. Healthy volunteers whose baroreflex sensitivity (BRS) and arterial stiffness data were acquired prior to the onset of the pandemic constituted the control group. BRS was found to be significantly lower in the COVID survivor group for the systolic blood pressure-based sequences (BRS SBP ) [9.78 (7.16-17.74) ms/mmHg vs 16.5 (11.25-23.78) ms/mmHg; p = 0.0253]. The COVID survivor group showed significantly higher carotid β stiffness index [7.16 (5.75-8.18) vs 5.64 (4.34-6.96); (p = 0.0004)], and pulse wave velocity β (PWVβ ) [5.67 (4.96-6.32) m/s vs 5.12 (4.37-5.41) m/s; p = 0.0002]. BRS quantified by both the sequence and spectral methods showed an inverse correlation with PWVβ in the male survivors. Impairment of BRS in the male survivors of mild COVID-19 at 3-6 months of clinical recovery shows association with carotid artery stiffness