Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Methylation and Immune Cell Markers Demonstrate Evidence of Accelerated Aging in Patients with Chronic Hepatitis B Virus or Hepatitis C Virus, with or without Human Immunodeficienct Virus Co-infection

Background. Several chronic diseases accelerate biological aging. We investigated age acceleration and the association between peripheral blood DNA methylation (DNAm) and immune cell markers in patients chronically infected with the hepatitis B virus (HBV) or the hepatitis C virus (HCV) with and without human immunodeficiency virus (HIV) co-infection. Methods. Age acceleration was measured as the difference between epigenetic age (Horvath clock) and chronological age. The immune marker model of age acceleration was developed using Elastic Net regression to select both the immune markers and their associated weights in the final linear model. Results. Patients with chronic HBV (n = 51) had a significantly higher median epigenetic age compared to chronological age (age accelerated) ( P < .001). In patients with chronic HCV infection (n = 63), age acceleration was associated with liver fibrosis as assessed by histology ( P < .05), or presence of HIV co-infection ( P < .05), but not HCV mono-infection. Age acceleration defined by immune markers was concordant with age acceleration by DNA methylation (correlation coefficient = .59 in HBV; P = .0025). One-year treatment of HBV patients with nucleoside therapy was associated with a modest reduction in age acceleration, as measured using the immune marker model (−.65 years, P = .018). Conclusion. Our findings suggest that patients with chronic viral hepatitis have accelerated epigenetic aging, that immune markers define biological age, and have the potential to assess the effects of therapeutic intervention on age acceleration.
Evidence of a large, international network of international hepatitis C virus transmission in HIV-positive men who have sex with men

Background— Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in HIV-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM. Methods— HIV-positive MSM diagnosed with recent HCV (n=226) enrolled into a molecular phylogenetic study. Using real-time PCR, the NS5B region of the HCV genome (436 bp) was amplified, sequenced and compared with unrelated NS5B sequences. Results— NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%); 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value >70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; p=0.03). ‘Molecular clock’ analysis indicated that the majority (85%) of transmissions occurred since 1996. Discussion— Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries; the low evolutionary distances among HCV isolates from different countries; and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active anti-retroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.
Regulation of Skeletal Muscle Tension Redevelopment by Troponin C Constructs with Different Ca 2 1 Affinities

In maximally activated skinned fibers, the rate of tension redevelopment ( k tr ) following a rapid release and restretch is determined by the maximal rate of cross-bridge cycling. During submaximal Ca 2 1 activations, however, k tr regulation varies with thin filament dynamics. Thus, decreasing the rate of Ca 2 1 dissociation from TnC produces a higher k tr value at a given tension level (P), especially in the [Ca 2 1 ] range that yields less than 50% of maximal tension (P o ). In this study, native rabbit TnC was replaced with chicken recombinant TnC, either wild-type (rTnC) or mutant (NHdel), with decreased Ca 2 1 affinity and an increased Ca 2 1 dissociation rate ( k off ). Despite marked differences in Ca 2 1 sensitivity ( . 0.5 D pCa 50 ), fibers reconstituted with either of the recombinant proteins exhibited similar k tr versus tension profiles, with k tr low (1–2 s 2 1 ) and constant up to ; 50% P o , then rising sharply to a maximum (16 6 0.8 s 2 1 ) in fully activated fibers. This behavior is predicted by a four-state model based on coupling between cross-bridge cycling and thin filament regulation, where Ca 2 1 directly affects only individual thin filament regulatory units. These data and model simulations confirm that the range of k tr values obtained with varying Ca 2 1 can be regulated by a rate-limiting thin filament process.
Infant birth size and early infant pneumonia predict linear growth faltering among HIV-exposed uninfected infants in Kenya.

INTRODUCTION Stunting remains a global health priority, particularly in sub-Saharan Africa. Identifying determinants of linear growth in HIV-exposed uninfected (HEU) infants can inform interventions to prevent stunting in this vulnerable population. METHODS HIV-infected mothers and their uninfected infants were followed monthly from pregnancy to 12 months postpartum in Nairobi, Kenya. Mixed-effects models estimated the change in length-for-age z-score (LAZ) from birth to 12 months by environmental, maternal, and infant characteristics. Multivariable models included factors univariately associated with LAZ. RESULTS Among 372 HEU infants, mean LAZ decreased from -0.54 (95% confidence interval [CI]: -0.67, -0.41) to -1.09 (95% CI: -1.23, -0.96) between 0-12 months. Declines in LAZ were associated with crowding (≥2 persons/room; adjusted difference in 0-12 month change [AD]: -0.46; 95% CI: -0.87, -0.05), use of a pit latrine versus a flush toilet (AD: -0.29; 95% CI: -0.57, -0.02), and early infant pneumonia (AD: -1.14; 95% CI: -1.99, -0.29). Infants with low birthweight (<2500g; AD 1.08: 95% CI: 0.40, 1.76) and birth stunting (AD: 1.11; 95% CI: 0.45, 1.78) experienced improved linear growth. By 12 months of age, 46 infants were stunted, of whom 11 (24%) were stunted at birth. Of the 34 infants stunted at birth, with an available 12-month LAZ, 68% were not stunted at 12 months. CONCLUSIONS Some low birthweight and birth stunted HEU infants had significant linear growth recovery. Early infant pneumonia and household environment predicted poor linear growth and may identify a subgroup of HEU infants for whom to provide growth-promoting interventions.
Final report of IEA Task 29, Mexnext (Phase 1): Analysis of Mexico wind tunnel measurements

This report describes the work performed within the first phase of IEA Task 29 Mexnext. In this IEA Task 29 a total of 20 organisations from 11 different countries collaborated in analysing the measurements which have been taken in the EU project ‘Mexico’. Within this Mexico project 9 European institutes carried out a wind tunnel experiment in the Large Low Speed Facility (LLF) of the German Dutch Wind Facilities DNW on a rotor with a diameter of 4.5 m. Pressure distributions were measured at five location along the blade along with detailed flow field measurements around the rotor plane using stereo PIV. The following organisations (and persons) cooperated in the projects: • Canada: École de technologie supérieur, Montréal, ETS (C. Masson, S. Breton, C. Sibuet), and University of Victoria, UVIC (C. Crawford) • Denmark: RISØ-DTU (H. Madsen, N. Sørensen, P. Rethouré) and the Technical University of Denmark DTU-MEK (W. Z. Shen) • Germany: University of Stuttgart, Ustutt (T. Lutz, K. Meister), University of Applied Sciences at Kiel/CEWind EG (P. Schaffarczyk and A. Jeromin), ForWind (B. Stoevesandt and I. Hernandez) • Israel: Technion, Israel Institute of Technology (A. Rosen, V. Ognev. R. Gordon) • Japan: Mie University/National Institute of Advanced Industrial Science (T. Maeda, Y. Kamada, J. Murata) • Korea: Korea Institute of Energy Research KIER, (H. Shin) and Korea Aerospace Research Institute, KARI (C. Kim, T. Cho) • Netherlands: Energy Research Center of the Netherlands, ECN (G. Schepers, K. Boorsma, H. Snel), Delft University of Technology, TUDelft (G. van Bussel, N. Timmer, D. Micallef), Suzlon Blade Technology, SBT (A. Verhoeff), Technical University of Twente, TUTwente (E. van der Weide) • Norway: Institute for Energy Technology/Norwegian University of Science and Technology, IFE (A. Knauer, J. van Rij) • Spain: National Renewable Energy Center, CENER (X. Munduate, S. Gomez-Iradi, A. Gonzalez, A. Irisarri) and National Institute for Aerospace Technology, INTA (C. Redondo Calle) • Sweden: Royal Institute of Technology/University of Gotland, KTH/HGO (S. Ivanell and K. Nilsson) • USA: National Renewable Energy Laboratory, NREL (S. Schreck) The Energy Research Center of the Netherlands, ECN acted as Operating Agent. As a result of the international collaboration within this task a very thorough analysis of the data could be carried out and a large number of codes were validated not only in terms of loads but also in terms of underlying flow field. The detailed pressure measurements along the blade in combination with the detailed flow field measurements gave a unique opportunity to better understand the response of a wind turbine to the incoming flow field. Deficiencies in modelling have been established and directions for model improvement could be given.
Altered Functional Brain Network Integration, Segregation and Modularity in Very Preterm Infants at Term Equivalent Age

Objectives: To determine the functional network organization of the brain in infants born very preterm at term equivalent age and to relate network alterations to known clinical risk factors for poor neurologic outcomes in prematurity. Study design: Resting state functional MRI data from 66 VPT infants (gestational age < 32wks and birth weight <1500g) and 66 healthy full term neonates, acquired as part of a prospective, cross-sectional study, were compared at term age using graph theory. Features of resting state networks, including integration, segregation and modularity, were derived from correlated hemodynamic activity arising from 93 cortical and subcortical regions of interest and compared between groups. Results: Despite preserved small world topology and modular organization, resting state networks of VPT infants at TEA were less segregated and less integrated than those of full term infants. Chronic respiratory illness (ie, bronchopulmonary dysplasia and the length of oxygen support) was associated with decreased global efficiency and increased path lengths (p-value < 0.05). In both cohorts, four functional modules with similar composition were observed (parietal/ temporal, frontal, subcortical/limbic and occipital). The density of connections in three out of the four modules was decreased in the VPT network (P value < .01), however in the occipital/visual cortex module, connectivity was increased in VPT relative to controls (p-value < 0.0001).
Exposure of Neurons to Excitotoxic Levels of Glutamate Induces Cleavage of ADAR2 and Loss of GluR2 Editing

AMPA receptors are glutamate receptors that are tetramers of various combinations of GluR1-4 subunits. AMPA receptors containing GluR1, 3 and 4 are Ca 2+ permeable, however, AMPA receptors containing even a single subunit of GluR2 are Ca 2+ impermeable. Most AMPA receptors are Ca 2+ impermeable due to the presence of GluR2. GluR2 confers special properties on AMPA receptors through the presence of arginine at the pore apex; other subunits (GluR1, 3, 4) contain glutamine at the pore apex and allow Ca 2+ influx. Normally, an RNA editing step changes DNA-encoded glutamine to arginine, introduces arginine in the GluR2 pore apex. GluR2 RNA editing is carried out by an RNA-dependent adenosine deaminase (ADAR2). Loss of GluR2 editing leads to the formation of highly excitotoxic AMPA channels (Mahajan and Ziff, 2007) and is shown to contribute to loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS). Relatively higher levels of Ca 2+ permeable AMPA receptors are found in motor neurons and this has been correlated with lower GluR2 mRNA levels. However, the reason for loss of GluR2 editing is not known. Here we show that exposure of neurons to excitotoxic levels of glutamate leads to specific cleavage of ADAR2 that leads to generation of unedited GluR2. We demonstrate that cleaved ADAR2 leads to decrease or loss of GluR2 editing, which will further result in high Ca 2+ influx and excitotoxic neuronal death.
Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF

: The preimplantation stage of development is exquisitely sensitive to environmental stresses, and changes occurring during this developmental phase may have long-term health effects. Animal studies indicate that IVF offspring display metabolic alterations, including hypertension, glucose intolerance and cardiac hypertrophy, often in a sexual dimorphic fashion. The detailed nature of epigenetic changes following in-vitro culture is, however, unknown. This study was performed to evaluate the epigenetic (using whole-genome bisulﬁte sequencing (WGBS) and assay for transposase-accessible chromatin using sequencing (ATAC-seq)) and transcriptomic changes (using RNA-seq) occurring in the inner cell mass (ICM) of male or female mouse embryos generated in vivo or by IVF. We found that the ICM of IVF embryos, compared to the in-vivo ICM, differed in 3% of differentially methylated regions (DMRs), of which 0.1% were located on CpG islands. ATAC-seq revealed that 293 regions were more accessible and 101 were less accessible in IVF embryos, while RNA-seq revealed that 21 genes were differentially regulated in IVF embryos. Functional enrichment analysis revealed that stress signalling (STAT and NF-kB signalling), developmental processes and cardiac hypertrophy signalling showed consistent changes in WGBS and ATAC-seq platforms. In contrast, male and female embryos showed minimal changes. Male ICM had an increased number of signiﬁcantly hyper-methylated DMRs, while only 27 regions showed different chromatin accessibility and only one gene was differentially expressed. In summary, this study provides the ﬁrst comprehensive analysis of DNA methylation, chromatin accessibility and RNA expression changes induced by IVF in male and female ICMs. This dataset can be of value to all researchers interested in the developmental origin of health and disease (DOHaD) hypothesis and might lead to a better understanding of how early embryonic manipulation may affect adult health.
Seasonal Variation of Organogenetic Activity and Reserves Allocation in the Shoot Apex of Pinus pinaster Ait.

d Background and aims To understand better the basic growth characteristics of pines and the fundamental prop- erties of the shoot apical meristem (SAM), variations within the shoot apex of buds were studied. d Methods A detailed structural comparison of meristem dimensions, organogenetic activity, and the presence of lipids, starch grains and tannins was performed on shoot apices of juvenile, and male and female adult Pinus pinaster at ﬁve different times in the annual growth cycle. d Key results There were signiﬁcant correlations among traits and differences in the pattern for juvenile and adult shoots. In juvenile shoots, peaks of organogenesis were present in spring and autumn, but not in summer. In adult shoots, one peak, characterized by an increase in meristem dimensions, was present in summer. The accumulation of starch grains beneath the SAM and of tannin in sub-apical pith parenchyma were at their maximum when organogenetic activity was high in spring and autumn in juvenile plants, and in summer in adult plants. In juvenile and adult plants, lipids were stored within the SAM in autumn, ﬁlling a large part of the bud in winter, and were depleted in the cortical parenchyma and then in the pith during shoot elongation. d Conclusions Depending on the sites of accumulation within the SAM and on the stage of the annual growth cycle, lipids, starch and tannins may be involved in different processes. In spring, energy and structural materials released by lipid hydrolysis may contribute to stem elongation and/or cell-to-cell communication. During orga- nogenesis, energy and structural materials released by starch hydrolysis may inﬂuence developmental programmes in the SAM and adjacent cells. Tannins may be involved in cellular detoxiﬁcation. At the end of the growing season, accumulation of lipid and starch is positively correlated with the onset of dormancy.
Moving the Needle on Clostridioides difficile Research in Children: A Major Step Forward but Challenges Remain

EDITORIAL COMMENTARY • cid 2020:71 (15 November) • 2589 Received 2 November 2019; editorial decision 20 November 2019; accepted 25 November 2019; published online November 27, 2019. Correspondence: L. K. Kociolek, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue, Box 205, Chicago, IL 60611-2605 (lkociolek@luriechildrens.org). Clinical Infectious Diseases 2020;71(10):2589–91 © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciz1154 Moving the Needle on Clostridioides difficile Research in Children: A Major Step Forward but Challenges Remain
Large‐Scale Afforestation Enhances Precipitation by Intensifying the Atmospheric Water Cycle Over the Chinese Loess Plateau

Afforestation is an appropriate approach to control soil erosion, but consumes extra water resources. It also exerts feedbacks on local precipitation, affecting the water availability for water‐limited areas. The Chinese Loess Plateau (LP) has implemented the world's largest afforestation program to mitigate severe soil erosion. However, it remains unclear how the atmospheric water cycle responds to large‐scale afforestation under climate change. Here we show that afforestation elevates precipitation in rainy season by intensifying the atmospheric water cycle over the LP. Results show the upward trend of vegetation coverage fraction increased by 3.15% decade−1 and climatological precipitation increased by 54.62 mm after launching the large‐scale afforestation in 1999. Such afforestation also enhanced evapotranspiration by 22.56 mm. We found the moisture inflow and outflow continuously decreased, but more atmospheric moisture was retained since the rate of decline of inflow was less than that of outflow. Using a dynamic precipitation recycling method, we explored changes in precipitation recycling and components of the atmospheric water budget. The precipitation recycling ratio increased from 9.16 ± 0.35 to 10.18 ± 0.28% after the afforestation. Both external and internal branches of the atmospheric water cycle have been strengthened, and their contributions to the increased precipitation are 84.93% and 15.07%, respectively. The afforestation caused a more humid atmosphere, heightened soil moisture‐vegetation‐precipitation feedback, stronger moisture convergence, and more clouds; these changes favored precipitation generation. This study advances the understanding of how afforestation affects regional climate from a precipitation recycling perspective, further assisting decision‐makers to establish sustainable afforestation strategies.
Capacity investment and the value of operational flexibility in manufacturing systems with product blending

A distinct feature of process industries such as food, chemical and consumer packaged goods is the blending of intermediates into finished goods. In the context of such manufacturing systems the levels of different inputs that can be blended to process a final good define the range of flexibility. Likewise, the cost for using (blending) different inputs defines the mobility element of flexibility. In this paper, we investigate capacity investment and the value of flexibility in the presence of such product blending constraints. We are motivated by recent case studies of food manufacturers, in particular, those manufacturers that seek to increase flexibility via blending of intermediates. We analyse stochastic programs under demand uncertainty of such manufacturing systems. We provide analytical insights into trade-offs when range and mobility are interdependent. Our analytical work gives structural insights into subtle complementarity and substitution effects between dedicated and shared resources in the presence of blending. We analytically show that there is a degradation in the cost performance of such systems with an increase in correlation. We characterise the optimal blending fraction that balances the benefits of higher range with higher costs (lower mobility). Our numerical work shows that a moderate level of blending can significantly improve flexibility and that well-known guidelines for designing limited flexibility change in the presence of blending. For example, blending, even if optimally designed, weakens the appeal of chaining configurations. Overall our work guides resource configuration in industries where product blending is an integral part of the production process.
18F-FDG PET/CT as Predictive of Response after Chemoradiation in Esophageal Cancer Patients

Introduction— The purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18F-FDGPET/CT studies could provide information on pathologic response to CTRT and overall survival (OS). manuscript copyediting, typesetting, review of the proof the production process errors may be content, legal disclaimers Materials and Methods— Thirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12+/-2 days after onset of CTRT) and a post-CTRT 18F-FDGPET/CT study. The 18F-FDGPET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). Clinical and 18F-FDGPET/CT parameters were correlated with pathologic complete response (pathCR) and OS. Results— Among the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% CI: 19.9 – NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p=0.06). None of the other variables was predictive of pCR. There was association between OS and baseline TLG (p=0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively). Conclusion— None of the PET parameters are predictive of pCR but TLG at baseline and post-CTRT are prognostic of OS.
Rotifer Diversity (Rotifera: Eurotatoria) of Floodplain Lakes of Pobitora Wild Life Sanctuary, Assam

Floodplain wetlands, an integral component of tropical riverine systems of the world, are known to be the richest habitats for the rotifer diversity (Segers et al., 1993; Sanoamuang, 1998; Sharma and Sharma, 2001; Sharma, 2005). Various wild life sanctuaries of North-Eastern India and that of the state of Assam are characterized by myriads of floodplain lakes (locally known as "beels") providing habitat par excellence for several wild animals as well as a wide array of vertebrates and invertebrates. However, no attention has so far been focused on the micro-faunal diversity of beels of sanctuaries of N. E. region in general and that of Rotifera in particular. The members of the later Phylum invariably comprise a dominant group of micro-invertebrate communities of these interesting ecotones and contribute significantly to their productivity.