bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-Days Reduction of Plasma and Skin Advanced Glycation End Products is Related to Outcome in Septic Patients
Authors: Rodriguez-Ruiz Emilio , Lopez-Lago Ana , Hernandez-Vaquero Rebeca , Granja-Gomez Isabel , Estany-Gestal Ana , Alvarez Ezequiel , Garcia-Gonzalez Miguel , Garcia-Allut Jose L. 
Published: June 2019

ABSTRACT

Background:
Advanced glycation end products (AGEs) are a result of nonenzymatic glycation of proteins and lipids, which can attach to either their cell surface receptor (RAGE) or its soluble form (sRAGE). Evidence exists for the implication of AGE-RAGE axis in sepsis, but data are still insufficient and conflicting. We aimed to analyze the kinetics of plasma and skin AGEs and sRAGE during sepsis, and their association with outcome in septic patients.

Methods:
We performed a prospective observational study. We enrolled 90 consecutive patients with severe sepsis or septic shock, within the first 24 h of Intensive Care Unit admission. During the first 5 days of sepsis, we measured plasma autofluorescence (PAF) and skin autofluorescence (SAF) as surrogates of circulating and skin AGEs, respectively. sRAGE was measured on days 1, 3, and 5. Delta values were defined as the difference between the PAF, SAF, or sRAGE on a specific day and the value on day 1.

Results:
28-day mortality was 18%. Bivariate analysis found that ΔPAF3-1, ΔPAF4-1, ΔPAF5-1, and ΔSAF5-1 were significantly associated with 28-day mortality. Additionally, sRAGE1 was inversely correlated to ΔPAF4-1 (r = −0.250, P = 0.019) and ΔPAF5-1 (r = −0.246, P = 0.024), and significantly associated with 28-day mortality. In an adjusted multivariate logistic regression analysis, ΔPAF2-1, ΔPAF3-1, ΔPAF4-1, ΔPAF5-1, and ΔSAF5-1 were associated with 28-day mortality.

Conclusions:
Kinetics of plasma and skin AGEs during the first days of sepsis are independently associated with mortality, where a decrease of plasma and skin AGEs are related to higher mortality.
Outcomes of an Overnight-Stay Unit for Urogynecologic Surgery: Feasibility and Risk Factors for Failure of Next-Day Discharge
Authors: Clancy Aisling A. , Ilin Julius , Pascali Dante , Shehata Fady , Hickling Duane R. 
Published: June 2019

Objective
To evaluate outcomes of patients undergoing urogynecologic procedures with postoperative care in an overnight-stay unit at a tertiary care center.

Methods
A retrospective cohort study of 1644 women admitted to an overnight-stay unit at a Canadian tertiary care center after urogynecologic surgery between 2014 and 2018 was completed. A multivariable logistic regression model was fit to identify risk factors for failed next-day discharge, defined as a delayed discharge of more than 24 hours, readmission within 30 days of surgery, or emergency room assessment within 7 days of surgery.

Results
One thousand five hundred seventy-eight patients (96%) were discharged within 24 hours of surgery. Mean patient age was 53.7 ± 15.1 years, with 21.2% 70 years or older. Surgical approaches included laparotomies (8.9%), major vaginal surgery (70.9%), and open retropubic procedures (2.1%). Hysterectomies were performed in 1120 patients (68.1%). One hundred one patients (6.1%) were assessed in the emergency department within 7 days of surgery, and 57 (3.5%) were readmitted to hospital within 30 days of their procedure. Multivariable regression identified the following as risk factors for failed next-day discharge: pulmonary disease (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.32–8.06; P = 0.010), longer operating time (OR, 1.40; 95% CI, 1.10–1.79; P = 0.006, per 60 minutes), and intraoperative hemorrhagic complications (OR, 22.64; 95% CI, 5.83–88.00, P < 0.001).

Conclusions
Admission to an overnight-stay unit with next-day discharge is feasible for most patients undergoing urogynecologic surgery. Factors associated with requiring a longer hospital stay, presentation to an emergency department, or readmission to hospital within 7 days include pulmonary disease, longer operating times, and intraoperative hemorrhagic complications.
Climate drivers of malaria at its southern fringe in the Americas
Authors: Laneri Karina , Cabella Brenno , Prado Paulo Inácio , Coutinho Renato Mendes , Kraenkel Roberto André 
Published: June 2019

AbstractIn this work we analyze potential environmental drivers of malaria cases in Northwestern Argentina. We inspect causal links between malaria and climatic variables by means of the convergent cross mapping technique, which provides a causality criterion from the theory of dynamic systems. Analysis is based on 12 years of weekly malaria P. vivax cases in Tartagal, Salta, Argentina—at the southern fringe of malaria incidence in the Americas—together with humidity and temperature time-series spanning the same period. Our results show that there are causal links between malaria cases and both maximum temperature, with a delay of five weeks, and minimum temperature, with delays of zero and twenty two weeks. Humidity is also a driver of malaria cases, with thirteen weeks delay between cause and effect. Furthermore we also determined the sign and strength of the effects. Temperature has always a positive non-linear effect on cases, with maximum temperature effects more pronounced above 25° C and minimum above 17° C, while effects of humidity are more intricate: maximum humidity above 85% has a negative effect, whereas minimum humidity has a positive effect on cases. These results might be signaling processes operating at short (below 5 weeks) and long (over 12 weeks) time delays, corresponding to effects related to parasite cycle and mosquito population dynamics respectively. The non-linearities found for the strength of the effect of temperature on malaria cases make warmer areas more prone to higher increases in the disease incidence. Moreover, our results indicate that an increase of extreme weather events could enhance the risks of malaria spreading and re-emergence beyond the current distribution. Both situations, warmer climate and increase of extreme events, will be remarkably increased by the end of the century in this hot spot of climate change.
The “creatures” of the human cortical somatosensory system
Authors: Saadon-Grosman N. , Loewenstein Y. , Arzy S. 
Published: June 2019

AbstractPenfield’s description of the “homunculus”, a “grotesque creature” with large lips and hands and small trunk and legs depicting the representation of body-parts within the primary somatosensory cortex (S1), is one of the most prominent contributions to the neurosciences. Since then, numerous studies have identified additional body-parts representations outside of S1. Nevertheless, it has been implicitly assumed that S1’s homunculus is representative of the entire somatosensory cortex. Therefore, the distribution of body-parts representations in other brain regions, the property that gave Penfield’s homunculus its famous “grotesque” appearance, has been overlooked. We used whole-body somatosensory stimulation, functional MRI and a new cortical parcellation to quantify the organization of the cortical somatosensory representation. Our analysis showed first, an extensive somatosensory response over the cortex; and second, that the proportional representation of body-parts differs substantially between major neuroanatomical regions and from S1, with, for instance, much larger trunk representation at higher brain regions, potentially in relation to the regions’ functional specialization. These results extend Penfield’s initial findings to the higher level of somatosensory processing and suggest a major role for somatosensation in human cognition.
Reliable confidence intervals for RelTime estimates of evolutionary divergence times
Authors: Tao Qiqing , Tamura Koichiro , Mello Beatriz , Kumar Sudhir 
Published: June 2019

AbstractConfidence intervals (CIs) depict the statistical uncertainty surrounding evolutionary divergence time estimates. They capture variance contributed by the finite number of sequences and sites used in the alignment, deviations of evolutionary rates from a strict molecular clock in a phylogeny, and uncertainty associated with clock calibrations. Reliable tests of biological hypotheses demand reliable CIs. However, current non-Bayesian methods may produce unreliable CIs because they do not incorporate rate variation among lineages and interactions among clock calibrations properly. Here, we present a new analytical method to calculate CIs of divergence times estimated using the RelTime method, along with an approach to utilize multiple calibration uncertainty densities in these analyses. Empirical data analyses showed that the new methods produce CIs that overlap with Bayesian highest posterior density (HPD) intervals. In the analysis of computer-simulated data, we found that RelTime CIs show excellent average coverage probabilities, i.e., the true time is contained within the CIs with a 95% probability. These developments will encourage broader use of computationally-efficient RelTime approach in molecular dating analyses and biological hypothesis testing.
Simple and complex interactions between sleep-wake driven and circadian processes shape daily genome regulatory dynamics in the mouse
Authors: Hor Charlotte N. , Yeung Jake , Jan Maxime , Emmenegger Yann , Hubbard Jeffrey , Xenarios Ioannis , Naef Felix , Franken Paul 
Published: June 2019

AbstractThe timing and duration of sleep results from the interaction between a sleep-wake driven, or homeostatic, process (S) and a circadian process (C), and involves changes in gene expression and genomic regulation. Unraveling the respective contributions of S and C, and their interaction, to transcriptional and epigenomic regulatory dynamics requires sampling over time under unperturbed conditions and conditions of perturbed sleep. Here, we profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a three-day period, including a 6-hour sleep deprivation (SD) on day two. Mathematical modeling established that a large proportion of rhythmic genes are actually governed by Process S with varying degrees of interaction with Process C, sometimes working in opposition. Remarkably, SD causes long-term effects on gene expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a dampening of the oscillation of most core clock genes, includingBmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Distal regions, rather than promoters, display dynamics corresponding to gene transcription, implying that changes in mRNA expression result from constantly accessible promoters under the influence of distal enhancers or repressors.Srfwas predicted as a transcriptional regulator driving immediate response, suggesting thatSrfactivity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level. Such effects might accumulate with repeated sleep restrictions, thereby contributing to their adverse health effects.Significance statementWhen and how long we sleep is determined by the time-of-day and how long we have been awake, which are tracked molecularly by a circadian and a sleep-wake driven process, respectively. We measured the long-term consequences of a short-term sleep deprivation (SD) on gene expression and regulation in the mouse brain, and used mathematical models to determine the relative contributions of the circadian and sleep-wake driven processes. We find that many genes, including most of the genes that constitute the molecular circadian clock, are perturbed by SD long after the mice ceased showing behavioral signs of sleep loss. Our results have implications for human health, given the high prevalence of insufficient and poor quality sleep in our contemporary society.
Enhancer-dependence of gene expression increases with developmental age
Authors: Cai Wenqing , Huang Jialiang , Zhu Qian , Li Bin E. , Seruggia Davide , Zhou Pingzhu , Nguyen Minh , Fujiwara Yuko , Xie Huafeng , Yang Zhenggang , Hong Danni , Ren Pengfei , Xu Jian , Pu William T. , Yuan Guo-Cheng , Orkin Stuart H. 
Published: June 2019

SummaryHow overall principles of gene regulation (the “logic”) may change during ontogeny is largely unexplored. We compared transcriptomic, epigenomic and topological profiles in embryonic (EryP) and adult (EryD) erythroblasts. Despite reduced chromatin accessibility compared to EryP, distal chromatin of EryD is enriched in H3K27ac, Gata1 and Myb occupancy. In contrast to EryP-specific genes, which exhibit promoter-centric regulation through Gata1, EryD-specific genes employ distal enhancers for long-range regulation through enhancer-promoter looping, confirmed by Gata1 HiChIP. Genome editing demonstrated distal enhancers are required for gene expression in EryD but not in EryP. Applying a metric for enhancer-dependence of transcription, we observed a progressive reliance on enhancer control with increasing age of ontogeny among diverse primary cells and tissues of mouse and human origin. Our findings highlight fundamental and conserved differences in regulatory logic at distinct developmental stages, characterized by simpler promoter-centric regulation in embryonic cells and combinatorial enhancer-driven control in adult cells.HighlightsRegulation of embryonic-specific erythroid genes is promoter-centric through Gata1Adult-specific control is combinatorial enhancer-driven and requires MybAdult specific genes have increased enhancer-promoter chromatin interactionsEnhancer-dependence increases progressively with increasing developmental age
Distinguishing coalescent models - which statistics matter most?
Authors: Freund Fabian , Siri-Jégousse Arno 
Published: June 2019

AbstractModelling genetic diversity needs an underlying genealogy model. To choose a fitting model based on genetic data, one can perform model selection between classes of genealogical trees, e.g. Kingman’s coalescent with exponential growth or multiple merger coalescents. Such selection can be based on many different statistics measuring genetic diversity. A random forest based Approximate Bayesian Computation is used to disentangle the effects of different statistics on distinguishing between various classes of genealogy models. For the specific question of inferring whether genealogies feature multiple mergers, a new statistic, the minimal observable clade size, is introduced. When combined with classical site frequency based statistics, it reduces classification errors considerably.
Aging-Associated Decrease in the Histone Acetyltransferase KAT6B Causes Myeloid-Biased Hematopoietic Stem Cell Differentiation
Authors: Khokhar Eraj Shafiq , Borikar Sneha , Eudy Elizabeth , Stearns Tim , Young Kira , Trowbridge Jennifer J. 
Published: June 2019

SummaryAged hematopoietic stem cells (HSCs) undergo biased lineage priming and differentiation toward production of myeloid cells. A comprehensive understanding of gene regulatory mechanisms causing HSC aging is needed to devise new strategies to sustainably improve immune function in aged individuals. Here, a focused shRNA screen of epigenetic factors reveals that the histone acetyltransferase Kat6b regulates myeloid cell production from hematopoietic progenitor cells. Within the stem and progenitor cell compartment, Kat6b is most highly expressed in long-term (LT)-HSCs and is significantly decreased with aging at the transcript and protein levels. Knockdown of Kat6b in young LT-HSCs causes skewed production of myeloid cells both in vitro and in vivo. Transcriptome analysis identifies enrichment of aging and macrophage-associated gene signatures alongside reduced expression of self-renewal and multilineage priming signatures. Together, our work identifies KAT6B as an epigenetic regulator of LT-HSC aging and a novel target to improve aged immune function.
Post‐mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms
Authors: Fransen Nina L. , Crusius Jakob B. A. , Smolders Joost , Mizee Mark R. , van Eden Corbert G. , Luchetti Sabina , Remmerswaal Ester B. M. , Hamann Jörg , Mason Matthew R. J. , Huitinga Inge 
Published: June 2019

AbstractOver the last few decades, several common single nucleotide polymorphisms (SNPs) have been identified that correlate with clinical outcome in multiple sclerosis (MS), but the pathogenic mechanisms underlying the clinical effects of these SNPs are unknown. This is in part because of the difficulty in the functional translation of genotype into disease‐relevant mechanisms. Building on our recent work showing the association of clinical disease course with post‐mortem MS lesion characteristics, we hypothesized that SNPs that correlate with clinical disease course would also correlate with specific MS lesion characteristics in autopsy tissue. To test this hypothesis, 179 MS brain donors from the Netherlands Brain Bank MS autopsy cohort were genotyped for 102 SNPs, selected based on their reported associations with clinical outcome or their associations with genes that show differential gene expression in MS lesions. Three SNPs linked to MS clinical severity showed a significant association between the genotype and either the proportion of active lesions (rs2234978/FAS and rs11957313/KCNIP1) or the proportion of mixed active/inactive lesions (rs8056098/CLEC16A). Three SNPs linked to MS pathology‐associated genes showed a significant association with either proportion of active lesions (rs3130253/MOG), incidence of cortical gray matter lesions (rs1064395/NCAN) or the proportion of remyelinated lesions (rs5742909/CTLA4). In addition, rs2234978/FAS T‐allele carriers showed increased FAS gene expression levels in perivascular T cells and perilesional oligodendrocytes, cell types that have been implicated in MS lesion formation. Thus, by combining pathological characterization of MS brain autopsy tissue with genetics, we now start to translate genotypes linked to clinical outcomes in MS into mechanisms involved in MS lesion pathogenesis.
Public spending on agricultural productivity and rural commercialization: A comparison of impacts using an economy‐wide approach
Authors: Aragie Emerta , Balié Jean 
Published: June 2019

AbstractMotivationMany developing countries have identified a set of strategic objectives and a longlist of investment areas to promote agricultural production and ensure food security. However, most of these countries lack the financial and technical capacity to execute all of the strategic objectives and investment areas, calling for a robust comparison of their effects.PurposeTaking the case of Ethiopia as an example, this study employs an economy‐wide model and assesses the relative efficiency of alternative investment options on agricultural performance and household welfare. These agricultural investment policies are evaluated under three alternative funding modalities: budget reallocation, donor financing and tax revenue.Approach and methodsTo account for the linkage, and direct and indirect impacts of alternative public expenditure policies, this study adapts an economy‐wide general equilibrium model for Ethiopia calibrated to a well disaggregated social accounting matrix representing the economic structure in 2010.FindingsResults show that the public expenditure options examined could cause significantly different production and welfare responses. Productivity‐enhancing interventions such as input subsidy and irrigation development have superior output and welfare consequences, while policies aimed at smallholder commercialization such as infrastructural development aimed at cutting marketing margins have the least effect, suggesting a need to first prioritize relaxing supply constraints. This ranking of the agricultural policies is robust to the investment financing modalities considered. We, however, observe that financing these projects through income tax could be detrimental to the welfare of urban households.Policy implicationsResults show that in a supply‐constrained economy like that of Ethiopia, governments should focus on agricultural production and productivity‐enhancing interventions (at least in the short run). Reallocation of public funds towards the policies examined should be a principal funding source as this results in superior outcomes. On the other hand, governments should avoid using income tax as a source of finance since this can be highly detrimental to the welfare of urban households.
Hemostatic function in hyperfibrinolytic disseminated intravascular coagulation
Authors: Ishihara Takashi , Nogami Keiji , Onishi Tomoko , Ogiwara Kenichi , Ochi Satoshi , Yamazaki Masaharu , Shima Midori 
Published: June 2019

AbstractBackgroundGlobal hemostatic mechanism(s) in patients with disseminated intravascular coagulation (DIC) are poorly understood. There are few diagnostic criteria of DIC based on overall or global hemostatic mechanisms.MethodsWe have assessed in detailed the dynamic global hemostatic changes using thrombin and plasmin generation assay (T/P‐GA), clot fibrinolytic waveform analysis (CFWA) and not‐activated rotational thromboelastometry (NATEM), in a young girl with DIC associated with acute myeloid leukemia (AML). The ratios of endogenous thrombin potential (T‐EP) and plasmin lag time (P‐LT) relative to normal plasma was sourced from pooled normal plasma from healthy volunteers on T/P‐GA.ResultsThe inverse P‐LT ratio prior to tranexamic acid (TXA) treatment was greater than the T‐EP ratio (1.1–2.8 and 0.83–1.2, respectively). Significant reduction in inverse P‐LT ratio (0.084–1.3) was observed after TXA treatment. The interval from clotting to the initiation of fibrinolysis (fibrinolysis lag time: FLT) in CFWA was significantly shorter than the control at onset (74.2–91.6 s vs 109 s), indicating enhanced fibrinolysis. Data from an adult with acute promyelocytic leukemia‐associated DIC also supportively showed a high inverse P‐LT ratio (2.1) and shortened FLT (83.7 s). The clotting time in patient whole blood using NATEM‐mode during an episode of severe epistaxis markedly shortened beyond control, but returned to normal after the addition of an anti‐tissue factor (TF) monoclonal antibody.ConclusionThe release of intravascular TF contributed to sustained activation of coagulation and subsequent fibrinolytic activity in this patient with AML‐associated DIC, and T/P‐GA could provide better quantitative data than conventional assays in these circumstances.