bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediators in Preterm Infants With Late‐onset Sepsis
Authors: Abdel‐Hady Hesham , Yahia Sohier , Megahed Ahmed , Mosbah Abeer , Seif Basma , Nageh Eman , Bhattacharjee Indrani , Aly Hany 
Published: January 2019

ABSTRACTObjective:To evaluate biochemical and clinical effects of 2 different doses of vitamin D supplementation in preterm infants with late‐onset sepsis (LOS).Study Design:A double blinded randomized controlled stratified trial included preterm infants with gestational age (GA) ≥28 weeks with LOS. Subjects were randomly assigned to receive 400 or 800 IU/day of vitamin D3. Serum concentrations of 25(OH)D, TNF‐α, and IL‐6 were measured at enrollment, 7 days after vitamin D supplementation, and at 40 weeks of postmenstrual age (PMA). Short‐term outcomes and growth parameters were assessed.Results:A total of 50 infants were enrolled, 25 in each group. Seventy‐six percentage of enrolled infants were vitamin D‐deficient at enrollment in both groups whereas only one infant in the 400 IU and none in the 800 IU group remained deficient at 40 week's PMA; vitamin D concentrations at 40 weeks PMA were 54.8 ± 35.1 and 67.4 ± 37.1 ng/mL, respectively, P = 0.01). None of the infants enrolled in the study had signs of vitamin D toxicity. Serum pro‐inflammatory cytokines IL‐6 and TNF‐ α concentrations decreased at 1 week and at discharge in both groups without differences between groups. The 2 groups did not differ in anthropometric measurements, duration of oxygen and respiratory support, duration of antimicrobial use, length of hospital stay, and mortality.Conclusions:A dose of 400 IU of vitamin D was adequate to treat vitamin D deficiency in the majority of premature infants with LOS. The 2 dosing regimens did not differ in clinical or biochemical changes.
Transient Exocrine Pancreatic Insufficiency in Children
Authors: Garah Jamal , Rosen Irit , Shaoul Ron 
Published: January 2019

ABSTRACTObjectives:Pancreatic insufficiency in children is usually associated with diseases such as cystic fibrosis, Shwachman‐Diamond syndrome, or chronic pancreatitis. Fecal elastase‐1 is a reliable laboratory test for the diagnosis of exocrine pancreatic insufficiency (EPI). Transient pancreatic insufficiency has been rarely described and data on this entity are lacking in the medical literature. In this retrospective study we report 17 cases of transient pancreatic insufficiency presented mainly with failure to thrive and/or diarrhea.Methods:We followed 43 children (age range 1 month–18 years) with low fecal elastase‐1 in our institution between the years 2009 and 2017. We followed growth and laboratory results (particularly, complete blood count, albumin, transaminases, celiac serology, sweat test, and fat‐soluble vitamins). Elastase levels <200 mg/g were considered as pancreatic insufficiency.Results:Twenty‐six were excluded due to missing data, a comorbidity or being syndromatic. Enrolled children (17) were all otherwise healthy.The median age at diagnosis was 3 years (range 0.2–15 years), 11 girls and 6 boys. Their main presenting symptoms were failure to thrive and/or diarrhea. Median fecal elastase‐1 levels were 71 mg/g (range 18–160). Median time for normalization was 6 months (range 1–48 months). Abdominal sonography, celiac serology, and sweat test were normal for all patients. Most patients were treated with pancreatic enzymes until resolution.Conclusions:Transient EPI without clear etiology should be in the differential diagnosis of EPI after ruling out known etiologies. The resolving course pattern may be attributed to an unidentified infectious agent. Further studies to assess the etiology are mandated.
Does Changing Antiretroviral Therapy in the First Trimester of Pregnancy for Safety Concerns Have an Impact on Viral Suppression?
Authors: Peyronnet Violaine , Warszawski Josiane , Sibiude Jeanne , Dialla Olivia , Bourgeois-Moine Agnès , Bui Eida , Toulza Caroline Simon , Peretti Delphine , Brunet-Cartier Cécile , Avettand-Fenoel Véronique , Chenadec Jérôme L. , Faye Albert , Tubiana Roland , Mandelbrot Laurent ,   for the ANRS EPF-French Perinatal Cohort Study
Published: January 2019

Objective:
To determine whether changing antiretroviral therapy (ART) during pregnancy because of concern about fetal risks led to poorer virological outcomes.

Methods:
All pregnancies in women with HIV-1 infection enrolled in the national multicenter prospective French Perinatal cohort at 14 week gestation or more were included between January 2005 and December 2015, if the mother was on ART at conception with a plasma viral load <50 copies/mL. The reasons for a change in the ART were analyzed according to treatment guidelines at the time of the pregnancy and defined as for safety concerns in the absence of reported maternal intolerance. Virological and pregnancy outcomes were studied by survival analysis and logistic regression adjusted for a propensity score established for each patient according to baseline characteristics.

Results:
Of 7079 pregnancies in the overall cohort, 1797 had ART at conception with a viral load <50 copies/mL before 14 week gestation. Of these, 22 changed regimens in the first trimester for intolerance, and 411 of the remaining 1775 (23%) solely for safety concerns. The proportion of change was higher when the initial treatment was not recommended in the national guidelines (OR adjusted: 23.1 [14.0–38.2]), than when it was an alternative option (ORa: 2.2 [1.3–3.7]), as compared to recommended first-line regimens. Treatment changes for safety concerns did not lead to poorer virological control, compared with pregnancies without such changes (19.3% vs. 15.6%, HRa: 1.0 [0.7–1.4]).

Conclusions:
Changing ART early in pregnancy to regimens considered safer for pregnancy, and neonatal health did not have a destabilizing effect on viral suppression.
Identification of Physiological Response Functions to Correct for Fluctuations in Resting-State fMRI related to Heart Rate and Respiration
Authors: Kassinopoulos Michalis , Mitsis Georgios D. 
Published: January 2019

AbstractFunctional magnetic resonance imaging (fMRI) is widely viewed as the gold standard for studying brain function due to its high spatial resolution and non-invasive nature. However, it is well established that changes in breathing patterns and heart rate strongly influence the blood oxygen-level dependent (BOLD) fMRI signal and this, in turn, can have considerable effects on fMRI studies, particularly resting-state studies. The dynamic effects of physiological processes are often quantified by using convolution models along with simultaneously recorded physiological data. In this context, physiological response function (PRF) curves (cardiac and respiratory response functions), which are convolved with the corresponding physiological fluctuations, are commonly employed. While it has often been suggested that the PRF curves may be region- or subject- specific, it is still an open question whether this is the case. In the present study, we propose a novel framework for the robust estimation of PRF curves and use this framework to rigorously examine the implications of using population-, subject-, session- and scan-specific PRF curves. The proposed framework was tested on resting-state fMRI and physiological data from the Human Connectome Project. Our results suggest that PRF curves vary significantly across subjects and, to a lesser extent, across sessions from the same subject. These differences can be partly attributed to physiological variables such as the mean and variance of the heart rate during the scan. The proposed methodological framework can be used to obtain robust scan-specific PRF curves from data records with duration longer than 5 minutes, exhibiting significantly improved performance compared to previously defined canonical cardiac and respiration response functions. Besides removing physiological confounds from the BOLD signal, accurate modeling of subject- (or session-/scan-) specific PRF curves is of importance in studies that involve populations with altered vascular responses, such as aging subjects.HighlightsPhysiological response functions (PRF) vary considerably across subjects/sessionsScan-specific PRF curves can be obtained from data records longer than 5 minutesThe shape of the cardiac response function is linked to the mean heart rate (HR)Brain regions affected by HR and breathing patterns exhibit substantial overlapHR and breathing patterns affect distinct regions as compared to cardiac pulsatility
Integrating Quality of Life and Survival Outcomes Cardiovascular Clinical Trials: Results from the PARTNER Trial
Authors: Spertus Jacob V. , Hatfield Laura A. , Cohen David J. , Arnold Suzanne V. , Ho Martin , Jones Philip G. , Leon Martin , Zuckerman Bram , Spertus John A. 
Published: January 2019

ABSTRACTBackgroundSurvival and health status (e.g., symptoms and quality of life) are key outcomes in clinical trials of heart failure treatment. However, health status can only be recorded on survivors, potentially biasing treatment effect estimates when there is differential survival across treatment groups. Joint modeling of survival and health status can address this bias.Methods and ResultsWe analyzed patient-level data from the PARTNER 1B trial of transcatheter aortic valve replacement (TAVR) versus standard care. Health status was quantified with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at randomization, 1, 6, and 12 months. We compared hazard ratios for survival and mean differences in KCCQ scores at 12 months using several models: the original growth curve model for KCCQ scores (ignoring death), separate Bayesian models for survival and KCCQ scores, and a Bayesian joint longitudinal-survival model fit to either 12 or 30 months of survival follow-up. The benefit of TAVR on 12-month KCCQ scores was greatest in the joint model fit to all survival data (mean difference = 33.7 points; 95% CrI: 24.2, 42.4), followed by the joint model fit to 12 months of survival follow-up (32.3 points; 95% CrI: 22.5, 41.5), a Bayesian model without integrating death (30.4 points; 95% CrI: 21.4, 39.3), and the original growth curve model (26.0 points; 95% CI: 18.7, 33.3). At 12 months, the survival benefit of TAVR was also greater in the joint model (hazard ratio = 0.50; 95% CrI: 0.32, 0.73) than in the non-joint Bayesian model (0.54; 95% CrI: 0.37, 0.75) or the original Kaplan-Meier estimate (0.55; 95% CI: 0.40, 0.74).ConclusionsIn patients with severe symptomatic aortic stenosis and prohibitive surgical risk, the estimated benefits of TAVR on survival and health status compared with standard care were greater in joint Bayesian models than other approaches.
Comparing alternative cholera vaccination strategies in Maela refugee camp using a transmission model
Authors: Havumaki Joshua , Meza Rafael , Phares Christina R , Date Kashmira , Eisenberg Marisa C 
Published: January 2019

AbstractBackgroundCholera remains a major public health concern, particularly in refugee camps, which may contend with overcrowding and scarcity of resources. Maela, the largest long-standing refugee camp in Thailand, experienced four cholera outbreaks between 2005 and 2010. In 2013, a cholera vaccine campaign was implemented in the camp. To assist in the evaluation of the campaign and planning for subsequent campaigns, we developed a mathematical model of cholera in Maela.MethodsWe formulated a Susceptible-Infectious-Water-Recovered-based cholera transmission model and estimated parameters using incidence data from 2010. We next evaluated the reduction in cases conferred by several immunization strategies, varying timing, effectiveness, and resources (i.e., vaccine availability). Finally, we generated post-campaign case forecasts, to determine whether a booster campaign was needed.ResultsWe found that preexposure vaccination can substantially reduce the risk of cholera even when the < 50% of the population is given the full two-dose series. Additionally, the preferred number of doses per person should be considered in the context of one vs. two dose effectiveness and vaccine availability. For reactive vaccination, a trade-off between timing and effectiveness was revealed, indicating that it may be beneficial to give one dose to more people rather than two doses to fewer people, given that a two-dose schedule would incur a delay in administration of the second dose. Forecasting using realistic coverage levels predicted that there was no need for a booster campaign in 2014 (consistent with our predictions, there was not a cholera epidemic in the 2014 season).ConclusionsOur analyses suggest that vaccination in conjunction with ongoing water sanitation and hygiene efforts provides an effective strategy for cholera outbreaks in refugee camps. Effective preexposure vaccination depends on timing and effectiveness. If a camp is facing an outbreak, delayed distribution of vaccines can substantially alter the effectiveness of reactive vaccination, suggesting that quick distribution of vaccines may be more important than ensuring every individual receives both vaccine doses.
Heparan sulfate expression on B cells modulates IgM expression in aged mice and steady-state plasma cell numbers
Authors: Trujillo Damian L. , Jarousse Nadine , Coscoy Laurent 
Published: January 2019

AbstractHeparan sulfate (HS) modulates many cellular processes including adhesion, motility, ligand-receptor interaction, and proliferation. We have previously reported that murine B cells strongly upregulate cell surface HS upon exposure to type I interferon, TLR-ligands, or B cell receptor stimulation. To investigate the role of HS on B cellsin vivo, we utilized EXT1lox/loxCD19-Cre conditional KO mice, which are incapable of synthesizing HS in B cells. We found that suppressing HS expression on B cells has no overt effect in B cell development, localization, or motility. However, we did observe that EXT1 conditional KO mice have decreased poly-reactive IgM in naïve aged mice relative to littermate control mice. Despite this decrease in poly-reactive IgM, EXT1 conditional KO mice mounted a normal B cell response to both model antigens and influenza infection. We also observed decreased plasma cells in EXT1 conditional KO mice after influenza infection. Although EXT1 conditional KO mice have decreased plasma cells, these mice still had comparable numbers of influenza-specific antibody secreting cells to littermate control mice. The findings presented here suggest that HS expression on B cells does not play a major role in B cell development or overall B cell function but instead might be involved in fine-tuning B-cell responses.
Plasmodium capraeinfection is negatively correlated with infection ofTheileria ovisandAnaplasma ovisin goats
Authors: Hakimi Hassan , Sarani Ali , Takeda Mika , Kaneko Osamu , Asada Masahito 
Published: January 2019

AbstractTheileria, Babesia, andAnaplasmaare tick-borne pathogens affecting livestock industries worldwide. In this study, we surveyed the presence ofBabesia ovis, Theileria ovis, Theileria lestoquardi, Anaplasma ovis, Anaplasma phagocytophilum, andAnaplasma marginalein 200 goats from 3 different districts in Sistan and Baluchestan province, Iran. Species-specific diagnostic PCR and sequence analysis revealed that 1.5%, 12.5%, and 80% of samples were positive forT. lestoquardi, T. ovis, andA. ovis, respectively. Co-infections of goats with up to 3 pathogens were seen in 22% of the samples. We observed a positive correlation betweenA. ovisandT. ovisinfection. In addition, by analyzing the data with respect toPlasmodium capraeinfection in these goats, a negative correlation was found betweenP. capraeandA. ovisand betweenP. capraeandT. ovis. This study contributes to understanding the epidemiology of vector-borne pathogens and their interplay in goats.ImportanceTick-borne pathogens include economically important pathogens restricting livestock farming worldwide. In endemic areas livestock are exposed to different tick species carrying various pathogens which could result in co-infection with several tick-borne pathogens in a single host. The co-infection and interaction among pathogens are important in determining the outcome of disease. Little is known about pathogen interactions in the vector and the host. In this study, we show for the first time that co-infection ofP. caprae, a mosquito transmitted pathogen, withT. ovisandA. ovis. Analysis of goat blood samples revealed a positive correlation betweenA. ovisandT. ovis. Moreover, a negative correlation was seen betweenP. caprae, a mosquito transmitted pathogen, and the tick-borne pathogensT. ovisorA. ovis.
Does testosterone impair men’s cognitive empathy? Evidence from two large-scale randomized controlled trials
Authors: Nadler Amos , Camerer Colin F. , Zava David T. , Ortiz Triana L. , Watson Neil V. , Carré Justin M. , Nave Gideon 
Published: January 2019

AbstractThe capacity to infer others’ mental states (known as “mind reading” and “cognitive empathy”) is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia. Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small-sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (N=243 and N=400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.
Expression of glucocorticoid and mineralocorticoid receptor genes co-vary with a stress-related colour signal in barn owls
Authors: Béziers Paul , Ducrest Anne-Lyse , San-Jose Luis M. , Simon Céline , Roulin Alexandre 
Published: January 2019

AbstractGlucocorticoid hormones are important intermediates between an organism and its environment. They enable an organism to adjust its behavioural and physiological processes in response to environmental changes by binding to mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) expressed in many tissues, including the integument. The regulation of glucocorticoids covaries with melanin-based colouration in numerous species, an association that might result from the melanocortin system and evolve within a signalling context. Most studies have focused on the circulating levels of glucocorticoids disregarding the receptors that mediate their action and could partly account for the covariation between the regulation of stress and melanin-based coloration. We investigated the association between melanin-based coloration and the gene expression levels of GR and MR but also of the melanocortin system and melanogenesis in the growing feathers of nestling barn owls (Tyto alba). We also considered the expression of genes related to the melanocortin system and melanogenesis to better understand the origin of the link between the expression of receptors to which corticosterone binds and melanin-based coloration. Nestling barn owls displaying larger black feather spots expressed GR and MR at lower levels than did smaller-spotted individuals. Because the expression of the GR and MR genes was positively, rather than negatively, correlated with the expression of melanogenic genes, we suggest that the link between melanin-based coloration, GR and MR is not directly associated to melanogenesis. The finding that the expression of GR and MR was positively associated with the expression of the PCSK2 gene (encoding the protein convertase responsible for post-translational modification of the proopiomelanocortin hormone) suggests that the melanocortin system may be implicated in the establishment of the covariation between melanism and the expression of receptors to which glucocorticoids bind. Together with previous studies, our results suggest that coloration is not only related to the production of glucocorticoids but also to the sensitivity of the integument to glucocorticoids.
Novel signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
Authors: Mutlak Yara Eid , Aweida Dina , Volodin Alexandra , Ayalon Bar , Dahan Nitsan , Parnis Anna , Cohen Shenhav 
Published: January 2019

ABSTRACTSignaling through the insulin receptor governs central physiological functions related to cell growth and metabolism. Here we show by tandem native protein complex purification approach and super-resolution STED microscopy that insulin receptor activity requires association with the fundamental structural module in muscle, the dystrophin glycoprotein complex (DGC), and the desmosomal component plakoglobin (γ-catenin). The integrity of this high-molecular-mass assembly renders skeletal muscle susceptibility to insulin because DGC-insulin receptor dissociation by plakoglobin downregulation reduced insulin signaling and caused atrophy. Furthermore, impaired insulin receptor function in muscles from diabetic mice reduced plakoglobin-DGC-insulin receptor content on the plasma membrane; however, plakoglobin overexpression alone restored DGC association with the insulin receptor, and stimulated glucose uptake. Our findings establish DGC as a signaling hub, containing plakoglobin as an auxiliary subunit, and provide a possible mechanism for the insulin resistance in Duchenne Muscular Dystrophy, and for the cardiomyopathies seen with plakoglobin mutations.
Molecular framework for TIR1/AFB-Aux/IAA-dependent auxin sensing controlling adventitious rooting in Arabidopsis
Authors: Lakehal Abdellah , Chaabouni Salma , Cavel Emilie , Le Hir Rozenn , Ranjan Alok , Raneshan Zahra , Novák Ondřej , Păcurar Daniel I. , Perrone Irene , Jobert François , Gutierrez Laurent , Bakò Laszlo , Bellini Catherine 
Published: January 2019

ABSTRACTIn Arabidopsis thaliana, canonical auxin-dependent gene regulation is mediated by 23 transcription factors from the AUXIN RESPONSE FACTOR (ARF) family interacting with 29 auxin/indole acetic acid repressors (Aux/IAA), themselves forming coreceptor complexes with one of six TRANSPORT INHIBITOR1/AUXIN-SIGNALLING F-BOX (TIR1/AFB) PROTEINS. Different combinations of co-receptors drive specific sensing outputs, allowing auxin to control a myriad of processes. Considerable efforts have been made to discern the specificity of auxin action. However, owing to a lack of obvious phenotype in single loss-of-function mutants in Aux/IAA genes, most genetic studies have relied on gain-of-function mutants, which are highly pleiotropic. Using loss-of-function mutants, we show that three Aux/IAA proteins interact with ARF6 and/or ARF8, which we have previously shown to be positive regulators of AR formation upstream of jasmonate, and likely repress their activity. We also demonstrate that TIR1 and AFB2 are positive regulators of adventitious root formation and suggest a dual role for TIR1 in the control of JA biosynthesis and conjugation, as revealed by upregulation of several JA biosynthesis genes in the tir1-1 mutant. We propose that in the presence of auxin, TIR1 and AFB2 form specific sensing complexes with IAA6, IAA9 and/or IAA17 that modulate JA homeostasis to control AR initiation.