Miracle-dz/UniFAR-FTUs huggingface dataset:
Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus

Abstract Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early-life health complications and later disease. GDM recurrence is common, affecting 40 to 73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and prepregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify body weight. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of interpregnancy or prepregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy.
HIV-2 Genetic Evolution in Patients with Advanced Disease Is Faster than That in Matched HIV-1 Patients

ABSTRACT The objective of this study was to estimate and compare the evolutionary rates of HIV-2 and HIV-1. Two HIV-2 data sets from patients with advanced disease were compared to matched HIV-1 data sets. The estimated mean evolutionary rate of HIV-2 was significantly higher than the estimated rate of HIV-1, both in the gp125 and in the V3 region of the env gene. In addition, the rate of synonymous substitutions in gp125 was significantly higher for HIV-2 than for HIV-1, possibly indicating a shorter generation time or higher mutation rate of HIV-2. Thus, the lower virulence of HIV-2 does not appear to translate into a lower rate of evolution.
Oral Fluid Nicotine Markers to Assess Smoking Status and Recency of Use

Introduction: Oral fluid collection is noninvasive and easily observed making it an attractive matrix for objectively determining smoking status. Despite large intersubject variability, cotinine oral fluid concentrations correlate with cigarettes smoked per day (CPD). Few studies, however, assessed nicotine markers in oral fluid other than cotinine; other markers might improve smoking status assessment and/or time of last cigarette. Materials and Methods: Smoking histories and oral fluid specimens were collected from nontreatment-seeking light (1-10 CPD) and heavy smokers (greater than 10 CPD) and from environmentally exposed and nonexposed nonsmokers who provided written informed consent for this Institutional Review Board-approved study. Nicotine, cotinine, hydroxycotinine (OH-cotinine), and norcotinine oral fluid concentrations were quantified by liquid chromatography tandem mass spectrometry. Results: Comparison of 1, 3, and 10 ng/mL oral fluid liquid chromatography tandem mass spectrometry cutoffs demonstrated that 10-ng/mL cutoffs performed optimally for cotinine, OH-cotinine, nicotine, and norcotinine identifying 98%, 97%, 88%, and 15% of self-reported smokers; 1% nonsmokers had greater than 10 ng/mL cotinine. No self-reported nonsmoker had greater than 10 ng/mL OH-cotinine, nicotine, or norcotinine. Norcotinine was only identified in smokers' oral fluid. Oral fluid nicotine, cotinine, and nicotine/cotinine ratios were correlated with time of last smoking (r = -0.53, -0.23, and -0.51; P < 0.05) and CPD (r = 0.35, 0.26, and 0.33; P < 0.01), respectively. Discussion and Conclusion: OH-cotinine performed slightly better than cotinine for distinguishing smokers from nonsmokers and should be considered as an additional oral fluid smoking indicator. Further research is required to determine if oral fluid norcotinine is a marker for distinguishing light and heavy smokers. Moderate correlations suggest nicotine, cotinine, and nicotine/cotinine ratios may be useful for determining smoking recency in “spot samples” collected during nicotine cessation treatment.
Anisotropic Cell Expansion Is Affected through the Bidirectional Mobility of Cellulose Synthase Complexes and Phosphorylation at Two Critical Residues on CESA31[OPEN]

Phosphorylation of a subunit of cellulose synthase differentially alters the rate at which cellulose synthase moves in both directions along microtubules, thereby impacting growth and development. Here we report that phosphorylation status of S211 and T212 of the CESA3 component of Arabidopsis (Arabidopsis thaliana) cellulose synthase impacts the regulation of anisotropic cell expansion as well as cellulose synthesis and deposition and microtubule-dependent bidirectional mobility of CESA complexes. Mutation of S211 to Ala caused a significant decrease in the length of etiolated hypocotyls and primary roots, while root hairs were not significantly affected. By contrast, the S211E mutation stunted the growth of root hairs, but primary roots were not significantly affected. Similarly, T212E caused a decrease in the length of root hairs but not root length. However, T212E stunted the growth of etiolated hypocotyls. Live-cell imaging of fluorescently labeled CESA showed that the rate of movement of CESA particles was directionally asymmetric in etiolated hypocotyls of S211A and T212E mutants, while similar bidirectional velocities were observed with the wild-type control and S211E and T212A mutant lines. Analysis of cell wall composition and the innermost layer of cell wall suggests a role for phosphorylation of CESA3 S211 and T212 in cellulose aggregation into fibrillar bundles. These results suggest that microtubule-guided bidirectional mobility of CESA complexes is fine-tuned by phosphorylation of CESA3 S211 and T212, which may, in turn, modulate cellulose synthesis and organization, resulting in or contributing to the observed defects of anisotropic cell expansion.
Chronic Mesenteric Ischemia: Patient Outcomes Using Open Surgical Revascularization

Background: Chronic mesenteric ischemia (CMI) is a rare disease. Open treatment (OT) remains a valuable treatment option. We analyzed patient outcomes after OT and investigated health-related quality of life (HRQoL). Methods: Data were analyzed retrospectively. The investigation period was from January 1, 2001, to December 31, 2014. We investigated mortality and patency rates using Kaplan-Meier analysis. HRQoL was measured using a 36-item health survey. Various statistical methods were employed. Results: A total of 100 patients (celiac trunk [TC: n = 23], superior mesenteric artery [SMA: n = 26], or both [n = 51]) were included. Median follow-up was 5 ± 35 months. One-year survival rate for TC was 75 ± 11%, for SMA: 79 ± 10%, and for both: 96 ± 3%. TC 5-year survival was 75 ± 11% (SMA: 57 ± 16%: both: 80 ± 8%). Obesity and the length of hospital stay were independently associated with patient survival (p < 0.05). Primary 1-year patency rate was 60 ± 13% for TC (SMA: 86 ± 10%; both: 71 ± 8%) and secondary 1-year patency rate was 84 ± 9% for TC (SMA: 100%; both: 79 ± 7%). HRQoL was inferior compared to the German normative data (p < 0.05). Conclusion: CMI overlaps between gastrointestinal and vascular surgery. OT is safe, and simultaneous revascularization of the TC and the SMA does not affect mortality. Patients would not necessarily benefit from OT in terms of HRQoL.
Increased deficits in emotion recognition and regulation in children and adolescents with exogenous obesity

Abstract Objectives: In this study we aimed to evaluate emotion recognition and emotion regulation skills of children with exogenous obesity between the ages of 11 and 18 years and compare them with healthy controls. Methods: The Schedule for Affective Disorders and Schizophrenia for School Aged Children was used for psychiatric evaluations. Emotion recognition skills were evaluated using Faces Test and Reading the Mind in the Eyes Test. The Difficulties in Emotions Regulation Scale was used for evaluating skills of emotion regulation. Results: Children with obesity had lower scores on Faces Test and Reading the Mind in the Eyes Test, and experienced greater difficulty in emotional regulation skills. Conclusions: Improved understanding of emotional recognition and emotion regulation in young people with obesity may improve their social adaptation and help in the treatment of their disorder. To the best of our knowledge, this is the first study to evaluate both emotional recognition and emotion regulation functions in obese children and obese adolescents between 11 and 18 years of age.
Complement activation in pregnancy: too much of a good thing?

See related article, pp 1332-1337 Preeclampsia and other hypertensive disorders of pregnancy continue to be major contributors to maternal mortality and morbidity worldwide.1 Currently, primary treatment for preeclampsia centers on the management of symptoms until delivery is indicated; hence, early onset preeclampsia is strongly associated with fetal growth restriction and is one of the leading causes of preterm birth.1 A wide variety of putative factors and pathways have been implicated in the development of this pregnancy-specific syndrome.1 Indeed, characterization of biomarkers for the identification of patients at risk for developing preeclampsia continues to be an important endeavor. The complement system is a humoral immune amplification system, and products of complement system activation have been implicated both as biomarkers for the disease and as factors important for the development of preeclampsia. The study by Buurma et al2 in this issue of Hypertension takes a critical step toward identifying the important pathway of complement activation leading to excessive local complement activation in the preeclamptic placenta, as well as demonstrating key complement regulatory proteins that are increased in preeclampsia presumably to limit activation of the pathophysiologic pathway. The original discovery of the complement system focused on its ability to complement the actions of antibody in host defense and bacterial killing. As part of innate immunity, the complement system contributes to survival, and components are found in species as ancient as horseshoe crabs. Although basal complement activity is controlled by numerous regulators, excessive activation contributes to autoimmune diseases, including arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Interestingly, individuals with systemic lupus erythematosus and antiphospholipid syndrome are also at increased risk for adverse fetal outcomes and hypertension during pregnancy. A brief overview of the most relevant aspects of the complement system is illustrated in the Figure. Central to all 3 …
Alterations of white matter tracts following neurotoxic hippocampal lesions in macaque monkeys: A diffusion tensor imaging study

Diffusion tensor imaging (DTI) is a valuable tool for assessing presumptive white matter alterations in human disease and animal models. The current study used DTI to examine the effects of selective neurotoxic lesions of the hippocampus on major white matter tracts and anatomically related brain regions in macaque monkeys. Two years postlesion, structural MRI, and DTI sequences were acquired for each subject. Volumetric assessment revealed a substantial reduction in the size of the hippocampus in experimental subjects, averaging 72% relative to controls, without apparent damage to adjacent regions. DTI images were processed to yield measures of fractional anisotropy (FA), apparent diffusion coefficient (ADC), parallel diffusivity (lADC), and perpendicular diffusivity (tADC), as well as directional color maps. To evaluate potential changes in major projection systems, a region of interest (ROI) analysis was conducted including the corpus callosum, fornix, temporal stem, cingulum bundle, ventromedial prefrontal white matter, and optic radiations. Lesion‐related abnormalities in the integrity of the fiber tracts examined were limited to known hippocampal circuitry, including the fornix and ventromedial prefrontal white matter. These findings are consistent with the notion that hippocampal damage results in altered interactions with multiple memory‐related brain regions, including portions of the prefrontal cortex. © 2010 Wiley‐Liss, Inc.
Metacognition: An Effective Tool to Promote Success in College Science Learning

Metacognition has been shown to lead to deeper, more durable, and more transferable learning (Bransford, Brown, & Cocking, 2000). This article describes a case study in which metacognition was introduced to undergraduate science (chemistry) classrooms. Students came to understand the difference between superficial memorization and real learning through specific classroom interventions, which were also designed to help students develop metacognitive learning strategies. The aim of the study was to instruct educators how to incorporate metacognition in college science classrooms, and the improved cognitive and affective learning of students indicated its significance. On the basis of students' reflections, we assert that implementation of these strategies will contribute to increased learning not just in chemistry but also across other courses and curricula. T he constructivist theory of learning (Bodner, 1986, 2001) posits that students construct knowledge from their own experiences. Knowledge construction includes cognitive learning, acquisition of content knowledge, and the ability to apply that knowledge to new situations (Bretz, 2001). In order to engage in constructivist learning, students must possess the necessary learning strategies, but not all do. In addition to the cognitive domain, real learning also includes the affective and metacognitive domains (Vermunt & Verloop, 1999). The affective learning domain comprises a student's attitude about learning, willingness to actively engage in learning activities , and skill in evaluating his own ability and performance in a subject area. In 1976, Flavell defined meta-cognition as " knowledge concerning one's own cognitive processes and products or anything related to them " (Flavell, 1976, p. 232). Often metacognition is described as " thinking about one's own think-students aware of the gap between superficial and real learning and how to help them develop effective learning strategies through metacognition. We begin by presenting the surveys used to gauge students' effective use of learning strategies prior to and after the classroom intervention. We then describe the intervention and discuss its impact on student performance and how it changed students' perceptions of themselves as skilled learners. We conclude by presenting the limitations of the study and implications for future research. Instruments Table 1 shows the Effective Learning Strategies Survey. The questions in the survey appear in a specific order designed to prepare students for the intervention to follow. The first two questions help students differentiate among the various levels of intellectual behavior according to the revised Bloom's taxonomy (Anderson & Krathwohl, 2001), in which each level builds on …
Increased glutaredoxin-1 and decreased protein S-glutathionylation in sputum of asthmatics

To the Editor: Total reduced glutathione (GSH), the main pulmonary antioxidant, is increased in asthma patients and, in some studies, increased amounts of oxidised glutathione (GSSG) were also found. In addition, enzymes that regulate the GSH redox cycle are altered in asthmatics (reviewed in [1]). GSH, with its redox cycle partners, serves to maintain the reduced state of protein thiols, which can be achieved by scavenging oxidants or by the covalent reversible binding of GSH to protein thiols. The latter occurs under physiological conditions, is induced upon mild oxidative stress and is known as S -glutathionylation (PSSG) [2]. PSSG protects targeted thiols from irreversible oxidations and can modulate protein function. Of significant relevance in asthma, SERCA (sarco/endoplasmic reticulum calcium ATPase) is activated by PSSG, increasing smooth muscle relaxation, and PSSG of the RyR (ryanodine receptor) calcium channel was associated with impaired coupling. With respect to inflammation, nuclear factor-κB and activator protein-1 are negatively affected by PSSG (reviewed in [2]). GSH can be removed from proteins by glutaredoxins (Grx), which restores the function of proteins targeted by PSSG [2]. The Grx1 isoform localises to the cytosol, and Grx2 to mitochondria and the nucleus. Grx1 can also reduce low molecular weight disulfides and, thus, proteins with functionally important disulfide bonds could also be affected by Grx1 alterations. In contrast to damaging oxidations and measurements of GSH, PSSG and Grx have rarely been studied in lung diseases, and never in conjunction. In chronic obstructive pulmonary disease (COPD), Grx1-positive alveolar macrophages were negatively correlated with forced expiratory volume in 1 s (FEV1) and sputum Grx1 levels were higher during exacerbations [3]. In a murine model of allergic airway disease, we found increased Grx1 expression and activity [4]. Given the importance of …
Plasma IL-37 Elevated in Patients with Chronic Heart Failure and Predicted Major Adverse Cardiac Events: A 1-Year Follow-Up Study

A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in the development and progression of chronic heart failure (CHF). However, there is limited information about the role of novel cytokine interleukin-37 (IL-37) in heart failure. We measured plasma IL-37 levels by enzyme-linked immunosorbent assay (ELISA) in 158 patients with chronic heart failure and 30 control subjects. Our results showed that plasma IL-37 levels were significantly elevated in patients with CHF compared with healthy controls (143.73 ± 26.83 pg/ml versus 45.2 ± 11.56 pg/ml, P < 0.001). Furthermore, plasma IL-37 levels were positively correlated with hs-CRP, hs-TnT, and NT-proBNP and negatively correlated with left ventricular ejection function (LVEF). 11 patients died of cardiovascular cause, and 27 HF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that plasma IL-37 is an independent predictor of major adverse cardiac events (MACE). Furthermore, CHF patients with >99 pg/ml plasma IL-37 had significantly higher incidences of MACE within 12 months. Our data suggest that plasma IL-37 may play a role in the pathogenesis of CHF and may be a novel predictor of poor prognosis in HF patients.
Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: results of a phase I-II randomized clinical trial.

BACKGROUND Dose-sparing strategies are being explored for vaccines against pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide (AlOH) adjuvant. METHODS A total of 600 healthy subjects (age, 18-49 years) were randomized to receive 2 vaccinations 1 month apart with subvirion inactivated influenza A/H5N1 vaccine containing 7.5, 15, or 45 microg of hemagglutinin (HA), with or without 600 microg of aluminum hydroxide (AlOH), or 3.75 microg of HA, with or without 300 microg of AlOH. Serum specimens were obtained for antibody assays before and 1 month after each vaccination. RESULTS All formulations were safe. Injection site discomfort was more frequent in groups given vaccines with AlOH. Dose-related increases in antibody responses were noted after both vaccinations (P< .001) geometric mean titers of hemagglutination inhibition antibody in vaccines with and without AlOH, respectively, were 5.4 and 5.4 for subjects who received 3.75 microg of HA, 7.7 and 5.3 for those who received 7.5 microg of HA, 8.1 and 8.5 for those who received 15 microg of HA, and 14.8 and 12 for those who received 45 microg of HA. A > or =4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 microg of HA with or without AlOH, respectively; in 14% and 0% who received 7 microg of HA; in 14% and 13% who received 15 microg of HA; and in 33% and 25% who received 45 microg of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 microg of HA, but responses in subjects who received 7.5 microg of HA without AlOH were unexpectedly low. CONCLUSION Overall, a meaningful beneficial effect of AlOH adjuvant was not observed. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00296634 .
The cDNA-derived Investigational Human Parainfluenza Virus Type 3 Vaccine rcp45 Is Well Tolerated, Infectious, and Immunogenic in Infants and Young Children

Background: Human parainfluenza virus type 3 (HPIV3) is an important yet underappreciated cause of lower respiratory tract illness in children, and a licensed vaccine is not yet available. Methods: A live-attenuated investigational HPIV3 vaccine virus designated rcp45 was derived from cDNA by using reverse genetics. rcp45 is genetically similar to the biologically derived cp45 vaccine virus and contains all of the known attenuating mutations of cp45, but has the advantage of a short, well-characterized passage history. We evaluated the tolerability, infectivity, and immunogenicity of 2 intranasal doses of rcp45 administered 4 to 10 weeks apart in a placebo-controlled, double-blind trial. A total of 45 infants and children between 6 and 36 months of age participated in this study. Tolerability and antibody responses to vaccine or placebo were assessed in all recipients. Infectivity was assessed by quantitation of vaccine virus shedding in a subset of vaccinated children. Results: rcp45 was well tolerated and highly infectious in HPIV3-seronegative children. A second dose of vaccine administered 4 to 10 weeks after the first dose was restricted in replication and did not boost serum antibody responses. The stability of 9 cp45 mutations, including the 6 major attenuating mutations, was examined and confirmed for viral isolates from 10 children. Conclusions: The level of attenuation and immunogenicity of cDNA-derived rcp45 is comparable to what was previously observed with the biologically derived cp45 vaccine, and preliminary data suggest that the attenuating mutations in this vaccine virus are genetically stable. Continued clinical development of rcp45 is warranted.
Ca2+-store-dependent and -independent reversal of Stim1 localization and function

Stim1 responds to depletion of ER Ca2+ stores by rearranging from tubular structures throughout the ER into punctate structures near the plasma membrane, where it activates Orai store-operated Ca2+ entry (SOCE) channels. However, the mechanism and structural determinants of the localization and reversal of Stim1 puncta formation are poorly understood. Using HEK293 cells expressing Stim1 tagged with enhanced yellow fluorescent protein (EYFP-Stim1), we show that the basis for SOCE termination is the reversal of the punctate Stim1 localization, which absolutely depends on SOCE-dependent store refilling. We also describe rapid, store-independent reversal of EYFP-Stim1 punctae by the ML-9 inhibitor of myosin-light-chain kinase (MLCK). ML-9 similarly inhibited SOCE and the Ca2+-release-activated Ca2+ (CRAC) current. Reversal by ML-9 resulted in full re-establishment of the tubular EYFP-Stim1 localization. A constitutively active EF-hand mutant of EYFP-Stim1 was also reversed by ML-9, regardless of the Ca2+ store content. Inhibition by ML-9 was not due to MLCK inhibition as other inhibitors of MLCK had no effect. Finally, we provide evidence that EYFP-Stim1 punctae form in specific predetermined cellular loci. We conclude that SOCE is tightly coupled to formation of Stim1 puncta, and both SOCE and puncta formation involve a dynamic, reversible signaling complex that probably consists of components in addition to Stim1 and Orai channels.