Miracle-dz/UniFAR-FTUs huggingface dataset:
Holoendemic Malaria Exposure Is Associated with Altered Epstein-Barr Virus-Specific CD8+ T-Cell Differentiation

ABSTRACT Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a major risk factor for endemic Burkitt lymphoma (eBL), still one of the most prevalent pediatric cancers in equatorial Africa. Although malaria infection has been associated with immunosuppression, the precise mechanisms that contribute to EBV-associated lymphomagenesis remain unclear. In this study, we used polychromatic flow cytometry to characterize CD8+ T-cell subsets specific for EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens in individuals with divergent malaria exposure. No malaria-associated differences in EBV-specific CD8+ T-cell frequencies were observed. However, based on a multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1 expression, we found that individuals living in regions with intense and perennial (holoendemic) malaria transmission harbored more differentiated EBV-specific CD8+ T-cell populations that contained fewer central memory cells than individuals living in regions with little or no (hypoendemic) malaria. This profile shift was most marked for EBV-specific CD8+ T-cell populations that targeted latent antigens. Importantly, malaria exposure did not skew the phenotypic properties of either cytomegalovirus (CMV)-specific CD8+ T cells or the global CD8+ memory T-cell pool. These observations define a malaria-associated aberration localized to the EBV-specific CD8+ T-cell compartment that illuminates the etiology of eBL.
The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1.

Immune activation associated with HIV-1 infection contributes to morbidity and mortality. We studied whether chloroquine, through Toll-like receptor (TLR) antagonist properties, could reduce immune activation thought to be driven by TLR ligands, such as gut-derived bacterial elements and HIV-1 RNAs. AIDS Clinical Trials Group A5258 was a randomized, double-blind, placebo-controlled study in 33 HIV-1-infected participants off antiretroviral therapy (ART) and 37 participants on ART. Study participants in each cohort were randomized 1:1 to receive chloroquine 250 mg orally for the first 12 weeks then cross over to placebo for 12 weeks or placebo first and then chloroquine. Combining the periods of chloroquine use in both arms of the on-ART cohort yielded a modest reduction in the proportions of CD8 T cells co-expressing CD38 and DR (median decrease = 3.0%, p = .003). The effect on immune activation in the off-ART cohort was likely confounded by increased plasma HIV-1 RNA during chloroquine administration (median 0.29 log10 increase, p < .001). Transcriptional analyses in the off-ART cohort showed decreased expression of interferon-stimulated genes in 5 of 10 chloroquine-treated participants and modest decreases in CD38 and CCR5 RNAs in all chloroquine-treated participants. Chloroquine modestly reduced immune activation in ART-treated HIV-infected participants. Clinical Trials Registry Number: NCT00819390.
A Formal Semantics of the Core DOM in Isabelle/HOL

At its core, the Document Object Model (DOM) defines a tree-like data structure for representing documents in general and HTML documents in particular. It is the heart of any modern web browser. Formalizing the key concepts of the DOM is a prerequisite for the formal reasoning over client-side JavaScript programs and for the analysis of security concepts in modern web browsers. We present a formalization of the core DOM, with focus on the node-tree and the operations defined on node-trees, in Isabelle/HOL. We use the formalization to verify the functional correctness of the most important functions defined in the DOM standard. Moreover, our formalization is extensible, i.e., can be extended without the need of re-proving already proven properties and executable, i.e., we can generate executable code from our specification.
Alendronate delivery on amino modified mesoporous bioactive glass scaffolds to enhance bone regeneration in osteoporosis rats

Abstract The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Nowadays, alendronate (AL) are orally administrated for osteoporosis due to the inhibition of bone resorption. However, systemic administration of AL is characterized by extremely low bioavailability and high toxicity. In this study, the amino-modified mesoporous bioactive glass scaffolds (N-MBGS) were fabricated by a simple powder processing technique as a novel drug-delivery system for AL. The effects of AL on the osteogenic differentiation of bone mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX) were first estimated. The loading efficiency and release kinetics of AL on N-MBGS were investigated in vitro and the osteogenesis of AL-loaded N-MBGS in rat calvarial defect model was detected by micro-CT measurements and the histological assay. Our results revealed that proper concentration of AL significantly promoted osteogenic differentiation of rBMSCs-OVX. The amount and delivery rate of AL were greatly improved through amino modification. Additionally, scaffolds with AL showed better bone formation in vivo, especially for the N-MBGS group. Our results suggest that the novel amino-modified MBGS are promising drug-delivery system for osteoporotic bone defect repairing or regeneration. The experimental schematic of the novel amino-modified MBGS as a promising drug-delivery system for osteoporotic bone regeneration. Graphical Abstract
Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride

Liver fibrosis is a common scarring response to all forms of chronic liver injury and is always associated with inflammation that contributes to fibrogenesis. Although a variety of cell populations infiltrate the liver during inflammation, it is generically clear that CD8 T lymphocytes promote while natural killer (NK) cells inhibit liver fibrosis. However, the role of invariant natural killer T (iNKT) cells, which are abundant in the liver, in hepatic fibrogenesis, remains obscure. Here we show that iNKT‐deficient mice are more susceptible to carbon tetrachloride (CCl4)‐induced acute liver injury and inflammation. The protective effect of naturally activated iNKT in this model is likely mediated via suppression of the proinflammatory effect of activated hepatic stellate cells. Interestingly, strong activation of iNKT through injection of iNKT activator α‐galactosylceramide (α‐GalCer) accelerates CCl4‐induced acute liver injury and fibrosis. In contrast, chronic CCl4 administration induces a similar degree of liver injury in iNKT‐deficient and wild‐type mice, and only a slightly higher grade of liver fibrosis in iNKT‐deficient mice than wild‐type mice 2 weeks but not 4 weeks after CCl4 injection, although iNKT cells are able to kill activated stellate cells. An insignificant role of iNKT in chronic liver injury and fibrosis may be attributable to hepatic iNKT cell depletion. Finally, chronic α‐GalCer treatment had little effect on liver injury and fibrosis, which is attributable to iNKT tolerance after α‐GalCer injection. Conclusion: Natural activation of hepatic iNKT cells inhibits, whereas strong activation of iNKT cells by α‐GalCer accelerates CCl4‐induced acute liver injury, inflammation, and fibrosis. During chronic liver injury, hepatic iNKT cells are depleted and play a role in inhibiting liver fibrosis in the early stage but not the late stage of fibrosis. (HEPATOLOGY 2009.)
A Reflection on Child and Infant Mortality in Selected South Asian Countries

Objectives: This study aims to explore the infant and child mortality rates in relation to (i) a range of conventional covariates including household characteristics, literacy rates, cultural and social factors, treatment method, mother’s history like preceding birth interval between children & multiple births and provision of facilities like electricity, safe water and sanitation etc. (ii) some policy variables like health facilities related to cesarean section and women empowerment related to health which is a very nascent concept in public health literature. Methods: The study design is cross-sectional which exploits the latest Demographic Health Surveys from the selected South Asian countries including Pakistan (2012), Bangladesh (2011) India (2012) and Nepal (2011). The Cox’s proportional hazard model is used to establish the factors that affect the infant and child mortality. Conclusion: The results of the study support the argument of health interventions in the region that should be designed to reach the most undeserved: women and children. More specifically, we recommend particular focus on better cesarean section method of delivery and women empowerment in health related issues.
How I manage patients with cold agglutinin disease

Cold agglutinin disease (CAD) is an uncommon autoimmune haemolytic anaemia in which a well‐defined, clonal low‐grade lymphoproliferative disorder of the bone marrow results in erythrocyte destruction mediated by the classical complement pathway. The pathogenesis, clinical features and diagnostic criteria are reviewed. Although anaemia is mild in some patients, approximately one‐third of untreated patients have a haemoglobin level of ≤80 g/l, and about 50% have been considered transfusion dependent for shorter or longer periods. Therapy has improved greatly during the last 15 years. Mild disease can be managed by avoidance of cold and adequate precautions in specific situations, without drug therapy. Corticosteroids should not be used to treat CAD. Patients requiring pharmacological therapy should be considered for prospective trials. Outside clinical studies, the rituximab‐bendamustine combination or rituximab monotherapy is recommended in the first line, depending on individual patient characteristics. Second‐line options are rituximab‐fludarabine in fit patients or, although less strongly documented, a bortezomib‐based regimen. Therapies targeting the classical complement pathway are promising, and the complement C1s inhibitor, BIVV009, has shown favourable results in preliminary studies.
Evidence for an Anti-Inflammatory Loop Centered on Polymorphonuclear Leukocyte Formyl Peptide Receptor 2/Lipoxin A4 Receptor and Operative in the Inflamed Microvasculature

The importance of proresolving mediators in the overall context of the resolution of acute inflammation is well recognized, although little is known about whether these anti-inflammatory and proresolving molecules act in concert. In this article, we focused on lipoxin A4 (LXA4) and annexin A1 (AnxA1) because these two very different mediators converge on a single receptor, formyl peptide receptor type 2 (FPR2/ALX). Addition of LXA4 to human polymorphonuclear leukocytes (PMNs) provoked a concentration- and time-dependent mobilization of AnxA1 onto the plasma membrane, as determined by Western blotting and flow cytometry analyses. This property was shared by another FPR2/ALX agonist, antiflammin-2, and partly by fMLF or peptide Ac2-26 (an AnxA1 derivative that can activate all three members of the human FPR family). An FPR2/ALX antagonist blocked AnxA1 mobilization activated by LXA4 and antiflammin-2. Analysis of PMN degranulation patterns and phospho-AnxA1 status suggested a model in which the two FPR2/ALX agonists mobilize the cytosolic (and not the granular) pool of AnxA1 through an intermediate phosphorylation step. Intravital microscopy investigations of the inflamed mesenteric microvasculature of wild-type and AnxA1−/− mice revealed that LXA4 provoked leukocyte detachment from the postcapillary venule endothelium in the former (>50% within 10 min; p < 0.05), but not the latter genotype (∼15%; NS). Furthermore, recruitment of Gr1+ cells into dorsal air-pouches, inflamed with IL-1β, was significantly attenuated by LXA4 in wild-type, but not AnxA1−/−, mice. Collectively, these data prompt us to propose the existence of an endogenous network in anti-inflammation centered on PMN AnxA1 and activated by selective FPR2/ALX agonists.
Cardiac Tagging with Breath‐Hold Cine MRI

A method is presented for measuring myocardial deformation in a breath‐hold with tagged cine MRI. Tagged cine images of human hearts are obtained in arbitrary oblique planes on a standard imager with as few as four heartbeats. The scan time has been reduced 16‐ to 64‐fold from previous techniques. © 1992 Academic Press,Inc.
Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Contro

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).
Une approche de la stabilisation interne par l ’ analyse algébrique III . Sur une forme générale des contrôleurs stabilisants basée sur le rang stable

Résumé— Ce papier a pour but de donner une vue générale des différents résultats récemment obtenus sur la stabilisation interne des systèmes linéaires de dimension infinie. On s’attachera à faire ressortir les principales idées plus que la technique utilisée. En particulier, nous donnerons des conditions nécessaires et suffissantes à la stabilisation interne et à l’existence de factorisations doublement copremières faibles ou fortes. Nous caractériserons alors les algèbres de systèmes SISO stables A sur lesquelles tout système − défini par une matrice de transfert à coefficients dans le corps de fractions K = Q(A) de A − est stabilisable de manière interne ou admet des factorisations doublement copremières faibles ou fortes.
Cognitive consequences and central nervous system injury following treatment for childhood leukemia.

OBJECTIVES To determine the relationship between membrane damage and intellectual and academic abilities in children with acute lymphoblastic leukemia (ALL) and pilot test a math intervention for children with ALL who were affected. DATA SOURCES Research studies and review articles. CONCLUSIONS Despite the prophylactic central nervous system (CNS) treatment for long-term disease-free survival, many children with ALL subsequently experience declines in intellectual and academic skills. IMPLICATIONS FOR NURSING PRACTICE Improving academic abilities in children who have received CNS treatment is of high priority and may have longlasting implications on quality of life.
Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned.

AIM to evaluate the influence of gluten consumption on celiac disease development and to describe its natural history in the Spanish cohort of the European PreventCD study. METHODS prospective multi-center double blind study of 225 children that were followed up from birth. All cases were HLA-DQ2/HLA-DQ8 positive with a 1st degree relative with celiac disease and were followed up in three centers from Madrid, Reus and Valencia. Gluten intake was determined between four and ten months according to the protocol. Gluten intake was ad libitum between eleven and 36 months and was prospectively quantified by means of dietary records. Clinical visits and specific antibody analysis for celiac disease were performed periodically. RESULTS twenty-six cases were diagnosed, all had a positive biopsy and serology; 21 had gastrointestinal symptoms and five were asymptomatic. In addition, 2,565 food records were analyzed and statistically significant differences (p < 0.001) were found with regard to gluten consumption among the three centers, although not between celiac and non-celiac children (p = 0.025). The HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes had a relative risk of 4.7 (95% CI: 0.80-27.55; p = 0.08), which was higher than for the rest of genotypes. Female gender also had a relative risk that was five times higher than that for males. CONCLUSIONS the amount of gluten intake between 11 and 36 months or the duration of breast feeding were not risk factors for the development of CD in the Spanish population. The HLA genotype and gender were the most relevant associated factors. In this at-risk group, the disease presented before two years of age in the majority of the cases with a weak clinical expression.
Cultural Attitudes, Parental Aspirations, and Socioeconomic Influence on Post-Primary School Selection in Northern Ireland

ABSTRACT This research considers implications of planned reform of the education system in Northern Ireland for school choice and travel behavior. The school system is currently segregated on the basis of religion and academic ability at age 11. Discrete Choice Models based on a Stated Preference experiment included in a program of parental surveys yielded insights into likely responses of parents to both current options and potential reforms. Surprisingly, most parents would not be adverse to the removal of religious segregation from schools while availability of free school transport is not a significant factor in the school choice process. Aspirations of academic quality are higher among more affluent parents.
Patients’ and Community Leaders’ Perceptions Regarding Conducting Health Behavior Research in a Diverse, Urban Clinic Specializing in Rheumatic Diseases

Background: Disparities in the incidence, prevalence, severity, care, and outcomes for rheumatic diseases exist among racial and ethnic groups compared with White Americans. Objective: This paper describes a community-based participatory research (CBPR) approach engaging researchers, community leaders, and patients in purposeful dialogues related to the implementation of health behavior research in an urban rheumatic disease clinic. Methods: Seven focused discussions were led in either English or Spanish. Discussions were audiotaped and transcribed verbatim. Results: Six community leaders and nine patients participated in the seven scheduled focused discussions. Transcripts uncovered five major themes that assisted with study design: trust, patient–provider relationship, study implementation suggestions, decreased functional capacity, and access to healthcare. Conclusions: Engaging community partners and patients in informal and formal discussions from early phases of research design through implementation, followed by systematic application of these insights, may serve to accelerate the potential for translation from findings into improved clinical practice and optimal outcomes.
Mothers' Parenting Style and the Development of Children's Theory of Mind

Objective: To explore the relationship between mothers' parenting style and the development of children's theory of mind. Methods:Fifty-three 3-5-year-olds children and their mothers were involved in this study. Children were asked to finish four TOM tasks and mothers to complete parenting style questionnaire separately. Children and their parents took part in the parent-child play together and their interactions were video-recorded. Results: mothers' parenting style questionnaire indicated that children's TOM achievement was positively correlated to mothers' severe punishing after control of age(r=0.39, P0.01), whereas the result of observation showed a significantly posi-tive correlation between children's TOM achievement and mothers' warmth and understanding(r=0.40, P0.01). Conclusion:Children's TOM achievement is significantly related to their mothers' severe punishing,warmth and understanding.
Fecal Indicator Bacteria in Subsurface Drain Water Following Swine Manure Application

Appropriate manure application parameters are necessary to maximize nutrient utilization by plants from manure while minimizing water pollution potential. This study focused on the movement of bacteria to receiving tile drains following swine manure application. Specifically, the impacts of different manure application regimes on fecal coliform (FC), Enterococcus (EN), and Escherichia coli (EC) densities in subsurface tile drain water were examined for three years. Manure treatments, including fall, spring, and late winter application at a recommended rate of 168 kg N ha-1 (1X) and at 336 kg N ha-1 (2X) were compared with a non-manure treatment where commercial urea-ammonium nitrate (UAN) was applied. Results indicate that flow-weighted average and maximum observed EN and EC levels in tile water were significantly higher where manure had been applied during late winter at the 2X rate versus the UAN and fall treatments. Levels of FC were highly variable, and the spring injection 1X treatment yielded the highest flow-weighted average and maximum tile water FC levels. Results of this study suggest that manure broadcast onto frozen ground may lead to significantly elevated EN and EC levels in tile water in similar environments, especially when applied in excess of crop nutrient requirements.