bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet‐Induced Obesity Enhances TRPV1‐Mediated Neurovascular Reactions in the Dura Mater
Authors: Marics Balázs , Peitl Barna , Pázmándi Kitti , Bácsi Attila , Németh József , Oszlács Orsolya , Jancsó Gábor , Dux Mária 
Published: January 2017

ObjectiveExploring the pathophysiological changes in transient receptor potential vanilloid 1 (TRPV1) receptor of the trigeminovascular system in high‐fat, high‐sucrose (HFHS) diet‐induced obesity of experimental animals.BackgroundClinical and experimental observations suggest a link between obesity and migraine. Accumulating evidence indicates that metabolic and immunological alterations associated with obesity may potentially modulate trigeminovascular functions. A possible target for obesity‐induced pathophysiological changes is the TRPV1/capsaicin receptor which is implicated in the pathomechanism of headaches in a complex way.MethodsMale Sprague‐Dawley rats were fed a regular (n = 25) or HFHS diet (n = 26) for 20 weeks. At the end of the dietary period, body weight of the animals was normally distributed in both groups and it was significantly higher in animals on HFHS diet. Therefore, experimental groups were regarded as control and HFHS diet‐induced obese groups. Capsaicin‐induced changes in meningeal blood flow and release of calcitonin gene‐related peptide (CGRP) from dural trigeminal afferents were measured in control and obese rats. The distribution of TRPV1‐ and CGRP‐immunoreactive meningeal sensory nerves was also compared in whole mount preparations of the dura mater. Metabolic parameters of the animals were assessed by examining glucose and insulin homeostasis as well as plasma cytokine concentrations.ResultsHFHS diet was accompanied by reduced food consumption and greater fluid and energy intakes in addition to increased body weight of the animals. HFHS diet increased fasting blood glucose and insulin concentrations as well as levels of circulating proinflammatory cytokines interleukin‐1β and interleukin‐6. In obese animals, dural application of the archetypal TRPV1 agonist capsaicin resulted in significantly augmented vasodilatory and vasoconstrictor responses as compared to controls. Diet‐induced obesity was also associated with enhanced basal and capsaicin‐induced CGRP release from meningeal afferents ex vivo. Except for minor morphological changes, the distribution of dural TRPV1‐ and CGRP‐immunoreactive afferents was similar in control and obese animals.ConclusionsOur results suggest that obesity induced by long‐term HFHS diet results in sensitization of the trigeminovascular system. Changes in TRPV1‐mediated vascular reactions and CGRP release are pathophysiological alterations that may be of relevance to the enhanced headache susceptibility of obese individuals.
The clinicopathologic significance of lymphocyte subsets in acute myeloid leukemia
Authors: Alcasid M. , Ma L. , Gotlib J. R. , Arber D. A. , Ohgami R. S. 
Published: January 2017

SummaryIntroductionWhile the role of the immune system in altering and modulating the progression of solid tumors is well studied, the impact of the immune system on the outcome and progression of hematolymphoid neoplasms is still poorly understood.MethodsHere, we report a retrospective study detailing our analysis of 130 patients with acute myeloid leukemia (AML), with flow cytometry immunophenotypic evaluation of major lymphocyte subsets including B cells, T cells, and NK cells.ResultsOur study identifies differential signatures of lymphocyte subsets pertaining to distinct subcategories of AML, and prognostic correlations in patients. In multivariate analysis, NK cells (specifically CD56+/CD16+ NK cells at a cutoff of ≥5%) were found to be an independent indicator of improved overall and disease‐free survival; cytogenetic risk was also shown to be critical in stratifying patients with AML.ConclusionsIn total, we demonstrate that in AML, the subset distribution of immune system lymphocytes is nonrandom, and suggest an important role for distinct lymphocyte subsets, particularly NK cells, in this disease.
Simultaneous detection of 45 fusion genes in leukemia by dual‐color fluorescence real‐time PCR
Authors: Zheng Z. , Zhang P. , He G. , Liao K. , Wang Z. , Pan J. , Du K. , Du J. , Li B.‐A. 
Published: January 2017

SummaryIntroductionDetection of recurrent genetic abnormalities is of great significance for a refined diagnosis and assessment of prognosis in leukemia. Conventional nested reverse transcription PCR is labor intensive and time‐consuming.MethodsWe have developed a novel dual‐color TaqMan probe‐based real‐time PCR method for the simultaneous screening of 45 fusion transcripts in 12 parallel reactions. The method was tested and validated with cell lines carrying known fusion transcripts and patient samples.ResultsA multiplex real‐time PCR method was successfully developed for rapid detection of 45 fusion genes and validated for 15 of the more commonly detected fusion genes. Intra‐assay reproducibility assessed for the most frequent rearrangements ranged from 0.41% to 0.74% for the coefficient of variation (CV) of cycle threshold (Ct) and the interassay reproducibility ranged from 1.62% to 2.83% in five separate experiments. The lowest detection limit for the translocations tested ranged between 1 : 16 000 and 1 : 32 000. Validation of the method with 213 patient samples showed 100% specificity and excellent consistence with conventional nested RT‐PCR.ConclusionOverall, we believe that this method is easily applicable, cost‐effective, and clinically useful for a rapid screening of fusion genes in the initial diagnostic phase of leukemia. Its use can also be extended to the monitoring of minimal residual disease.
Molecular basis of pyruvate kinase deficiency among Tunisians: description of new mutations affecting coding and noncoding regions in the PKLR gene
Authors: Jaouani M. , Manco L. , Kalai M. , Chaouch L. , Douzi K. , Silva A. , Macedo S. , Darragi I. , Boudriga I. , Chaouachi D. , Fitouri Z. , Van Wijk R. , Ribeiro M. L. , Abbes S. 
Published: January 2017

SummaryIntroductionPyruvate kinase (PK) deficiency is one of the most common hereditary nonspherocytic hemolytic anemias worldwide with clinical manifestations ranging from mild to severe hemolysis. However, investigation of this enzymopathy is lacking in Tunisia. We report here a pioneer investigation of PK deficiency among Tunisian cases referred to our laboratory for biological analysis of unknown cause of hemolytic anemia.MethodsTwo hundred and fifty‐three patients with unknown cause of hemolytic anemia have been addressed to our laboratory in order to investigate for red blood cells genetic disorders. Red cell enzyme activities were measured by standard methods, and molecular analysis was performed by DNA sequencing. The interpretation of mutation effect and the molecular modeling were performed by using specific software.ResultsSix different PKLR mutations were found (c.966‐1G>T; c.965+1G>A; c.721G>T; c.1163C>A; c.1456C>T; c.1537T>A), among which four are described for the first time. Genotype–phenotype correlations for the novel missense mutations were investigated by three‐dimensional structure analysis.ConclusionThis study provides important data of PK deficiency among Tunisians. It might be followed by a large neonatal screening to determine the spectrum of PK mutations and identify potential deficient patients for an early medical follow‐up.
Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1
Authors: Kwong Peter D. , Chuang Gwo‐Yu , DeKosky Brandon J. , Gindin Tatyana , Georgiev Ivelin S. , Lemmin Thomas , Schramm Chaim A. , Sheng Zizhang , Soto Cinque , Yang An‐Suei , Mascola John R. , Shapiro Lawrence 
Published: January 2017

SummaryNumerous antibodies have been identified from HIV‐1‐infected donors that neutralize diverse strains of HIV‐1. These antibodies may provide the basis for a B cell‐mediated HIV‐1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics‐based approach to understand the genetic and immunologic processes controlling the development of HIV‐1‐neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next‐generation sequencing of B‐cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6). We also incorporated large‐scale robotic analyses of serum neutralization to identify and quantify neutralizing antibodies in donor cohorts (Antibodyomics3). Statistical analyses furnish another layer of insight (Antibodyomics5), with physical characteristics of antibodies and their targets through molecular dynamics simulations (Antibodyomics7) and free energy perturbation analyses (Antibodyomics8) providing information‐rich output. Functional interrogation of individual antibodies (Antibodyomics9) and synthetic antibody libraries (Antibodyomics10) also yields multi‐dimensional data by which to understand and improve antibodies. Antibodyomics, described here, thus comprise resolution‐enhancing tools, which collectively embody an information‐driven discovery engine aimed toward the development of effective B cell‐based vaccines.
Native‐like Env trimers as a platform for HIV‐1 vaccine design
Authors: Sanders Rogier W. , Moore John P. 
Published: January 2017

SummaryWe describe the development and potential use of various designs of recombinant HIV‐1 envelope glycoprotein trimers that mimic the structure of the virion‐associated spike, which is the target for neutralizing antibodies. The goal of trimer development programs is to induce broadly neutralizing antibodies with the potential to intervene against multiple circulating HIV‐1 strains. Among the topics we address are the designs of various constructs; how native‐like trimers can be produced and purified; the properties of such trimers in vitro and their immunogenicity in various animals; and the immunization strategies that may lead to the eventual elicitation of broadly neutralizing antibodies. In summary, native‐like trimers are a now a platform for structure‐ and immunology‐based design improvements that could eventually yield immunogens of practical value for solving the long‐standing HIV‐1 vaccine problem.
Identification and specificity of broadly neutralizing antibodies against HIV
Authors: McCoy Laura E. , Burton Dennis R. 
Published: January 2017

SummaryBeginning in 2009, studies of the humoral responses of HIV‐positive individuals have led to the identification of scores, if not hundreds, of antibodies that are both broadly reactive and potently neutralizing. This development has provided renewed impetus toward an HIV vaccine and led directly to the development of novel immunogens. Advances in identification of donors with the most potent and broad anti‐HIV serum neutralizing responses were crucial in this effort. Equally, development of methods for the rapid generation of human antibodies from these donors was pivotal. Primarily these methods comprise single B‐cell culture coupled to high‐throughput neutralization screening and flow cytometry‐based sorting of single B cells using HIV envelope protein baits. In this review, the advantages and disadvantages of these methodologies are discussed in the context of the specificities targeted by individual antibodies and the need for further improvements to evaluate HIV vaccine candidates.
B‐cell responses to HIV infection
Authors: Moir Susan , Fauci Anthony S. 
Published: January 2017

SummaryThe induction of neutralizing antibodies directed against the human immunodeficiency virus (HIV) has received considerable attention in recent years, in part driven by renewed interest and opportunities for antibody‐based strategies for prevention such as passive transfer of antibodies and the development of preventive vaccines, as well as immune‐based therapeutic interventions. Advances in the ability to screen, isolate, and characterize HIV‐specific antibodies have led to the identification of a new generation of potent broadly neutralizing antibodies (bNAbs). The majority of these antibodies have been isolated from B cells of chronically HIV‐infected individuals with detectable viremia. In this review, we provide insight into the phenotypic and functional attributes of human B cells, with a focus on HIV‐specific memory B cells and plasmablasts/cells that are responsible for sustaining humoral immune responses against HIV. We discuss the abnormalities in B cells that occur in HIV infection both in the peripheral blood and lymphoid tissues, especially in the setting of persisting viremia. Finally, we consider the opportunities and drawbacks of intensively interrogating antibodies isolated from HIV‐infected individuals to guide strategies aimed at developing effective antibody‐based vaccine and therapeutic interventions for HIV.
Systems serology for evaluation of HIV vaccine trials
Authors: Ackerman Margaret E. , Barouch Dan H. , Alter Galit 
Published: January 2017

SummaryThe scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non‐human primates and humans points to a role for polyclonal vaccine‐induced antibody responses in protection from infection. These candidate vaccines, despite employing disparate viral vectors and immunization strategies, consistently identify a role for functional or non‐traditional antibody activities as correlates of immunity. However, the precise mechanism(s) of action of these “binding” antibodies, their specific characteristics, and their ability to be selectively induced and/or potentiated to result in complete protection merits parallel investigation to neutralizing antibody‐based vaccine design approaches. Ultimately, while neutralizing and functional antibody‐based vaccine strategies need not be mutually exclusive, defining the specific characteristics of “protective” functional antibodies may provide a target immune profile to potentially induce more robust immunity against HIV. Specifically, one approach to guide the development of functional antibody‐based vaccine strategies, termed “systems serology”, offers an unbiased and comprehensive approach to systematically survey humoral immune responses, capturing the array of functions and humoral response characteristics that may be induced following vaccination with high resolution. Coupled to machine learning tools, large datasets that explore the “antibody‐ome” offer a means to step back from anticipated correlates and mechanisms of protection and toward a more fundamental understanding of coordinated aspects of humoral immune responses, to more globally differentiate among vaccine candidates, and most critically, to identify the features of humoral immunity that distinguish protective from non‐protective responses. Overall, the systematic serological approach described here aimed at broadly capturing the enormous biodiversity in antibody profiles that may emerge following vaccination, complements the existing cutting edge tools in the cellular immunology space that survey vaccine‐induced polyfunctional cellular activity by flow cytometry, transcriptional profiling, epigenetic, and metabolomic analysis to offer a means to develop both a more nuanced and a more complete understanding of correlates of protection to support the design of functional vaccine strategies.
Survivors Remorse: antibody‐mediated protection against HIV‐1
Authors: Lewis George K. , Pazgier Marzena , DeVico Anthony L. 
Published: January 2017

SummaryIt is clear that antibodies can play a pivotal role in preventing the transmission of HIV‐1 and large efforts to identify an effective antibody‐based vaccine to quell the epidemic. Shortly after HIV‐1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody‐based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV‐1 variants can lead to broadly neutralizing antibodies in some infected individuals. This observation drives an intensive effort to identify a vaccine to elicit broadly neutralizing antibodies. In contrast, there has been less systematic study of antibody specificities that must rely mainly or exclusively on other protective mechanisms, although non‐human primate (NHP) studies as well as the RV144 vaccine trial indicate that non‐neutralizing antibodies can contribute to protection. Here we propose a novel strategy to identify new epitope targets recognized by these antibodies for which viral escape is unlikely or impossible.
Use of broadly neutralizing antibodies for HIV‐1 prevention
Authors: Pegu Amarendra , Hessell Ann J. , Mascola John R. , Haigwood Nancy L. 
Published: January 2017

SummaryAntibodies have a long history in antiviral therapy, but until recently, they have not been actively pursued for HIV‐1 due to modest potency and breadth of early human monoclonal antibodies (MAbs) and perceived insurmountable technical, financial, and logistical hurdles. Recent advances in the identification and characterization of MAbs with the ability to potently neutralize diverse HIV‐1 isolates have reinvigorated discussion and testing of these products in humans, since new broadly neutralizing MAbs (bnMAbs) are more likely to be effective against worldwide strains of HIV‐1. In animal models, there is abundant evidence that bnMAbs can block infection in a dose‐dependent manner, and the more potent bnMAbs will allow clinical testing at infusion doses that are practically achievable. Moreover, recent advances in antibody engineering are providing further improvements in MAb potency, breadth, and half‐life. This review summarizes the current state of the field of bnMAb protection in animal models as well as a review of variables that are critical for antiviral activity. Several bnMAbs are currently in clinical testing, and we offer perspectives on their use as pre‐exposure prophylaxis (PrEP), potential benefits beyond sterilizing immunity, and a discussion of future approaches to engineer novel molecules.
Safety and efficacy of intramuscular human placenta‐derived mesenchymal stromal‐like cells (cenplacel [PDA‐002]) in patients who have a diabetic foot ulcer with peripheral arterial disease
Authors: Wu Stephanie C , Pollak Richard , Frykberg Robert G , Zhou Wei , Karnoub Maha , Jankovic Vladimir , Fischkoff Steven A , Chitkara Denesh 
Published: January 2017

AbstractThe objective of this study was to examine the safety of cenplacel (PDA‐002) in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU). Cenplacel is a mesenchymal‐like cell population derived from full‐term human placenta. This phase 1, dose‐escalation study investigated cenplacel in diabetic patients with chronic DFUs (Wagner grade 1 or grade 2) and PAD [ankle‐brachial index (ABI) >0·5 and ≤0·9], enrolled sequentially into each of four dose cohorts (3 × 106, 10 × 106, 30 × 106 and 100 × 106 cells; administered intramuscularly on study days 1 and 8 in combination with standard of care). Overall, cenplacel was well tolerated in all 15 patients in the study. Before enrollment, nine patients had an ulcer for ≥6 months and 11 had an ABI of 0·7–0·85. No patient met dose‐limiting toxicity criteria and no treatment‐related serious adverse events were reported. There was preliminary evidence of ulcer healing in seven patients (five complete; two partial) within 3 months of cenplacel treatment, and circulating endothelial cell levels (a biomarker of vascular injury in PAD) were decreased within 1 month. Cenplacel was generally safe and well tolerated in patients with chronic DFUs and PAD. Outcomes from this study informed the doses, endpoints, biomarkers and patient population for an ongoing phase 2 trial.
Healthy food choice: Survey results from Iranian consumers toward antibiotic‐free chicken
Authors: Rahnama Hassan , Fadaei Mehdi , Baghersalimi Saeed 
Published: January 2017

AbstractDemand for healthy food is increasing in Iran. Although demand for these foods has increased, the real benefits and purchasing patterns are not known. The purpose of this study is to identify factors affecting consumer choice behavior toward antibiotic‐free chicken, and examines whether there are significant differences in importance of these factors between consumers with different outlooks. Logistic regression, chi‐square, and Friedman test were applied to assess collected data by a questionnaire survey. The results indicated that perception, awareness, motivation, social factors, and lifestyle had significant influence on the choice of antibiotic‐free chicken and demographic factors had no influence on it. Among effective factors, perception, and motivation have the most and least effect on choice of antibiotic‐free chicken, respectively.Practical applicationsThese results are relevant to sensory scientists and healthy foods producers, especially antibiotic‐free chicken producers are interested to know how different factors will be able to impact on consumers' choice behavior. There is less information in the literature about consumer choice behavior toward antibiotic‐free chicken in Iran and another country. A better understanding of consumer choice behavior can be beneficial to develop this kind of product, and help poultry industry activists to encourage consumer to buy healthy products. The study showed that consumers' perception including high quality, appropriate packaging, cleanness of store, and credible brand are the most influential factors on consumer choice behavior. The researchers' findings might suggest the importance of social factors and raise of awareness as another important factors through consumers approach.
Protective effects of breastfeeding against acute respiratory tract infections and diarrhoea: Findings of a cohort study
Authors: Raheem Raheema Abdul , Binns Colin W , Chih Hui J 
Published: January 2017

AimThe objective of this paper is to identify associations between breastfeeding and acute respiratory tract infections (ARTIs) and diarrhoea.MethodsA cohort of 458 mothers was recruited at the antenatal clinics at Indira Gandhi Memorial and Abdul Rahman Dhon Kaleyfaanu Hospitals. Mothers were interviewed ‘face‐to‐face’ at 36 weeks of gestation and at 1, 3 and 6 months after delivery. The questionnaires included demographic information about parents, infant feeding methods and breastfeeding duration. The number of episodes of ARTIs and diarrhoea was also recorded. Ethics approval was obtained from the National Research Committee of the Maldives and Curtin University Human Research Ethics Committee. Descriptive, univariate, logistic and survival analyses were used to assess the effects of breastfeeding on infant ARTIs and diarrhoea.ResultsThe partial, predominant and exclusive breastfeeding rates at 1 month were 98.9, 67.6 and 26.9%, respectively. The risk of acquiring ARTIs is significantly reduced when the infants were predominantly breastfed for 3 months (adjusted odds ratio (OR): 0.56, 95% of adjusted OR: 0.34–0.94) and 6 months (adjusted OR: 0.45, 95% of adjusted OR: 0.24–0.84). The risk of getting diarrhoea is significantly reduced even when the babies were partially breastfed for 6 months (adjusted OR): 0.31, 95% of adjusted OR: 0.11–0.90). Kaplan Meier curves demonstrated that the risk lowers with longer duration of breastfeeding.ConclusionBreastfeeding need to be promoted because the risk of infant morbidity is negatively associated with the duration of breastfeeding.