bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells
Authors: Björkström Niklas K. , Béziat Vivien , Cichocki Frank , Liu Lisa L. , Levine Jeffrey , Larsson Stella , Koup Richard A. , Anderson Stephen K. , Ljunggren Hans-Gustaf , Malmberg Karl-Johan 
Published: September 2012

AbstractEpistatic interactions between killer cell immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands have important implications for reproductive success, antiviral immunity, susceptibility to autoimmune conditions and cancer, as well as for graft-versus-leukemia reactions in settings of allogeneic stem cell transplantation. Although CD8 T cells are known to acquire KIRs when maturing from naive to terminally differentiated cells, little information is available about the constitution of KIR repertoires on human CD8 T cells. Here, we have performed a high-resolution analysis of KIR expression on CD8 T cells. The results show that most CD8 T cells possess a restricted KIR expression pattern, often dominated by a single activating or inhibitory KIR. Furthermore, the expression of KIR, and its modulation of CD8 T-cell function, was independent of expression of self-HLA class I ligands. Finally, despite similarities in the stochastic regulation of KIRs by the bidirectional proximal promoter, the specificity of inhibitory KIRs on CD8 T cells was often distinct from that of natural killer cells in the same individual. The results provide new insight into the formation of KIR repertoires on human T cells.
A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation
Authors: Li Chunfu , Wu Xuedong , Feng Xiaoqing , He Yuelin , Liu Huaying , Pei Fuyu , Liao Jianyu , He Lan , Shi Lei , Li Na , Liu Qiujun , Liu Shiting , Chen Geyu , Su Qingxia , Ren Yuqiong , Wang Yanhua , Tan Wanxia 
Published: September 2012

AbstractWe used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with β-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TM-free survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat β-thalassemia patients in the absence of MSDs.
How I treat HHV8/KSHV-related diseases in posttransplant patients
Authors: Riva Giovanni , Luppi Mario , Barozzi Patrizia , Forghieri Fabio , Potenza Leonardo 
Published: September 2012

Abstract
Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) primary infection and/or reactivations are associated with uncommon and sometimes fatal, neoplastic, and non-neoplastic diseases. HHV8-related clinical manifestations notably range from Kaposi sarcoma (KS) to either primary effusion lymphoma or multicentric Castleman disease B-cell malignancies, and from polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow failure and peripheral cytopenias, associated or not with hemophagocytic syndromes, and to acute hepatitis syndromes. We reviewed the patient series reported in the literature and summarized clinical management aspects, in terms of diagnosis, follow-up, and treatment. We described typical clinical presentations and histopathologic diagnostic features of these diseases, and we discussed the role of HHV8-specific serologic, molecular, and immunologic assays, particularly focusing on recent data from HHV8-specific T-cell monitoring in posttransplantation KS patients. We finally discussed actual therapeutic options, namely, the reduction or discontinuation of immunosuppressive therapy or the switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to antineoplastic chemotherapy, along with the use of antiherpesvirus agents as prophylactic or therapeutic measures, and treatment with rituximab in posttrans-plantation multicentric Castleman disease patients and non-neoplastic HHV8-associated syndromes.
SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival
Authors: Lasho Terra L. , Jimma Thitina , Finke Christy M. , Patnaik Mrinal , Hanson Curtis A. , Ketterling Rhett P. , Pardanani Animesh , Tefferi Ayalew 
Published: September 2012

Abstract
Among spliceosome component mutations, those involving SF3B1 are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼ 75% incidence) and SRSF2 in chronic myelomonocytic leukemia (∼ 28% incidence). We recently reported on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32 (17%) harbored SRSF2 monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03). SRSF2 mutations were associated with shortened overall (P < .01) and leukemia-free (P < .01) survival; the adverse effect on survival was independent of DIPSS-plus (P = .01; HR = 1.9; 95% CI, 1.1-3.0) and IDH mutations (P < .01; HR = 2.3; 95% CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor outcome.
Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression
Authors: Adhikary Sabina , Kocieda Virginia P. , Yen Jui-Hung , Tuma Ronald F. , Ganea Doina 
Published: September 2012

Abstract
Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and autoimmune disease and CNS injury models results in significant attenuation of clinical disease, and reduction of inflammatory mediators. Previous studies reported that CB2R signaling also reduces leukocyte migration. Migration of dendritic cells (DCs) to various sites is required for their activation and for the initiation of adaptive immune responses. Here, we report for the first time that CB2R signaling affects DC migration in vitro and in vivo, primarily through the inhibition of matrix metalloproteinase 9 (MMP-9) expression. Reduced MMP-9 production by DCs results in decreased migration to draining lymph nodes in vivo and in vitro in the matrigel migration assay. The effect on Mmp-9 expression is mediated through CB2R, resulting in reduction in cAMP levels, subsequent decrease in ERK activation, and reduced binding of c-Fos and c-Jun to Mmp-9 promoter activator protein 1 sites. We postulate that, by dampening production of MMP-9 and subsequent MMP-9–dependent DC migration, cannabinoids contribute to resolve acute inflammation and to reestablish homeostasis. Selective CB2R agonists might be valuable future therapeutic agents for the treatment of chronic inflammatory conditions by targeting activated immune cells, including DCs.
The Saccharomyces cerevisiae Hot1p regulated gene YHR087W (HGI1) has a role in translation upon high glucose concentration stress
Authors: Gomar-Alba M , Jiménez-Martí E , del Olmo M 
Published: September 2012

Abstract

Background
While growing in natural environments yeasts can be affected by osmotic stress provoked by high glucose concentrations. The response to this adverse condition requires the HOG pathway and involves transcriptional and posttranscriptional mechanisms initiated by the phosphorylation of this protein, its translocation to the nucleus and activation of transcription factors. One of the genes induced to respond to this injury is YHR087W. It encodes for a protein structurally similar to the N-terminal region of human SBDS whose expression is also induced under other forms of stress and whose deletion determines growth defects at high glucose concentrations.

Results
In this work we show that YHR087W expression is regulated by several transcription factors depending on the particular stress condition, and Hot1p is particularly relevant for the induction at high glucose concentrations. In this situation, Hot1p, together to Sko1p, binds to YHR087W promoter in a Hog1p-dependent manner. Several evidences obtained indicate Yhr087wp’s role in translation. Firstly, and according to TAP purification experiments, it interacts with proteins involved in translation initiation. Besides, its deletion mutant shows growth defects in the presence of translation inhibitors and displays a slightly slower translation recovery after applying high glucose stress than the wild type strain. Analyses of the association of mRNAs to polysome fractions reveals a lower translation in the mutant strain of the mRNAs corresponding to genes GPD1, HSP78 and HSP104.

Conclusions
The data demonstrates that expression of Yhr087wp under high glucose concentration is controlled by Hot1p and Sko1p transcription factors, which bind to its promoter. Yhr087wp has a role in translation, maybe in the control of the synthesis of several stress response proteins, which could explain the lower levels of some of these proteins found in previous proteomic analyses and the growth defects of the deletion strain.
Novel variants of HMW glutenin subunits from Aegilops section Sitopsis species in relation to evolution and wheat breeding
Authors: Jiang Qian-Tao , Ma Jian , Wei Yu-Ming , Liu Ya-Xi , Lan Xiu-Jin , Dai Shou-Fen , Lu Zhen-Xiang , Zhao Shan , Zhao Quan-Zhi , Zheng You-Liang 
Published: September 2012

Abstract

Background
High molecular weight glutenin subunits (HMW-GSs), encoded by the genes at Glu-1 loci in wheat and its related species, are significant in the determination of grain processing quality. However, the diversity and variations of HMW-GSs are relatively low in bread wheat. More interests are now focused on wheat wild relatives in Triticeae. The genus Aegilops represents an important germplasm for novel HWM-GSs and other useful genes for wheat genetic improvement.

Results
Six novel Glu-1 alleles and HMW-GSs were identified and characterized from three species of Aegilops section Sitopsis (S genome). Both open reading frames (ORFs) and promoter regions of these Glu-1 alleles were sequenced and characterized. The ORFs of Sitopsis Glu-1 genes are approximately 2.9 kb and 2.3 kb for x-type and y-type subunits, respectively. Although the primary structures of Sitopsis HMW-GSs are similar to those of previously reported ones, all six x-type or y-type subunits have the large fragment insertions. Our comparative analyses of the deduced amino acid sequences verified that Aegilops section Sitopsis species encode novel HMW-GSs with their molecular weights larger than almost all other known HMW-GSs. The Glu-1 promoter sequences share the high homology among S genome. Our phylogenetic analyses by both network and NJ tree indicated that there is a close phylogenetic evolutionary relationship of x-type and y-type subunit between S and D genome.

Conclusions
The large molecular weight of HMW-GSs from S genome is a unique feature identified in this study. Such large subunits are resulted from the duplications of repetitive domains in Sitopsis HMW-GSs. The unequal crossover events are the most likely mechanism of variations in glutenin subunits. The S genome-encoded subunits, 1Dx2.2 and 1Dx2.2* have independent origins, although they share similar evolutionary mechanism. As HMW-GSs play a key role in wheat baking quality, these large Sitopsis glutenin subunits can be used as special genetic resources for wheat quality improvement.
Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures
Authors: Lerario Alberto , Bonfiglio Serena , Sormani MariaPia , Tettamanti Andrea , Marktel Sarah , Napolitano Sara , Previtali Stefano , Scarlato Marina , Natali-Sora MariaGrazia , Mercuri Eugenio , Bresolin Nereo , Mongini Tiziana , Comi Giancarlo , Gatti Roberto , Ciceri Fabio , Cossu Giulio , Torrente Yvan 
Published: September 2012

Abstract

Background
The aim of this study was to perform a longitudinal assessment using Quantitative Muscle Testing (QMT) in a cohort of ambulant boys affected by Duchenne muscular dystrophy (DMD) and to correlate the results of QMT with functional measures. This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or thee 6-min walk test (6MWT).

Methods
This is a single centre, prospective, non-randomised, study assessing QMT using the Kin Com® 125 machine in a study cohort of 28 ambulant DMD boys, aged 5 to 12 years. This cohort was assessed longitudinally over a 12 months period of time with 3 monthly assessments for QMT and with assessment of functional abilities, using the NSAA and the 6MWT at baseline and at 12 months only. QMT was also used in a control group of 13 healthy age-matched boys examined at baseline and at 12 months.

Results
There was an increase in QMT over 12 months in boys below the age of 7.5 years while in boys above the age of 7.5 years, QMT showed a significant decrease. All the average one-year changes were significantly different than those experienced by healthy controls. We also found a good correlation between quantitative tests and the other measures that was more obvious in the stronger children.

Conclusion
Our longitudinal data using QMT in a cohort of DMD patients suggest that this could be used as an additional tool to monitor changes, providing additional information on segmental strength.
Study Protocol. IDUS – Instrumental delivery & ultrasound. A multi-centre randomised controlled trial of ultrasound assessment of the fetal head position versus standard care as an approach to prevent morbidity at instrumental delivery
Authors: Murphy Deirdre J , Burke Gerard , Montgomery Alan A , Ramphul Meenakshi ,   The IDUS StudyGroup
Published: September 2012

Abstract

Background
Instrumental deliveries are commonly performed in the United Kingdom and Ireland, with rates of 12 – 17% in most centres. Knowing the exact position of the fetal head is a pre-requisite for safe instrumental delivery. Traditionally, diagnosis of the fetal head position is made on transvaginal digital examination by delineating the suture lines of the fetal skull and the fontanelles. However, the accuracy of transvaginal digital examination can be unreliable and varies between 20% and 75%. Failure to identify the correct fetal head position increases the likelihood of failed instrumental delivery with the additional morbidity of sequential use of instruments or second stage caesarean section. The use of ultrasound in determining the position of the fetal head has been explored but is not part of routine clinical practice.

Methods/Design
A multi-centre randomised controlled trial is proposed. The study will take place in two large maternity units in Ireland with a combined annual birth rate of 13,500 deliveries. It will involve 450 nulliparous women undergoing instrumental delivery after 37 weeks gestation. The main outcome measure will be incorrect diagnosis of the fetal head position. A study involving 450 women will have 80% power to detect a 10% difference in the incidence of inaccurate diagnosis of the fetal head position with two-sided 5% alpha.

Discussion
It is both important and timely to evaluate the use of ultrasound to diagnose the fetal head position prior to instrumental delivery before routine use can be advocated. The overall aim is to reduce the incidence of incorrect diagnosis of the fetal head position prior to instrumental delivery and improve the safety of instrumental deliveries.

Trial registration
Current Controlled Trials ISRCTN72230496
Respiratory viral infections in children with asthma: do they matter and can we prevent them?
Authors: Ahanchian Hamid , Jones Carmen M , Chen Yueh-sheng , Sly Peter D 
Published: September 2012

Abstract

Background
Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma.

Discussion
While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use.

Summary
Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.
Language barrier and its relationship to diabetes and diabetic retinopathy
Authors: Zheng Yingfeng , Lamoureux Ecosse L , Chiang Pei-Chia Peggy , Anuar Ainur Rahman , Ding Jie , Wang Jie Jin , Mitchell Paul , Tai E-Shyong , Wong Tien Y 
Published: September 2012

Abstract

Background
Language barrier is an important determinant of health care access and health. We examined the associations of English proficiency with type-2 diabetes (T2DM) and diabetic retinopathy (DR) in Asian Indians living in Singapore, an urban city where English is the predominant language of communication.

Methods
This was a population-based, cross-sectional study. T2DM was defined as HbA1c ≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal photographs were graded for the severity of DR including vision-threatening DR (VTDR). Presenting visual impairment (VI) was defined as LogMAR visual acuity > 0.30 in the better-seeing eye. English proficiency at the time of interview was assessed.

Results
The analyses included 2,289 (72.1%) English-speaking and 885 (27.9%) Tamil- speaking Indians. Tamil-speaking Indians had significantly higher prevalence of T2DM (46.2 vs. 34.7%, p < 0.001) and, among those with diabetes, higher prevalence of DR (36.0 vs. 30.6%, p < 0.001), VTDR (11.0 vs. 6.5%, p < 0.001), and VI (32.4 vs. 14.6%) than English speaking Indians. Oaxaca decomposition analyses showed that the language-related discrepancies (defined as the difference in prevalence between persons speaking different languages) in T2DM, DR, and VTDR could not be fully explained by socioeconomic measures.

Conclusions
In an English dominant society, Tamil-speaking Indians are more likely to have T2DM and diabetic retinopathy. Social policies and health interventions that address language-related health disparities may help reduce the public health impact of T2DM in societies with heterogeneous populations.
Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum field isolates
Authors: Rutvisuttinunt Wiriya , Chaorattanakawee Suwanna , Tyner Stuart D , Teja-isavadharm Paktiya , Se Youry , Yingyuen Kritsanai , Chaichana Panjaporn , Bethell Delia , Walsh Douglas S , Lon Chanthap , Fukuda Mark , Socheat Duong , Noedl Harald , Schaecher Kurt , Saunders David L 
Published: September 2012

Abstract

Background
Apparent emerging artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia requires development of practical tools to monitor for resistant parasites. Although in vitro anti-malarial susceptibility tests are widely used, uncertainties remain regarding interpretation of P. falciparum field isolate values.

Methods
Performance parameters of the W2 P. falciparum clone (considered artemisinin “sensitive”) were evaluated as a reference for the HRP-2 immediate ex vivo assay. Variability in W2 IC50s was assessed, including intra- and inter-assay variability among and between technicians in multiple experiments, over five freeze-thaw cycles, over five months of continuous culture, and before and after transport of drug-coated plates to remote field sites. Nominal drug plate concentrations of artesunate (AS) and dihydroartemisinin (DHA) were verified by LC-MS analysis. Plasmodium falciparum field isolate IC50s for DHA from subjects in an artemisinin-resistant area in Cambodia were compared with W2 susceptibility.

Results
Plate drug concentrations and day-to-day technical assay performance among technicians were important sources of variability for W2 IC50s within and between assays. Freeze-thaw cycles, long-term continuous culture, and transport to and from remote sites had less influence. Despite variability in W2 susceptibility, the median IC50s for DHA for Cambodian field isolates were higher (p <0.0001) than the W2 clone (3.9 nM), both for subjects with expected (less than 72 hours; 6.3 nM) and prolonged (greater or equal to 72 hours; 9.6 nM) parasite clearance times during treatment with artesunate monotherapy.

Conclusion
The W2 reference clone improved the interpretability of field isolate susceptibility from the immediate ex vivo HRP-2 assay from areas of artemisinin resistance. Methods to increase the reproducibility of plate coating may improve overall assay interpretability and utility.