bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allo-HLA–reactive T cells inducing graft-versus-host disease are single peptide specific
Authors: Amir Avital L. , van der Steen Dirk M. , Hagedoorn Renate S. , Kester Michel G. D. , van Bergen Cornelis A. M. , Drijfhout Jan W. , de Ru Arnoud H. , Falkenburg J. H. Frederik , van Veelen Peter A. , Heemskerk Mirjam H. M. 
Published: October 2011

AbstractT-cell alloreactivity directed against non–self-HLA molecules has been assumed to be less peptide specific than conventional T-cell reactivity. A large variation in degree of peptide specificity has previously been reported, including single peptide specificity, polyspecificity, and peptide degeneracy. Peptide polyspecificity was illustrated using synthetic peptide-loaded target cells, but in the absence of confirmation against endogenously processed peptides this may represent low-avidity T-cell reactivity. Peptide degeneracy was concluded based on recognition of Ag-processing defective cells. In addition, because most investigated alloreactive T cells were in vitro activated and expanded, the previously determined specificities may have not been representative for alloreactivity in vivo. To study the biologically relevant peptide specificity and avidity of alloreactivity, we investigated the degree of peptide specificity of 50 different allo-HLA–reactive T-cell clones which were activated and expanded in vivo during GVHD. All but one of the alloreactive T-cell clones, including those reactive against Ag-processing defective T2 cells, recognized a single peptide allo-HLA complex, unique for each clone. Down-regulation of the expression of the recognized Ags using silencing shRNAs confirmed single peptide specificity. Based on these results, we conclude that biologically relevant alloreactivity selected during in vivo immune response is peptide specific.
Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation
Authors: Jiang Shan , Li Chaoran , Olive Virginie , Lykken Erik , Feng Feng , Sevilla Jose , Wan Ying , He Lin , Li Qi-Jing 
Published: October 2011

Abstract
Mir-17-92 encodes 6 miRNAs inside a single polycistronic transcript, the proper expression of which is critical for early B-cell development and lymphocyte homeostasis. However, during the T-cell antigen response, the physiologic function of endogenous miR-17-92 and the roles of the individual miRNAs remain elusive. In the present study, we functionally dissected the miR-17-92 cluster and revealed that miR-17 and miR-19b are the key players controlling Th1 responses through multiple coordinated biologic processes. These include: promoting proliferation, protecting cells from activation-induced cell death, supporting IFN-γ production, and suppressing inducible regulatory T-cell differentiation. Mechanistically, we identified Pten (phosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGFβRII and the novel target CREB1. Because of its vigorous control over the Th1 cell–inducible regulatory T cell balance, the loss of miR-17-92 in CD4 T cells results in tumor evasion. Our results suggest that miR-19b and miR-17 could be harnessed to enhance the efficacy of T cell–based tumor therapy.
Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells
Authors: Obermajer Nataša , Muthuswamy Ravikumar , Lesnock Jamie , Edwards Robert P. , Kalinski Pawel 
Published: October 2011

AbstractDendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) show opposing roles in the immune system. In the present study, we report that the establishment of a positive feedback loop between prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2), the key regulator of PGE2 synthesis, represents the determining factor in redirecting the development of CD1a+ DCs to CD14+CD33+CD34+ monocytic MDSCs. Exogenous PGE2 and such diverse COX2 activators as lipopolysaccharide, IL-1β, and IFNγ all induce monocyte expression of COX2, blocking their differentiation into CD1a+ DCs and inducing endogenous PGE2, IDO1, IL-4Rα, NOS2, and IL-10, typical MDSC-associated suppressive factors. The addition of PGE2 to GM-CSF/IL-4–supplemented monocyte cultures is sufficient to induce the MDSC phenotype and cytotoxic T lymphocyte (CTL)–suppressive function. In accordance with the key role of PGE2 in the physiologic induction of human MDSCs, the frequencies of CD11b+CD33+ MDSCs in ovarian cancer are closely correlated with local PGE2 production, whereas the cancer-promoted induction of MDSCs is strictly COX2 dependent. The disruption of COX2-PGE2 feedback using COX2 inhibitors or EP2 and EP4 antagonists suppresses the production of MDSC-associated suppressive factors and the CTL-inhibitory function of fully developed MDSCs from cancer patients. The central role of COX2-PGE2 feedback in the induction and persistence of MDSCs highlights the potential for its manipulation to enhance or suppress immune responses in cancer, autoimmunity, or transplantation.
Detecting genomic regions associated with a disease using variability functions and Adjusted Rand Index
Authors: Badescu Dunarel , Boc Alix , Diallo Abdoulaye Baniré , Makarenkov Vladimir 
Published: October 2011

Abstract

Background
The identification of functional regions contained in a given multiple sequence alignment constitutes one of the major challenges of comparative genomics. Several studies have focused on the identification of conserved regions and motifs. However, most of existing methods ignore the relationship between the functional genomic regions and the external evidence associated with the considered group of species (e.g., carcinogenicity of Human Papilloma Virus). In the past, we have proposed a method that takes into account the prior knowledge on an external evidence (e.g., carcinogenicity or invasivity of the considered organisms) and identifies genomic regions related to a specific disease.

Results and conclusion
We present a new algorithm for detecting genomic regions that may be associated with a disease. Two new variability functions and a bipartition optimization procedure are described. We validate and weigh our results using the Adjusted Rand Index (ARI), and thus assess to what extent the selected regions are related to carcinogenicity, invasivity, or any other species classification, given as input. The predictive power of different hit region detection functions was assessed on synthetic and real data. Our simulation results suggest that there is no a single function that provides the best results in all practical situations (e.g., monophyletic or polyphyletic evolution, and positive or negative selection), and that at least three different functions might be useful. The proposed hit region identification functions that do not benefit from the prior knowledge (i.e., carcinogenicity or invasivity of the involved organisms) can provide equivalent results than the existing functions that take advantage of such a prior knowledge. Using the new algorithm, we examined the Neisseria meningitidis FrpB gene product for invasivity and immunologic activity, and human papilloma virus (HPV) E6 oncoprotein for carcinogenicity, and confirmed some well-known molecular features, including surface exposed loops for N. meningitidis and PDZ domain for HPV.
In search of the genetic footprints of Sumerians: a survey of Y-chromosome and mtDNA variation in the Marsh Arabs of Iraq
Authors: Al-Zahery Nadia , Pala Maria , Battaglia Vincenza , Grugni Viola , Hamod Mohammed A , Kashani Baharak Hooshiar , Olivieri Anna , Torroni Antonio , Santachiara-Benerecetti Augusta S , Semino Ornella 
Published: October 2011

Abstract

Background
For millennia, the southern part of the Mesopotamia has been a wetland region generated by the Tigris and Euphrates rivers before flowing into the Gulf. This area has been occupied by human communities since ancient times and the present-day inhabitants, the Marsh Arabs, are considered the population with the strongest link to ancient Sumerians. Popular tradition, however, considers the Marsh Arabs as a foreign group, of unknown origin, which arrived in the marshlands when the rearing of water buffalo was introduced to the region.

Results
To shed some light on the paternal and maternal origin of this population, Y chromosome and mitochondrial DNA (mtDNA) variation was surveyed in 143 Marsh Arabs and in a large sample of Iraqi controls. Analyses of the haplogroups and sub-haplogroups observed in the Marsh Arabs revealed a prevalent autochthonous Middle Eastern component for both male and female gene pools, with weak South-West Asian and African contributions, more evident in mtDNA. A higher male than female homogeneity is characteristic of the Marsh Arab gene pool, likely due to a strong male genetic drift determined by socio-cultural factors (patrilocality, polygamy, unequal male and female migration rates).

Conclusions
Evidence of genetic stratification ascribable to the Sumerian development was provided by the Y-chromosome data where the J1-Page08 branch reveals a local expansion, almost contemporary with the Sumerian City State period that characterized Southern Mesopotamia. On the other hand, a more ancient background shared with Northern Mesopotamia is revealed by the less represented Y-chromosome lineage J1-M267*. Overall our results indicate that the introduction of water buffalo breeding and rice farming, most likely from the Indian sub-continent, only marginally affected the gene pool of autochthonous people of the region. Furthermore, a prevalent Middle Eastern ancestry of the modern population of the marshes of southern Iraq implies that if the Marsh Arabs are descendants of the ancient Sumerians, also the Sumerians were most likely autochthonous and not of Indian or South Asian ancestry.
A metagenomic study of methanotrophic microorganisms in Coal Oil Point seep sediments
Authors: Håvelsrud Othilde Elise , Haverkamp Thomas HA , Kristensen Tom , Jakobsen Kjetill S , Rike Anne Gunn 
Published: October 2011

Abstract

Background
Methane oxidizing prokaryotes in marine sediments are believed to function as a methane filter reducing the oceanic contribution to the global methane emission. In the anoxic parts of the sediments, oxidation of methane is accomplished by anaerobic methanotrophic archaea (ANME) living in syntrophy with sulphate reducing bacteria. This anaerobic oxidation of methane is assumed to be a coupling of reversed methanogenesis and dissimilatory sulphate reduction. Where oxygen is available aerobic methanotrophs take part in methane oxidation. In this study, we used metagenomics to characterize the taxonomic and metabolic potential for methane oxidation at the Tonya seep in the Coal Oil Point area, California. Two metagenomes from different sediment depth horizons (0-4 cm and 10-15 cm below sea floor) were sequenced by 454 technology. The metagenomes were analysed to characterize the distribution of aerobic and anaerobic methanotrophic taxa at the two sediment depths. To gain insight into the metabolic potential the metagenomes were searched for marker genes associated with methane oxidation.

Results
Blast searches followed by taxonomic binning in MEGAN revealed aerobic methanotrophs of the genus Methylococcus to be overrepresented in the 0-4 cm metagenome compared to the 10-15 cm metagenome. In the 10-15 cm metagenome, ANME of the ANME-1 clade, were identified as the most abundant methanotrophic taxon with 8.6% of the reads. Searches for particulate methane monooxygenase (pmoA) and methyl-coenzyme M reductase (mcrA), marker genes for aerobic and anaerobic oxidation of methane respectively, identified pmoA in the 0-4 cm metagenome as Methylococcaceae related. The mcrA reads from the 10-15 cm horizon were all classified as originating from the ANME-1 clade.

Conclusions
Most of the taxa detected were present in both metagenomes and differences in community structure and corresponding metabolic potential between the two samples were mainly due to abundance differences.
The results suggests that the Tonya Seep sediment is a robust methane filter, where taxa presently dominating this process could be replaced by less abundant methanotrophic taxa in case of changed environmental conditions.
A proposed method to investigate reliability throughout a questionnaire
Authors: Wentzel-Larsen Tore , Norekvål Tone M , Ulvik Bjørg , Nygård Ottar , Pripp Are H 
Published: October 2011

Abstract

Background
Questionnaires are used extensively in medical and health care research and depend on validity and reliability. However, participants may differ in interest and awareness throughout long questionnaires, which can affect reliability of their answers. A method is proposed for "screening" of systematic change in random error, which could assess changed reliability of answers.

Methods
A simulation study was conducted to explore whether systematic change in reliability, expressed as changed random error, could be assessed using unsupervised classification of subjects by cluster analysis (CA) and estimation of intraclass correlation coefficient (ICC). The method was also applied on a clinical dataset from 753 cardiac patients using the Jalowiec Coping Scale.

Results
The simulation study showed a relationship between the systematic change in random error throughout a questionnaire and the slope between the estimated ICC for subjects classified by CA and successive items in a questionnaire. This slope was proposed as an awareness measure - to assessing if respondents provide only a random answer or one based on a substantial cognitive effort. Scales from different factor structures of Jalowiec Coping Scale had different effect on this awareness measure.

Conclusions
Even though assumptions in the simulation study might be limited compared to real datasets, the approach is promising for assessing systematic change in reliability throughout long questionnaires. Results from a clinical dataset indicated that the awareness measure differed between scales.
Rare gallbladder adenomyomatosis presenting as atypical cholecystitis: case report
Authors: Lin Sheng-Hong , Chang Feng-Yee , Yang Ya-Sung , Jin Jong-Shiaw , Chen Teng-Wei 
Published: October 2011

Abstract

Background
Gallbladder adenomyomatosis is a benign condition characterized by hyperplastic change in the gallbladder wall and overgrowth of the mucosa because of an unknown cause. Patients with gallbladder adenomyomatosis usually present with abdominal pain. However, we herein describe a case of a patient with gallbladder adenomyomatosis who did not present with abdominal pain, but with only fever.

Case presentation
A 34-year-old man presented to our hospital with a fever. No abdominal discomfort was declared. His physical examination showed no abnormalities. Ultrasound of the abdomen revealed thickness of the gallbladder. Acute cholecystitis was diagnosed. The fever persisted even after 1 week of antibiotic therapy. Magnetic resonance imaging of the abdomen showed gallbladder adenomyomatosis with intramural Rokitansky-Aschoff sinuses. Exploratory laparotomy with cholecystectomy was performed. The fever recovered and no residual symptoms were reported at the 3-year follow-up.

Conclusions
Gallbladder adenomyomatosis can present with fever as the only symptom. Although the association between gallbladder adenomyomatosis and malignancy has yet to be elucidated, previous reports have shown a strong association between gallbladder carcinoma and a subtype of gallbladder adenomyomatosis. Surgical intervention remains the first-choice treatment for patients with gallbladder adenomyomatosis.
Development of a short form of Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint: a case control study
Authors: Haubois Gladys , Annweiler Cédric , Launay Cyrille , Fantino Bruno , de Decker Laure , Allali Gilles , Beauchet Olivier 
Published: October 2011

Abstract

Background
Primary care physicians need a brief and accurate screening test of dementia. The objective of this study was to determine whether a short form of Mini-Mental State Examination (SMMSE) was as accurate as the Mini-Mental State Examination (MMSE) in screening dementia.

Methods
Based on case control design study, SMMSE and MMSE were assessed in 184 community-dwelling older adults (mean age 81.3 ± 6.5 years, 71.7% women) with memory complaint sent by their primary care physician to a memory clinic. Included participants were separated into two groups: cognitively healthy individuals and demented individuals.

Results
The trade-off between sensitivity and specificity of the SMMSE for clinically diagnosed dementia was 4. Based on the cut-off value ≤ 4 for SMMSE and a cut-off value ≤ 24 for MMSE, the sensitivity of both tests was similar (89.5% for SMMSE versus 90.0% for MMSE), whereas the specificity, the positive predictive values (PPV) and the negative predictive values (NPV) were higher for SMMSE compared to MMSE (85.4 versus 75.5% for specificity; 95.5% versus 92.8% for PPV; 70.0 versus 68.9 for NPV). The positive and negative Likehood Ratio (LR) of SMMSE were higher than those of MMSE (respectively, 6.1 versus 3.7; 8.1 versus 7.7). In addition, odds ratio (OR) for dementia was higher for the SMMSE compared to the MMSE (OR = 49.8 with 95% confident interval (CI) [18.0; 137.8] versus OR = 28.6 with 95% CI [11.6; 70.3]).

Conclusions
SMMSE seems to be an efficient short screening test for dementia among community-dwelling older adults with a memory complaint. Further research is needed to confirm its predictive values among unselected primary care older patients.
High sensitivity of an ELISA kit for detection of the gamma-isoform of 14-3-3 proteins: usefulness in laboratory diagnosis of human prion disease
Authors: Matsui Yuki , Satoh Katsuya , Miyazaki Toshiaki , Shirabe Susumu , Atarashi Ryuichiro , Mutsukura Kazuo , Satoh Akira , Kataoka Yasufumi , Nishida Noriyuki 
Published: October 2011

Abstract

Background
The gamma-isoform of the 14-3-3 protein (14-3-3 gamma) is expressed in neurons, and could be a specific marker for neuronal damage. This protein has been reported as a detectable biomarker, especially in the cerebrospinal fluid (CSF) of Creutzfeldt-Jakob disease (CJD) patients by Western blotting (WB) or enzyme-linked immunosorbent assays (ELISAs). Western blotting for 14-3-3 gamma is not sensitive, and the reported data are conflicting among publications. An ELISA specific for 14-3-3 gamma is not available.

Methods
CJD patients (n = 114 sporadic CJD patients, 7 genetic CJD, and 3 iatrogenic CJD) and 99 patients with other neurodegenerative diseases were examined in this study. The CSF samples obtained were analyzed by Western blotting for 14-3-3 gamma, and by ELISA for total tau protein. We evaluated the sensitivity and specificity of the newly developed sandwich ELISA for 14-3-3 gamma.

Results
The cut-off value of the 14-3-3 gamma ELISA was > 1, 683 AU/ml; and sensitivity was 95.2%, with 72.7% specificity. This specificity was the same for the total tau protein ELISA. Seven CJD cases were negative by WB but positive using the 14-3-3 gamma ELISA, indicating that the ELISA is more sensitive. All 21 cases of early stage CJD could be diagnosed using a combination of the 14-3-3γ ELISA and diffusion weighted MR imaging (DWI-MRI).

Conclusion
The 14-3-3 gamma ELISA was more sensitive than conventional WB, and was useful for laboratory diagnosis of CJD, similar to the ELISA for the tau protein. Using DWI-MRI and these ELISA tests on CSF, diagnosis of CJD will be possible even at early stages of the disease.
Striving to be prepared for the painful: Management strategies following a family member's diagnosis of advanced cancer
Authors: Sjolander Catarina , Hedberg Berith , Ahlstrom Gerd 
Published: October 2011

Abstract

Background
Cancer has consequences not only for the sick person but also for those who have a close relationship with that person. Greater knowledge about how family members manage the situation in the period immediately following the diagnosis means greater opportunity to provide the best possible support for the family. The purpose of this study was to explore management strategies that family members use when the patient is in the early stage of treatment for advanced cancer.

Methods
Twenty family members of cancer patients were included in the study shortly after the diagnosis. The patients had been diagnosed 8-14 weeks earlier with advanced lung cancer or gastrointestinal cancer. The data were collected in interviews with family members and subjected to qualitative latent content analysis. Through the identification of similarities and dissimilarities in the units of meaning, abstraction into codes and sub-themes became possible. The sub-themes were then brought together in one overarching theme.

Results
The overall function of management strategies is expressed in the theme Striving to be prepared for the painful. The family members prepare themselves mentally for the anticipated tragedy. Family relationships become increasingly important, and family members want to spend all their time together. They try to banish thoughts of the impending death and want to live as normal a life as possible. It becomes important to family members to live in the present and save their energy for the time when they will need it the most. How participants handle their worries, anxiety and sadness can be categorized into seven sub-themes or management strategies: Making things easier in everyday life, Banishing thoughts about the approaching loss, Living in the present, Adjusting to the sick person's situation, Distracting oneself by being with others, Shielding the family from grief, and Attempting to maintain hope.

Conclusions
The findings revealed that the family members have their own resources for handling the early stage of the cancer trajectory in an acceptable way. There is a need for longitudinal studies to generate knowledge for designing evidence-based intervention programmes that can prevent future ill-health in these vulnerable family members.