julilili42/papers huggingface dataset:
Single and dual energy attenuation correction in PET/CT in the presence of iodine based contrast agents
2008-04-24

In present positron emission tomography (PET)/computed tomography (CT) scanners, PET attenuation correction is performed by relying on the information given by a single CT scan. The scaling of the linear attenuation coefficients from CT x‐ray energy to PET gamma energy is prone to errors especially in the presence of CT contrast agents. Attenuation correction based upon two CT scans at different energies but performed at the same time and patient position should reduce such errors and therefore improve the accuracy of the reconstructed PET images at the cost of introduced additional noise. Such CT scans could be provided by future PET/CT scanners that have either dual source CT or energy sensitive CT. Three different dual energy scaling methods for attenuation correction are introduced and assessed by measurements with a modified NEMA 1994 phantom with different CT contrast agent concentrations. The scaling is achieved by differentiating between (1) Compton and photoelectric effect, (2) atomic number and density, or (3) water‐bone and water‐iodine scaling schemes. The scaling method (3) is called hybrid dual energy computed tomography attenuation correction (hybrid DECTAC). All three dual energy scaling methods lead to a reduction of contrast agent artifacts with respect to single energy scaling. The hybrid DECTAC method resulted in PET images with the weakest artifacts. Both, the hybrid DECTAC and Compton/photoelectric effect scaling resulted also in images with the lowest PET background variability. Atomic number/density scaling and Compton/photoelectric effect scaling had problems to correctly scale water, hybrid DECTAC scaling and single energy scaling to correctly scale Teflon. Atomic number/density scaling and hybrid DECTAC could be generalized to reduce these problems.
Immunohistochemical localization of nanog and Oct4 in stem cell compartments of human sacrococcygeal teratomas
2008-04-24

Aims: To study the range of differentiation and presence of cells positive for stem cell markers in 20 sacrococcygeal teratomas (SCTs) which were consecutively operated on between 1990 and 2000 in the Department of Paediatric Surgery in Tübingen, Germany. Methods and results: Preserved paraffin‐embedded material was re‐evaluated. In addition to tissues of various organs, caudal organ structures not described before were identified, such as colon with pancreas originating from colonic crypts, Fallopian tube and vaginal epithelia. The derivation of the latter was confirmed by Müllerian duct specific CA125 and CA19‐9 antibodies. The expression of stem cell markers was studied with antibodies against nanog, Oct4, SSEA‐4, nestin and subtype M3 muscarinic receptors. Cells positive for these markers were encountered in immature end buds and capillary sprouts, and as single cells in neural tissue, gonadal structures, hairs and in the stem cell niches of differentiated epithelia. Conclusions: Our data indicate that SCTs of the newborn arise from remnants of the epiblast‐like tail bud blastema and demonstrate that they contain cells positive for embryonic stem cell markers and may represent a novel source for human embryonic stem cells.
Heterogeneity of Breast Cancer Associations with Five Susceptibility Loci by Clinical and Pathological Characteristics
2008-04-25

A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults
2008-04-25

Abstract BACKGROUND. Mesenchymal chondrosarcoma (MCS) is a rare tumor with a strong tendency toward late recurrences leading to reported 10‐year survival rates below 50%. The recommended treatment is resection with wide margins; the effectiveness of chemo‐ and radiotherapy remain poorly defined. As reports about MCS in young patients are scarce, treatment and outcomes of children/adolescents/young adults in the CWS and COSS studies were investigated. METHODS. Since 1977, 15 of &gt;7000 CWS and COSS patients ≤25 years had a confirmed diagnosis of MCS. RESULTS. The median age was 16.6 (range, 1–25) and median follow‐up 9.6 years (range, 1–22). Four MCS were osseous and 11 extraosseous. All but 1 patient had nonmetastatic disease. Tumor sites were head/neck (n = 6), paravertebral (n = 3), pelvis (n = 3), limbs (n = 2), and kidney (n = 1). All tumors were resected, but only 8 completely. Thirteen individuals received chemotherapy, 6 were irradiated. Actuarial 10‐year event‐free and overall survival rates were 53% and 67%, respectively. Four recurrences occurred, all within 4 years from diagnosis (3 local, 1 combined; 2 of these in irradiated patients). One of these patients survived after surgery and radiation for local recurrence. Seven of 8 patients whose tumors were completely resected during primary treatment, but only 4 of 7 patients with incomplete surgery survived disease‐free. CONCLUSIONS. This series of 15 MCS differs from others: the median age was young, most tumors were extraosseous, most patients received chemotherapy, and the outcome was better than published. Despite long‐term follow‐up, characteristic late metastatic recurrences were not observed. Treating MCS according to standard multimodal soft tissue/bone sarcoma regimens is proposed. Cancer 2008. © 2008 American Cancer Society.
Review: Familial Parkinson's disease – genetics, clinical phenotype and neuropathology in relation to the common sporadic form of the disease
2008-04-25

The identification of the first gene in familial Parkinson's disease (PD) only 10 years ago was a major step in the understanding of the molecular mechanisms in neurodegeneration. Alpha‐synuclein aggregation was not only recognized as a key event in neurodegeneration in patients carrying mutations in this gene, but it turned out to be the most consistent marker to define Lewy body pathology also in non‐heritable idiopathic PD (IPD). Subsequent comprehensive pathoanatomical studies of IPD brains led to a novel concept of an ascending pathological process in variable stages that are reflected by alpha‐synuclein aggregation at specific predilection sites. To date, more than seven genes are known to cause familial PD. The fact that these genetic forms of Parkinsonism present with clinical features indistinguishable from IPD, but may display neuropathological features that are not consistent with IPD, underscores the need of a more differentiated approach to familial and sporadic forms of Parkinsonism. Indeed, in distinct populations, mutations in one single gene were found to cause the disease in up to 40% of patients formerly described as ‘idiopathic’ cases. These findings indicate that IPD, as defined by a late‐onset disorder with no (apparent) genetic contribution, is part of a clinical syndrome that becomes more and more heterogeneous in terms of aetiology, with overlapping clinical and pathoanatomical features. Thus in the present review, we discuss clues from familial PD to our understanding of the molecular pathogenesis of neurodegeneration with special consideration of the variable clinical and neuropathological aspects.
Functional similarities between the P1 component and alpha oscillations
2008-04-25

Abstract The present study attempts to demonstrate functional similarities between the P1 component of event‐related potentials and alpha oscillations that are predicted by the ‘alpha inhibition‐timing’ hypothesis. On the basis of findings showing that the frequency characteristic of the P1 component lies in the alpha range and that alpha oscillation is functionally associated with inhibition, we predict that the P1 component also reflects inhibitory processes. This hypothesis is tested in two experiments, a spatial‐cuing task and a visual‐semantic categorization task. The results of the cuing task demonstrate that in a similar way as alpha power, the P1 component is larger over task‐irrelevant ipsilateral sites. For the categorization task, we found that the P1 component, in a similar way to alpha oscillations, is larger for task‐irrelevant, distorted pictures. We conclude that the P1 component may be generated at least in part by evoked alpha oscillations and reflects inhibition in the sense of suppressing task‐irrelevant processes.
Hyperattenuating bone marrow abnormalities in myeloma patients using whole-body non-enhanced low-dose MDCT: correlation with haematological parameters
2008-04-25

We aimed to establish the role of hyperattenuating medullary abnormalities detected by whole-body non-enhanced low-dose multidetector CT (WBLD-MDCT) in multiple myeloma (MM) patients referred for primary evaluation. 50 consecutive patients with untreated Stage I (n(I) = 11), Stage II (n(II) = 10) and Stage III (n(III) = 29) MM underwent WBLD-MDCT for staging. The number and size of osteolysis, as well as haematologic parameters including paraprotein and beta2-microglobulin levels, were assessed and related to the number, size and density of medullary abnormalities assumed to represent myeloma involvement. Bone marrow abnormalities were found in 2/11 (18%) Stage I, 6/10 (60%) Stage II and 20/29 (69%) Stage III myeloma patients, and did not parallel the incidence of osteolysis. Patients with medullary lesions had higher levels of immunoglobulin A (median, 4730 mg dl(-1) vs 1520 mg dl(-1)), light-chain proteinuria (median, 690 mg dl(-1) vs 214 mg dl(-1)) and IgG paraprotein (median, 3270 mg dl(-1) vs 2610 mg dl(-1)) compared with patients without medullary lesions. In patients with medullary abnormalities, levels of serum beta2-microglobulin were significantly higher than in patients without detectable marrow infiltrates (median, 4.3 mg dl(-1) vs 2.4 mg dl(-1); p = 0.0015). In conclusion, medullary abnormalities visualized by WBLD-MDCT are encountered in all stages of myeloma, including cases without osteolysis. They are associated with significantly elevated serum levels of paraprotein (reflecting tumour mass) and beta2-microglobulin, a prospective prognostic marker for myeloma. The nature and possible prognostic significance of medullary abnormalities detected by WBLD-MDCT therefore warrants further investigation.
Functional analysis of human CNGA3 mutations associated with colour blindness suggests impaired surface expression of channel mutants A3R427C and A3R563C
2008-04-25

Abstract Mutations in the CNGA3 gene have been associated with complete and incomplete forms of total colour blindness (achromatopsia), a disorder characterized by reduced visual acuity, lack of colour discrimination, photophobia and nystagmus. CNGA3 encodes the A‐subunit of the cone photoreceptor cyclic nucleotide‐gated (CNG) channel, an essential component of the phototransduction cascade. Here we report the identification of three new CNGA3 mutations in patients with achromatopsia. To assess the pathogenicity of these newly identified and four previously reported mutations, mutant CNGA3 channels were heterologously expressed in a human embryonic kidney cell line (HEK293 cells) and functionally analysed using calcium imaging. Channels with the mutations R427C and R563C showed a response in imaging experiments and were subsequently characterized in‐depth with the patch‐clamp technique. The mutant channels were analysed as homooligomers and also as heterooligomers with the wild‐type B‐subunit present in native channels. Overall, cyclic guanosine monophosphate (cGMP) maximum currents of mutant channels were profoundly reduced in homo‐ and heteromers. Treatment with the chemical chaperone glycerol effectively increased macroscopic currents, presumably by enhancing surface expression of mutant channels as confirmed by immunocytochemistry. These results suggest decreased channel density in the cell membrane due to impaired folding or trafficking of the channel protein as the main pathogenic effect of the mutations R427C and R563C. Moreover, A3 R427C homomers showed distinctly increased cGMP and cyclic adenosine monophosphate (cAMP) sensitivities as well as cAMP fractional currents that were raised to over 90% of cGMP maximum currents. Co‐expression of A3 R427C with the B3 subunit compensated for most of these aberrant properties, apart from the reduced cGMP maximum currents.
Discrete Quantum Gravity: I. Zonal spherical functions of the representations of the SO(4,R) group with respect to the SU(2) subgroup and their application to the Barrett-Crane model
2008-04-25

Starting from the defining transformations of complex matrices for the group, we construct the fundamental representation and the tensor and spinor representations of the group . Given the commutation relations for the corresponding algebra, the unitary representations of the group in terms of the generalized Euler angles are constructed. The crucial step for the Barrett-Crane model in Quantum Gravity is the description of the amplitude for the quantum 4-simplex that is used in the state sum partition function. We obtain the zonal spherical functions for the construction of the SO(4,R) invariant weight and associate them to the triangular faces of the 4-simplices.
Red flags for multiple system atrophy
2008-04-28

Abstract The clinical diagnosis of multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA‐P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as “red flags” or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA‐P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA‐SG) was administered to 57 patients with probable MSA‐P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA‐P who on follow‐up fulfilled criteria of probable MSA‐P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA‐P, 76.5% of them would have been correctly diagnosed as probable MSA‐P 15.9 (±7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA‐P. © 2008 Movement Disorder Society.
Multiregional brain iron deficiency in restless legs syndrome
2008-04-28

Abstract Evidence for tissue iron deficiency in restless legs syndrome (RLS) is limited to the substantia nigra (SN). Using MRI, we assessed T2 values of various brain regions in 6 RLS patients and 19 controls and correlated them with sonographically assessed SN echogenicity. Both neuroimaging features are supposed to correlate with tissue iron content. Mean T2 values of all regions were higher in patients (2.9–7.8%), though significantly increased only in four regions; the mean T2 over all voxels was higher in patients (5.1%, P &lt; 0.001) and correlated inversely with SN echogenicity ( r = −0.61, P &lt; 0.001). This indicates multiregional (global) brain iron deficiency in RLS and proposes SN echogenicity as a potential morphological marker for brain iron status. © 2008 Movement Disorder Society
Matrix Metalloproteinases and Their Tissue Inhibitors (TIMPs) inPlasmodium falciparumMalaria: Serum Levels of TIMP‐1 Are Associated with Disease Severity
2008-04-28

TIMP-1 is associated with signs and symptoms of severe malaria. MMP-8 levels are elevated in patients with severe or uncomplicated P. falciparum malaria. MMPs and TIMPs may be relevant in the pathogenesis of severe malaria, either as proteolytic enzymes that degrade the extracellular matrix or as effectors and regulators of the immune response.
The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement
2008-04-29

In this nationwide register, a descriptive classification of patients with disease manifestations characteristic of SSc in five groups allows to include a broader spectrum of patients with features of SSc.
Anemia and splenomegaly in cGKI-deficient mice
2008-04-29

To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in the regulation of erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By the age of 10 weeks, cGKI-deficient mice exhibited pronounced anemia and splenomegaly. Compared with control mice, the cGKI mutants had significantly lower red blood cell count, packed cell volume, and hemoglobin concentration. Anemia was associated with a higher reticulocyte number and an increase of plasma erythropoietin concentration. The spleens of cGKI mutant mice were massively enlarged and contained a higher fraction of Ter119 + erythroid cells, whereas the relative proportion of leukocyte subpopulations was not changed. The Ter119 + cGKI-deficient splenocytes showed a marked increase in annexin V binding, pointing to phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis. Compared with control erythrocytes, cGKI-deficient erythrocytes exhibited in vitro a higher cytosolic Ca 2+ concentration, a known trigger of eryptosis, and showed increased PS exposure, which was paralleled by a faster clearance in vivo . Together, these results identify a role of cGKI as mediator of erythrocyte survival and extend the emerging concept that cGMP/cGKI signaling has an antiapoptotic/prosurvival function in a number of cell types in vivo .
Of Mice, Cattle, and Humans: The Immunology and Treatment of River Blindness
2008-04-29

River blindness is a seriously debilitating disease caused by the filarial parasite Onchocerca volvulus, which infects millions in Africa as well as in South and Central America. Research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. This review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. Experimental findings with Litomosoides sigmodontis in mice and Onchocerca ochengi in cattle are placed in the context of how these models can advance our ability to control the human disease.
Features of TAP‐independent MHC class I ligands revealed by quantitative mass spectrometry
2008-04-29

Abstract TAP is responsible for transferring cytosolic peptides into the ER, where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC class I surface expression and alters the presented peptide pattern. This key molecule in antigen processing is tackled by several viruses and lost in some tumors, rendering the altered cells less vulnerable to T cell‐based immune surveillance. Using the TAP‐deficient cell line LCL721.174 and its TAP‐expressing progenitor cell line LCL721.45, we identified and quantified more than 160 HLA ligands, 50 of which were presented TAP‐independently. Peptides which were predominantly presented on the TAP‐deficient LCL721.174 cell line had a decreased MHC binding affinity according to their SYFPEITHI and BIMAS score. About half of the identified TAP‐independently presented peptides were not derived from signal sequences and may partly be generated by the proteasome. Furthermore, we have excluded the possibility that differences in HLA ligand presentation between LCL721.45 and LCL721.174 were due to varying expression of the source proteins or due to changes in the antigen loading complex. Features of peptides presented independently of TAP as well as proteasomal contribution to their generation provide an insight into basic immunological mechanisms.
Test–Retest Repeatability of Distortion Product Otoacoustic Emissions
2008-04-29

The DPOAE-test-retest study presented here is to our knowledge the first, which combines variation of primary tone levels, assessment of both SF- and MF-modes, and comparison of the two modalities within the same subjects. Although the measurements were conducted under practical conditions resembling the clinical setting, repeatability was generally good. The widely used minimum SNR of 6 dB seems to be a recommendable criterion when considering both practicability and measurement quality under clinical conditions. The current findings underline the suitability of DPOAE as a monitoring tool of cochlear status over time. The data are intended to assist the clinician and the scientist in the correct interpretation of DPOAE level changes in the test-retest situation.