bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perception of global gestalt by temporal integration in simultanagnosia
Authors: Huberle Elisabeth , Rupek Paul , Lappe Markus , Karnath Hans‐Otto 
Published: December 2008

AbstractPatients with bilateral parieto‐occipital brain damage may show intact processing of individual objects, while their perception of multiple objects is disturbed at the same time. The deficit is termed ‘simultanagnosia’ and has been discussed in the context of restricted visual working memory and impaired visuo‐spatial attention. Recent observations indicated that the recognition of global shapes can be modulated by the spatial distance between individual objects in patients with simultanagnosia and thus is not an all‐or‐nothing phenomenon depending on spatial continuity. However, grouping mechanisms not only require the spatial integration of visual information, but also involve integration processes over time. The present study investigated motion‐defined integration mechanisms in two patients with simultanagnosia. We applied hierarchical organized stimuli of global objects that consisted of coherently moving dots (‘shape‐from‐motion’). In addition, we tested the patients’ ability to recognize biological motion by presenting characteristic human movements (‘point‐light‐walker’). The data revealed largely preserved perception of biological motion, while the perception of motion‐defined shapes was impaired. Our findings suggest separate mechanisms underlying the recognition of biological motion and shapes defined by coherently moving dots. They thus argue against a restriction in the overall capacity of visual working memory over time as a general explanation for the impaired global shape recognition in patients with simultanagnosia.
Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons
Authors: Cooper Deborah S. , Yang Han Soo , He Peijian , Kim Eunjin , Rajbhandari Ira , Yun Chris C. , Choi Inyeong 
Published: December 2008

AbstractGrowing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO3transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pHo) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pHo7.4. At pHo6.5, the intracellular pH of neurons was ∼1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pHo6.5. NBCn1 expression also increased by 40% in a prolonged Mg2+‐free incubation at normal pHo. Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mmglutamate for 10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pHo7.2 for 6 h) after glutamate exposure, acidic incubation (pHo 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1‐knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg2+‐free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pHoand Mg2+depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg2+‐free conditions.
Size of sampling unit strongly influences detection of seedling limitation in a wet tropical forest
Authors: Kobe Richard K. , Vriesendorp Corine F. 
Published: December 2008

AbstractSeedling limitation could structure communities, but often is evaluated with sampling units that are orders of magnitude smaller than mature plants. We censused seedlings for 5.5 years in five 1 × 200‐m transects in a wet Neotropical forest. For 106 common species (≥ 10 seedlings in a transect), we calculated prevalence (occurrence of ≥ 1 newly emerged seedlings per sampling unit) at 1 m2 and at 1 m × mature crown diameter units by aggregating adjacent quadrats. For most species, prevalence was 2–25% at 1 m2, but 20–92% at mature crown scales. Increased prevalence arose from broadly distributed seedlings within transects, with unoccupied segments generally shorter than crown diameters. At the landscape scale, 69% of 301 species were locally rare (< 10 seedlings) and only 16% were represented in all transects (maximally separated by 2.4 km). Nonetheless, for more common species, much lower estimates of seedling limitation at mature crown scales suggest weaker influence of seedling limitation on community dynamics than previously assumed.
Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population‐based study
Authors: Kvåle Rune , Møller Bjørn , Wahlqvist Rolf , Fosså Sophie D. , Berner Aasmund , Busch Christer , Kyrdalen Anne E. , Svindland Aud , Viset Trond , Halvorsen Ole J. 
Published: December 2008

OBJECTIVETo study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population‐based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen.PATIENTS AND METHODSThrough the Cancer Registry of Norway, we identified 1116 patients with available Gleason scores from biopsy and RP specimens. Concordance was evaluated using the κ coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses.RESULTSThe Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy‐based Gleason score more often under‐graded (38%) than over‐graded (9%) the RP‐based Gleason score. Pathology units that examined >40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lower‐volume units. The rate of upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen increased with increasing preoperative prostate‐specific antigen serum levels, and with increasing intervals between biopsy and RP.CONCLUSIONSThe concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.
Bacille‐Calmette Guèrin induces caspase‐independent cell death in urothelial carcinoma cells together with release of the necrosis‐associated chemokine high molecular group box protein 1
Authors: See William A. , Zhang Guangjian , Chen Fanghong , Cao Yanli , Langenstroer Peter , Sandlow Jay 
Published: December 2008

OBJECTIVETo evaluate the ability of bacille‐Calmette Guèrin (BCG) to induce caspase‐independent cell death and release the necrosis‐associated chemokine high molecular group box protein 1 (HMGB1) from urothelial carcinoma (UC) cells; a correlative clinical trial determined if BCG treatment resulted in increased urinary levels of HMGB1.PATIENTS, MATERIALS AND METHODSThe human UC cell lines 253 J and T24 were pretreated with apoptosis inhibitors, exposed to BCG, and cell viability and ultrastructural changes measured. HMGB1 levels were assessed in cell culture supernatant after BCG treatment. The expression/function of HMGB1 receptors on the UC cell lines was determined by reverse transcription‐polymerse chain reaction and the ability of exogenous HMGB1 to activate nuclear factor (NF)‐κB signalling assessed. An HMGB1 enzyme‐linked immunosorbent assay was used to measure HMGB1 levels in urine obtained from BCG‐treated patients.RESULTSInhibition of apoptotic pathways failed to inhibit BCG‐induced cell death in UC cells. Electron microscopy showed BCG‐dependent ultrastructural changes consistent with cellular necrosis. BCG exposure resulted in a binary increase in cell culture supernatant levels of HMGB1. UCs expressed multiple HMGB1 receptors. Treatment of UCs with HMGB1 activated NF‐κB. In the clinical setting, six of seven patients had increased urinary levels of HMGB1 at 24 h after BCG treatment.CONCLUSIONSBCG causes direct cytotoxicity in a subpopulation of UC cells. This cytotoxicity is caspase‐independent and associated with ultrastructural changes and cellular protein release (HMGB1), characteristic of necrosis. Urinary levels of HMGB1 can be elevated in patients after BCG treatment. The expression and function of HMGB1 receptors in UC cells, coupled with the known role of HMGB1 on the host immune response, suggest a role for necrosis and HMGB1 release in the antitumour effect of BCG.
Concomitant repeated intravesical injections of botulinum toxin‐type A and laparoscopic antegrade continence enema; a new solution for an old problem
Authors: Kajbafzadeh AbdolMohammad , Mahboubi Amir Hassan , Payabvash Seyedmehdi 
Published: December 2008

OBJECTIVETo report our experience of treating bladder and bowel dysfunction in children with myelomeningocele, with simultaneous laparoscopic antegrade continence enema (LACE) and repeated intravesical injection of botulinum toxin‐type A (BTX‐A).PATIENTS AND METHODSSix girls and 14 boys (mean age, 8.7 years) with myelomeningocele were included in this study. All patients had received one or two intravesical injection(s) of BTX‐A, but had persistent fecal incontinence or constipation despite improved urinary symptoms. We performed a two‐port laparoscopic appendicostomy, immediately after repeated intravesical injection of BTX‐A, through a V‐shaped skin flap at McBurney’s point. The stoma was finally covered by a quadrilateral skin flap, using the ‘VQ’ technique. The degree of urinary incontinence and bowel dysfunction were determined in each patient, and conventional urodynamic studies were performed 4 months after each injection.RESULTSAll patients were followed‐up for a mean (range) of 19.1 (14–33) months. Urinary continence improved significantly after the first injection, and remained constant after repeat injections. The maximum detrusor pressure, bladder compliance and capacity improved significantly (P < 0.001) compared with baseline. Interestingly, the simultaneous intravesical BTX‐A injection/LACE procedure significantly improved all urodynamic variables compared with the values obtained after the last BTX‐A injection alone. The laparoscopic procedure was well tolerated, and 19 (95%) children were nappy‐free at the final follow‐up. Only two patients had stoma stenosis, and one patient had minor stoma leakage.CONCLUSIONConcomitant repeat intravesical injection of BTX‐A and LACE can effectively manage bladder and bowel dysfunction in children with myelomeningocele. The procedure may further contribute to improve bladder urodynamic function, as effective evacuation of the bowel provides more room for bladder distension.
Urokinase‐plasminogen‐activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer
Authors: Thomas Christian , Wiesner Christoph , Melchior Sebastian W. , Schmidt Folke , Gillitzer Rolf , Thüroff Joachim W. , Pfitzenmaier Jesco 
Published: December 2008

OBJECTIVETo evaluate the expression of urokinase‐plasminogen‐activator receptor (uPA‐R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis.PATIENTS AND METHODSIn all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA‐R expression was detected by dual‐immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow‐up was initiated to detect tumour relapse (defined as a prostate‐specific antigen (PSA) level of ≥0.2 ng/mL).RESULTSOverall, there was expression of ‘CK + uPA‐R’ in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high‐risk cancer (P = 0.005). The relative risk for CK + uPA‐R expression in the BM was 3.1 times higher in high‐risk than in low‐risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA‐R expression in BM or PB. The PSA‐recurrence free survival was significantly lower in patients with CK + uPA‐R‐positive BM cells (P = 0.01).CONCLUSIONIn this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high‐risk disease. All patients with a later PSA relapse had had uPA‐R expression in their DTC from the BM. DTC with uPA‐R expression was an adverse prognostic factor for prostate cancer.
Safety and efficacy of inhaled insulin (AERx® iDMS1) compared with subcutaneous insulin therapy in patients with Type 1 diabetes: 1‐year data from a randomized, parallel group trial
Authors: Moses R. G. , Bartley P. , Lunt H. , O’Brien R. C. , Donnelly T. , Gall M.‐A. , Vesterager A. , Wollmer P. , Roberts A. 
Published: December 2008

AbstractAims  Assessment of the long‐term safety and efficacy of liquid inhaled insulin via AERx® insulin Diabetes Management System (iDMS) in a basal/bolus treatment regimen of adults with Type 1 diabetes.Methods  Patients were randomized 2 : 1 to prandial inhaled (n = 205) or subcutaneous (s.c.) (n = 99) insulin, plus one/two daily injections of neutral protamine Hagedorn (NPH) insulin for 12 months. The primary endpoints were pulmonary function tests (PFT) and baseline changes in chest X‐rays at 12 months. Safety and efficacy assessments were measured at regular intervals.Results  PFTs after 12 months were comparable between the groups, except for reduced per cent of predicted carbon monoxide lung diffusing capacity with inhaled insulin (difference: –2.03%, P = 0.04) occurring after the first 3 months and then stabilizing. There were no apparent treatment differences in chest X‐rays. Overall risk of hypoglycaemia [risk ratio (RR) 1.02, P = 0.83] and adverse events were comparable between groups. Risk of nocturnal hypoglycaemia was higher in the inhaled group (RR 1.58, P = 0.001). Cough [10% (inhaled); 3% (s.c.)] tended to be mild in nature. Inhaled insulin was non‐inferior to s.c. insulin for change in glycated haemoglobin (HbA1c) after 12 months [difference 0.18% (CI 95%–0.04; 0.39)]. At trial end, mean laboratory measured fasting plasma glucose was lower in the inhaled group (inhaled 9.2 mmol/l; s.c. 11.7 mmol/l; difference: –2.53 mmol/l, P < 0.001).Conclusions  The safety and efficacy results in this trial were similar to those reported with other inhaled insulins; however, inhaled insulin using AERx® iDMS requires further optimization to reduce nocturnal hypoglycaemia before it has comparable safety and efficacy to s.c. insulin aspart.
The effect of a cognitive or motor task on gait parameters of diabetic patients, with and without neuropathy
Authors: Paul L. , Ellis B. M. , Leese G. P. , McFadyen A. K. , McMurray B. 
Published: December 2008

AbstractAims  To compare gait parameters of older people with diabetes and no peripheral neuropathy (DM) and people with diabetes and diabetic peripheral neuropathy (DPN) and to investigate the effect of a secondary motor or cognitive task on their gait.Methods  Thirty subjects were recruited: 15 with DPN (mean age 69 ± 3.0 years) and 15 with diabetes and no neuropathy (70 ± 2.9 years). The temporal and spatial parameters of gait were determined using the GAITRite walkway. Subjects undertook four walks: under normal walking conditions (single task); four times while simultaneously undertaking an additional motor task, carrying a tray with cups of water (dual task); and four times whilst undertaking a cognitive dual task, counting backwards in sevens. This arithmetic task was also completed sitting.Results  For all gait variables, there was a statistically significant difference between the groups. Subjects with DPN walked more slowly and with smaller steps compared with those with DM. In general, the secondary task had a significant and adverse effect on the gait parameters and this effect was greater for those with DPN in both absolute and relative terms. Both groups had poorer arithmetic ability when walking compared with sitting.Discussion  Patients with DPN have different gait parameters to diabetic patients without neuropathy. Problems with divided attention when walking were more evident in the DPN group and may increase their risk of falls.
A global study of relationships between leaf traits, climate and soil measures of nutrient fertility
Authors: Ordoñez Jenny C. , Van Bodegom Peter M. , Witte Jan‐Philip M. , Wright Ian J. , Reich Peter B. , Aerts Rien 
Published: December 2008

ABSTRACTAim  This first global quantification of the relationship between leaf traits and soil nutrient fertility reflects the trade‐off between growth and nutrient conservation. The power of soils versus climate in predicting leaf trait values is assessed in bivariate and multivariate analyses and is compared with the distribution of growth forms (as a discrete classification of vegetation) across gradients of soil fertility and climate.Location  All continents except for Antarctica.Methods  Data on specific leaf area (SLA), leaf N concentration (LNC), leaf P concentration (LPC) and leaf N:P were collected for 474 species distributed across 99 sites (809 records), together with abiotic information from each study site. Individual and combined effects of soils and climate on leaf traits were quantified using maximum likelihood methods. Differences in occurrence of growth form across soil fertility and climate were determined by one‐way ANOVA.Results  There was a consistent increase in SLA, LNC and LPC with increasing soil fertility. SLA was related to proxies of N supply, LNC to both soil total N and P and LPC was only related to proxies of P supply. Soil nutrient measures explained more variance in leaf traits among sites than climate in bivariate analysis. Multivariate analysis showed that climate interacted with soil nutrients for SLA and area‐based LNC. Mass‐based LNC and LPC were determined mostly by soil fertility, but soil P was highly correlated to precipitation. Relationships of leaf traits to soil nutrients were stronger than those of growth form versus soil nutrients. In contrast, climate determined distribution of growth form more strongly than it did leaf traits.Main conclusions  We provide the first global quantification of the trade‐off between traits associated with growth and resource conservation ‘strategies’ in relation to soil fertility. Precipitation but not temperature affected this trade‐off. Continuous leaf traits might be better predictors of plant responses to nutrient supply than growth form, but growth forms reflect important aspects of plant species distribution with climate.
Some Asymptotic Results on Generalized Penalized Spline Smoothing
Authors: Kauermann Göran , Krivobokova Tatyana , Fahrmeir Ludwig 
Published: December 2008

SummaryThe paper discusses asymptotic properties of penalized spline smoothing if the spline basis increases with the sample size. The proof is provided in a generalized smoothing model allowing for non-normal responses. The results are extended in two ways. First, assuming the spline coefficients to be a priori normally distributed links the smoothing framework to generalized linear mixed models. We consider the asymptotic rates such that the Laplace approximation is justified and the resulting fits in the mixed model correspond to penalized spline estimates. Secondly, we make use of a fully Bayesian viewpoint by imposing an a priori distribution on all parameters and coefficients. We argue that with the postulated rates at which the spline basis dimension increases with the sample size the posterior distribution of the spline coefficients is approximately normal. The validity of this result is investigated in finite samples by comparing Markov chain Monte Carlo results with their asymptotic approximation in a simulation study.
CSF biomarker profile and diagnostic value in vascular dementia
Authors: Paraskevas G. P. , Kapaki E. , Papageorgiou S. G. , Kalfakis N. , Andreadou E. , Zalonis I. , Vassilopoulos D. 
Published: December 2008

Background and purpose:  The differential diagnosis between vascular dementia (VD) and Alzheimer’s disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (τT) or hyperphosphorylated at threonin‐181(τP‐181) form and beta amyloid peptide 1–42 (Aβ42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD.Methods:  The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme‐linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls.Results:  Alzheimer’s disease and MD showed increased levels of τT, τP and reduced levels of Aβ42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying ≥85% of patients, either in the form of a discriminant function or in the form of the τT × τP‐181/Aβ42 formula.Conclusions:  Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.
Successful treatment of refractory generalized myasthenia gravis with rituximab
Authors: Lebrun C. , Bourg V. , Tieulie N. , Thomas P. 
Published: December 2008

Objective:  Myasthenia gravis (MG) is an autoimmune neuromuscular disorder for which current therapies carry a high risk of side‐effects and may be insufficient in stabilizing the clinical status. Many therapeutic options can be ruled, such as thymectomy, corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, intravenous immunoglobulin (IVIg) or less frequently plasmapheresis must be ruled.Methods:  We followed prospectively six patients with MG who presented with a poor response to two or three lines of immunosuppressive conventional drugs associated with oral corticosteroids. All but one were acetylcholine receptor negative and three were anti‐MuSK positive. IVIg did not improved the neurological status and all patient required high doses of cholinesterase inhibitors.Results:  Rituximab was introduced with a mean follow‐up of 1.5 years (375 mg/m2, days 1, 8, 15, 28 during the first month and then one dose every 2 months). After 2 years of follow‐up, all patients stopped corticosteroids and tapered off cholinesterase inhibitors from 60 to 180 mg/day without severe infectious events.Conclusion:  Rituximab, a chimeric IgG k monoclonal antibody that target CD20 is used for the treatment of relapsing/refractory CD20 positive low‐grade non‐Hodgkin’s lymphoma and other autoimmune neuromuscular diseases. Four previous short reports have described a good response of MG associated with lymphoma with rituximab. It appears to be a promising and effective drug for the treatment of MG without lymphoma, with a substantial benefit to the clinical status and good tolerability.