bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aggressive colorectal carcinoma phenotypes of invasion can be assessed reproducibly and effectively predict poor survival: interobserver study and multivariate survival analysis of a prospectively collected series of 299 patients after potentially curative resections with long‐term follow‐up
Authors: Wöhlke Michael , Schiffmann Leif , Prall Friedrich 
Published: November 2011

Wöhlke M, Schiffmann L & Prall F  (2011) Histopathology59, 857–866Aggressive colorectal carcinoma phenotypes of invasion can be assessed reproducibly and effectively predict poor survival: interobserver study and multivariate survival analysis of a prospectively collected series of 299 patients after potentially curative resections with long‐term follow‐upAims:  To test whether assessment of colorectal carcinoma phenotypes of invasion can be taught successfully to pathologists not familiar with these features and to confirm their prognostic impact.Methods and results:  A junior member of staff was supplied with written information and a generous set of images on how to type the invasive margin of colorectal carcinomas (expansive versus infiltrative) and how to assess tumour budding (counting on pan‐cytokeratin immunostains; cut‐off at the 66th percentile). An interobserver study yielded kappa values of 0.578 and 0.438 for typing the invasive margin and assessment of tumour budding, respectively. Margin typing improved significantly to κ = 0.939 after a training session. However, using a cut‐off, assessment of tumour budding improved only moderately to κ = 0.629 although, numerically, divergences were within ±10%. On univariate analysis, a high‐degree of tumour budding and the infiltrative type of invasive margin were strong negative prognostic factors. The Cox model included nodal status, tumour budding, serosal penetration and venous angioinvasion. Importantly, using the tumour budding counts as a numerical variable for the Cox model also yielded significant odds, allowing the constraints of a cut‐off to be relinquished.Conclusions:  Assessment of colorectal carcinoma phenotypes of invasion can be learnt and performed with confidence, and their prognostic impact is confirmed in this independent series.
Human epidermal growth factor receptor 2 (HER2) immunoreactivity: specificity of three pharmacodiagnostic antibodies
Authors: Schrohl Anne‐Sofie , Pedersen Hans Christian , Jensen Sussie Steen , Nielsen Signe Lykke , Brünner Nils 
Published: November 2011

Schrohl A‐S, Pedersen H C, Jensen S S, Nielsen S L & Brünner N  (2011) Histopathology59, 975–983Human epidermal growth factor receptor 2 (HER2) immunoreactivity: specificity of three pharmacodiagnostic antibodiesAims:  The availability of specific antibody‐based test systems is essential to testing of HER2 protein expression. Here, we mapped epitopes recognized by three pharmacodiagnostic HER2 antibodies and investigated their specificity towards peptides and fusion proteins homologous to the intracellular domains of HER1, HER2, HER3 and HER4. The investigated antibodies were PATHWAY® HER2 (clone 4B5; Ventana Medical Systems Inc., Tucson, AZ, USA), HercepTest™ (Dako Denmark A/S, Glostrup, Denmark), and Oracle® HER2 (clone CB11; Leica Microsystems GmbH, Wetzlar, Germany).Methods and results:  Epitopes were mapped using the alanine scanning method. Specificity was investigated in immunohistochemical stainings, competitive enzyme‐linked immunosorbent assay (ELISA) and immunoblotting. All three antibodies reacted with HER2 proteins and peptides in immunohistochemical stainings, ELISA and immunoblotting. PATHWAY® HER2 also stained HER4‐expressing cells, reacted with HER4 peptide in ELISA and detected HER4 fusion protein in an immunoblot. Oracle® HER2 weakly detected HER4 in immunohistochemical stainings, whereas the HercepTest™ antibody showed no cross‐reactivity with other HER proteins.Conclusion:  Our study shows that the PATHWAY® HER2 antibody can bind HER4 peptides and fusion proteins in three different experimental settings. This should be investigated further to determine whether binding of HER4 also occurs in tissue samples and if such binding would have implications for therapy decisions for breast cancer patients.
Dual‐colour chromogenic in‐situ hybridization is a potential alternative to fluorescence in‐situ hybridization in HER2 testing
Authors: Hwang Cheng‐Cheng , Pintye Mariann , Chang Liang‐Che , Chen Huang‐Yang , Yeh Kun‐Yan , Chein Hui‐Ping , Lee Nin , Chen Jim‐Ray 
Published: November 2011

Hwang C‐C, Pintye M, Chang L‐C, Chen H‐Y, Yeh K‐Y, Chein H‐P, Lee N & Chen J‐R  (2011) Histopathology59, 984–992Dual‐colour chromogenic in‐situ hybridization is a potential alternative to fluorescence in‐situ hybridization in HER2 testingAim:  Dual‐colour chromogenic in‐situ hybridization (dc‐CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc‐CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer.Methods and results:  Two hundred and twenty‐eight invasive breast carcinomas arranged in tissue microarrays were analysed in parallel with dc‐CISH, fluorescence in‐situ hybridization (FISH), and immunohistochemistry. Of 227 tumours with available FISH and dc‐CISH results, HER2 amplification and non‐amplification were detected in 49 (21.6%) and 178 (78.4%) tumours, respectively, by both assays. The concordance between dc‐CISH and FISH results showed 100% agreement (κ‐coefficient = 1.00). Immunohistochemically, 162 (71%), 25 (11.0%) and 41 (18%) tumours were scored 0/1+, 2+, and 3+, respectively. The corresponding results with both FISH and dc‐CISH demonstrated HER2 amplification in two (3.2%), nine (36%) and 38 (93%) tumours, respectively. Complete consensus among these three methods was observed in 197 cases, representing 98% of all 3+ and 0/1+ tumours (κ‐coefficient = 0.92). Confirmatory testing of 25 2+ tumours showed complete consensus between FISH and dc‐CISH.Conclusions:  dc‐CISH is a promising alternative to FISH in HER2 testing, and the single‐institute incidence of HER2 amplification in breast cancer in Taiwan is 21.2%.
The savanna‐grassland ‘treeline’: why don’t savanna trees occur in upland grasslands?
Authors: Wakeling Julia L. , Cramer Michael D. , Bond William J. 
Published: November 2011

Summary1. Treeless grasslands with climates that can support tree growth are common in upland regions around the world. In South Africa, the upland grasslands are adjacent to lowland savannas in many areas, with an abrupt boundary between them that could be termed a savanna‐grassland ‘treeline’. Both systems are dominated by C4 grasses and burn regularly, yet fire‐tolerant savanna trees do not survive in the grasslands. The upland grasslands experience lower temperatures throughout the year and frost in winter, compared with the warmer savannas.2. We tested whether frost in the dormant season or slow growth in the growing season in conjunction with frequent fires may explain the tree‐less state of grasslands. We measured Acacia seedling growth for a year in a transplant experiment at ten sites across an altitudinal gradient (42–1704 m) from savannas to grasslands. The effect of frost on seedlings was scored during the following winter.3. Across all species, height (t = −6.04, d.f. = 471, P < 0.001), biomass (t = −4.56, d.f. = 228, P < 0.001) and height increase (t = −3.40, d.f. = 471, P < 0.001) were significantly higher at savanna sites. As the plants were irrigated and initially supplied with nutrients, the main factor affecting growth was likely to be growing season temperature.4. Saplings that experience slow growing conditions will take longer to reach a height above the flame zone and will therefore have a lower probability of reaching adult tree height and surviving fires. Day length may be the most important cue for the end of the growing season in savanna trees, as growth decreased with shortening day length in February–March while temperatures were still high and plants were not water limited.5. Synthesis. Savanna trees grew more slowly in cooler upland grassland sites compared with lower elevation warm savanna sites and, under frequent fire regimes, would be prevented from reaching maturity. This may be true globally for similar grasslands where tree growth can occur and could partly explain the lack of trees in grasslands.
Transmission EBSD from 10 nm domains in a scanning electron microscope
Authors: KELLER R.R. , GEISS R.H. 
Published: November 2011

SummaryThe spatial resolution of electron diffraction within the scanning electron microscope (SEM) has progressed from channelling methods capable of measuring crystallographic characteristics from 10 μm regions to electron backscatter diffraction (EBSD) methods capable of measuring 120 nm particles. Here, we report a new form of low‐energy transmission Kikuchi diffraction, performed in the SEM. Transmission‐EBSD (t‐EBSD) makes use of an EBSD detector and software to capture and analyse the angular intensity variation in large‐angle forward scattering of electrons in transmission, without postspecimen coils. We collected t‐EBSD patterns from Fe–Co nanoparticles of diameter 10 nm and from 40 nm‐thick Ni films with in‐plane grain size 15 nm. The patterns exhibited contrast similar to that seen in EBSD, but are formed in transmission. Monte Carlo scattering simulations showed that in addition to the order of magnitude improvement in spatial resolution from isolated particles, the energy width of the scattered electrons in t‐EBSD is nearly two orders of magnitude narrower than that of conventional EBSD. This new low‐energy transmission diffraction approach builds upon recent progress in achieving unprecedented levels of imaging resolution for materials characterization in the SEM by adding high‐spatial‐resolution analytical capabilities.
Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle
Authors: Juan‐Mateu J , Paradas C , Olivé M , Verdura E , Rivas E , González‐Quereda L , Rodríguez MJ , Baiget M , Gallano P 
Published: November 2011

Juan‐Mateu J, Paradas C, Olivé M, Verdura E, Rivas E, González‐Quereda L, Rodríguez MJ, Baiget M, Gallano P. Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle.X‐linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue. We report a 26‐year‐old male who presented with severe dilated cardiomyopathy and high creatine kinase. The patient did not complain of skeletal muscle weakness. A muscle biopsy showed mild dystrophic changes and a low proportion of dystrophin‐negative fibres. A molecular study identified a nonsense DMD mutation (p.Arg2098X) in somatic mosaicism. The ratio of mutant versus normal allele in blood and skeletal muscle suggests selective pressure against mutant muscle cells, a process known as genetic normalization. We hypothesize that this process may have mitigated skeletal muscle symptoms in this patient. This is the second report of a DMD somatic mosaic with evidence of genetic normalization in muscle. Somatic DMD mutations should be considered in patients presenting with idiopathic dilated cardiomyopathy.
Evaluation of High‐resolution Melting Curve Analysis as a New Tool for Root‐knot Nematode Diagnostics
Authors: Holterman Martijn H. M. , Oggenfuss Markus , Frey Juerg Ernst , Kiewnick Sebastian 
Published: November 2011

AbstractIn the detection of plant pests, speed and accuracy are vital. High‐resolution melting curve (HRMC) analysis was therefore evaluated as a new tool for the identification of root‐knot nematodes (Meloidogyne spp.). On the basis of the second intergenic spacer (IGS2) region of the ribosomal DNA cistron, Meloidogyne chitwoodi, M. fallax and M. hapla were successfully distinguished from each other and the group of the three tropical species, M. incognita, M. arenaria and M. javanica. Conversely, it was shown that the IGS2 region is not suitable for the tropical species M. enterolobii (senior synonym of M. mayaguensis) as the amplification of multiple fragments of different lengths prevented a reliable HRMC analysis. However, the obtained results provide a proof of principle that HRMC analysis can be a suitable single‐tube assay for fast and accurate root‐knot nematode identification.
Impact of insulin pumps on glycaemic control in a pump‐naïve paediatric regional population
Authors: de Bock Martin , Gunn Alistair Jan , Holt Jean‐Ann , Derraik José G B , Reed Peter , Cutfield Wayne , Mouat Fran , Hofman Paul , Jefferies Craig 
Published: November 2011

Aim:  To examine the clinical impact of insulin‐pump therapy for children with type 1 diabetes mellitus (T1DM) in a regional paediatric service, Auckland, New Zealand.Methods:  Retrospective analysis of children with T1DM from the Starship paediatric diabetes database who started on insulin‐pump therapy from 2002 to 2008 compared with the whole T1DM population and with an equal number of non‐pump patients matched by age, sex, ethnicity and duration of diabetes.Results:  From 621 subjects with 6680 clinic visits, 75 children were treated with insulin‐pump therapy for more than 12 months. Transitioning to insulin‐pump treatment was associated with an improvement in HbA1c compared with baseline (−0.3%/year, P < 0.001) for up to 3 years. In contrast, despite similar deprivation scores, non‐pump controls showed a continuing trend to higher HbA1C values (+0.2%/year, P < 0.01). The risk of severe hypoglycaemia fell after pump start (from 27 (0–223) to 5 (0–0.91) events/100 patient years) with no change in non‐pump controls; the rate of diabetic ketoacidosis remained low in both groups.Conclusions:  In a pump‐naïve regional paediatric population, insulin‐pump therapy for T1DM was safe and effective, and associated with sustained improvements in HbA1c and lower risk of hypoglycaemia.
Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium‐dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury
Authors: Gilley Jennifer A. , Kernie Steven G. 
Published: November 2011

AbstractUsing a transgenic mouse (Mus musculus) in which nestin‐expressing progenitors are labeled with enhanced green fluorescent protein, we previously characterized the expression of excitatory amino acid transporter 2 (GltI) and excitatory amino acid transporter 1 (Glast) on early neural progenitors in vivo. To address their functional role in this cell population, we manipulated their expression in P7 neurospheres isolated from the dentate gyrus. We observed that knockdown of GltI or Glast was associated with decreased bromodeoxyuridine incorporation and neurosphere formation. Moreover, we determined that both glutamate transporters regulated progenitor proliferation in a calcium‐dependent and metabotropic glutamate receptor‐dependent manner. To address the relevance of this in vivo, we utilized models of acquired brain injury, which are known to induce hippocampal neurogenesis. We observed that GltI and Glast were specifically upregulated in progenitors following brain injury, and that this increased expression was maintained for many weeks. Additionally, we found that recurrently injured animals with increased expression of glutamate transporters within the progenitor population were resistant to subsequent injury‐induced proliferation. These findings demonstrate that GltI and Glast negatively regulate calcium‐dependent proliferation in vitro and that their upregulation after injury is associated with decreased proliferation after brain trauma.
Age‐related changes in the guinea pig auditory cortex: relationship with brainstem changes and comparison with tone‐induced hearing loss
Authors: Gourévitch Boris , Edeline Jean‐Marc 
Published: November 2011

AbstractElderly people often show degraded hearing performance and have difficulties in understanding speech, particularly in noisy environments. Although loss in peripheral hearing sensitivity is an important factor in explaining these low performances, central alterations also have an impact but their exact contributions remained unclear. In this study, we focus on the functional effects of aging on auditory cortex responses. Neuronal discharges and local field potentials were recorded in the auditory cortex of aged guinea pigs (> 3 years), and several parameters characterizing the processing of auditory information were quantified: the acoustic thresholds, response strength, latency and duration of the response, and breadth of tuning. Several of these parameters were also quantified from auditory brainstem responses collected from the same animals, and recordings obtained from a population of animals with trauma‐induced hearing loss were also included in this study. The results showed that aging and acoustic trauma reduced the response strength at both brainstem and cortical levels, and increased the response latencies more at the cortical level than at the brainstem level. In addition to the brainstem hearing loss, aging induced a ‘cortical hearing loss’ as judged by additive changes in the threshold and frequency response seen in the cortex. It also increased the duration of neural responses and reduced the receptive field bandwidth, effects that were not found in traumatized animals. These effects substantiate the notion that presbycusis involves both peripheral hearing loss and biological aging in the central auditory system.
Semaphorin 3C is not required for the establishment and target specificity of the GABAergic septohippocampal pathway in vitro
Authors: Rubio Sara E. , Martínez Albert , Chauvet Sophie , Mann Fanny , Soriano Eduardo , Pascual Marta 
Published: November 2011

AbstractThe septohippocampal (SH) pathway comprises cholinergic and GABAergic fibers. Whereas the former establish synaptic contacts with all types of hippocampal neurons, the latter form complex baskets specifically on interneurons. The GABAergic SH function is associated with the control of hippocampal synchronous networks. Little is known about the mechanisms involved in the formation of the GABAergic SH pathway. Semaphorin (Sema) 3C is expressed in most hippocampal interneurons targeted by these axons. To ascertain whether Sema 3C influences the formation of the SH pathway, we analyzed the development of this connection in Sema 3C‐deficient mice. As these animals die at birth, we developed an in vitro organotypic co‐culture model reproducing the postnatal development of the SH pathway. In these SH co‐cultures, the GABAergic SH pathway developed with target specificity similar to that present in vivo. SH axons formed incipient baskets on several types of hippocampal interneurons at 7 days in vitro, which increased their complexity by 18–25 days in vitro. These SH fibers formed symmetric synaptic contacts on GABAergic interneurons. This synaptic specificity was not influenced by the absence of entorhinal afferents. Finally, the absence of Sema 3C in target neurons or its blockage by neuropilin‐1 and ‐2 ectodomains in slice co‐cultures did not lead to major changes in either the target specificity of the GABAergic SH pathway or its density of innervation. We conclude that the formation and synaptic specificity of the GABAergic SH pathway relies on robust molecular mechanisms, independent of Sema 3C, that are retained in our in vitro co‐culture model.
HIV‐1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy
Authors: Louboutin Jean‐Pierre , Reyes Beverly A. S. , Agrawal Lokesh , Van Bockstaele Elisabeth J. , Strayer David S. 
Published: November 2011

AbstractMatrix metalloproteinases (MMPs) are implicated in diverse processes, such as neuroinflammation, leakiness of the blood–brain barrier (BBB) and direct cellular damage in neurodegenerative and other CNS diseases. Tissue destruction by MMPs is regulated by their endogenous tissue inhibitors (TIMPs). TIMPs prevent excessive MMP‐related degradation of extracellular matrix components. In a rat model of human immunodeficiency virus (HIV)‐related encephalopathy, we described MMP‐2 and MMP‐9 upregulation by HIV‐1 envelope gp120, probably via gp120‐induced reactive oxygen species. Antioxidant gene delivery blunted gp120‐induced MMP production. We also studied the effect of gp120 on TIMP‐1 and TIMP‐2 production. TIMP‐1 and TIMP‐2 levels increased 6 h after gp120 injection into rat caudate‐putamen (CP). TIMP‐1 and TIMP‐2 colocalized mainly with neurons (92 and 95%, respectively). By 24 h, expression of these protease inhibitors diverged, as TIMP‐1 levels remained high but TIMP‐2 subsided. Gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase or glutathione peroxidase into the CP before injecting gp120 there reduced levels of gp120‐induced TIMP‐1 and TIMP‐2, recapitulating the effect of antioxidant enzymes on gp120‐induced MMP‐2 and MMP‐9. A significant correlation was observed between MMP/TIMP upregulation and BBB leakiness. Thus, HIV‐1 gp120 upregulated TIMP‐1 and TIMP‐2 in the CP. Prior antioxidant enzyme treatment mitigated production of these TIMPs, probably by reducing MMP expression.
Use of a gentamicin‐impregnated collagen sheet (Collatamp®) following implantation of a sacral nerve stimulator for faecal incontinence
Authors: Simpson J. A. D. , Peacock J. , Maxwell‐Armstrong C. 
Published: November 2011

AbstractAim  Gentamicin‐impregnated collagen (Collatamp®) is well described for the prevention of infection in surgery. This technical note describes its intraoperative use as a prophylactic measure to prevent infection following implantation of a sacral nerve stimulator for faecal incontinence.Method  Following implantation of the Interstim II Neurostimulator (Medtronic Neuromodulation, 710 Medtronic Parkway, Minneapolis, USA) in a subcutaneous pocket overlying the gluteal muscle, a single sheet of 10 cm × 10 cm gentamicin‐impregnated collagen is placed within the wound covering the implant. The subcutaneous tissue and skin are then closed in separate layers.Results  To date eight patients [median age 46.5 (30–59) years] have received prophylactic cover with gentamicin‐impregnated collagen following permanent sacral nerve stimulator implantation. At a median interval of 89.5 (51–128) days, none of these patients developed a wound infection at the site of the neurostimulator implant.Conclusion  Gentamicin‐impregnated collagen (Collatamp®) used in the implantation of a sacral nerve stimulator may be a useful addition to the technique.