bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic significance of APC gene mutation and miR‐21 expression in advanced‐stage colorectal cancer
Authors: Chen T.‐H. , Chang S.‐W. , Huang C.‐C. , Wang K.‐L. , Yeh K.‐T. , Liu C.‐N. , Lee H. , Lin C.‐C. , Cheng Y.‐W. 
Published: June 2013

AbstractAimColorectal cancer (CRC) is the second commonest cause of cancer death in Taiwan. Although numerous genes have been associated with tumorigenesis in colorectal cancer, only a few have been validated and used as biomarkers for predicting clinical outcome. The aim of this study was to analyse the association of APC gene mutation and miR‐21 expression with clinical outcome in CRC patients.MethodIn total, 195 colorectal cancer patients were enrolled in a single medical centre between 2003 and 2007. APC gene mutation and expression of APC and miR‐21 were analysed by direct DNA sequencing and real‐time reverse transcription polymerase chain reaction. The primary outcome included 5‐year overall survival and univariate (Kaplan–Meier) and multivariate (Cox regression) analyses of prognostic factors.ResultsThe results showed that 66 (33.8%) of 195 tumour tissues contained an APC mutation. The predominant APC gene variations were deletion mutations (50.0%). APC gene expression was low in CRC and negatively correlated with miR‐21 expression and gene mutation. In advanced‐stage cancer, patients with APC mutation/high miR‐21 had poorer overall survival rates than those with APC mutation/low miR‐21, APC wild‐type/high miR‐21 and APC wild‐type/low miR‐21.ConclusionIn Taiwan, downregulation of the APC gene in CRC correlated with gene mutation and miR‐21 upregulation. APC mutation and miR‐21 expression could be used to predict the clinical outcome of CRC, especially in patients with advanced disease.
Comparison of three‐dimensional high‐resolution manometry and endoanal ultrasound in the diagnosis of anal sphincter defects
Authors: Vitton V. , Ben Hadj Amor W. , Baumstarck K. , Behr M. , Bouvier M. , Grimaud J.‐C. 
Published: June 2013

AbstractAimThree‐dimensional high‐resolution anorectal manometry (3D HRAM) is a new technique that can simultaneously provide physiological and topographical data. Our aim was to assess whether it can identify anal sphincter defects by comparing it with endoanal ultrasonography (EUS) considered as the gold standard.MethodAn anal defect on 3D HRAM was defined as a continuous circumferential area over which the pressure was < 10 mmHg during the measurement of anal resting and voluntary contraction pressure. Inter‐observer agreement was also assessed.ResultsA total of 100 patients (93 females) with a mean age of 53.5 ± 15.3 years were included. The positive diagnosis of an anal sphincter defect using 3D HRAM and EUS was in agreement (59.3%) (κ = 0.419) of the time for the internal anal sphincter (IAS) and (55.9%) (κ = 0.461) for the external anal sphincter (EAS). The inter‐observer agreement for a diagnosis of an anal sphincter defect was (100%) (κ = 0.937) for the IAS and (95%) (κ = 0.751) for the EAS. The intra‐class correlation coefficient for the extent of the defect was 0.853 for the IAS and 0.651 for the EAS.ConclusionThe preliminary results demonstrate some level of agreement in the diagnosis of anal sphincter defects between 3D HRAM and EUS but insufficient for 3D HRAM to be adequately reliable using the criteria chosen. The excellent inter‐observer agreement, however, demonstrates that 3D HRAM is reproducible and provides a new dimension for the evaluation of sphincter function.
Phospho‐mTOR is not upregulated in metastatic SDHB paragangliomas
Authors: Ghayee Hans K. , Giubellino Alessio , Click Arielle , Kapur Payal , Christie Alana , Xie Xian‐Jin , Martucci Victoria , Shay Jerry W. , Souza Rhonda F. , Pacak Karel 
Published: June 2013

AbstractBackgroundPheochromocytomas (PCCs)/paragangliomas (PGLs) are neuroendocrine tumours that may cause arrhythmia and death if untreated. Treatment for patients with metastatic tumours is lacking. As new PCC/PGL susceptibility genes are discovered that are associated with the mTOR pathway, treatment targets focusing on this pathway are being intensively explored.DesignTwenty‐one human PCC/PGLs were analysed from two tertiary care centres. Immunohistochemistry (IHC) analysis was performed for phospho‐mTOR (pmTOR), phospho‐S6K (pS6K), phosphoinositide 3‐kinase (PI3K), phospho‐4EBP1 (p4EBP1), HIF1α and MIB‐1 in 6 metastatic SDHB PCC/PGLs, 15 nonmetastatic PCC/PGLs, (including 1 TMEM127 PCC and 1 nonmetastatic SDHB PGL) and 6 normal adrenal medullas. The product of the intensity of stain and percentage of cells stained was calculated as an H score.ResultsUsing a two‐sample t‐test and paired t‐test, pmTOR and pS6K had significantly higher H scores in nonmetastatic PCC/PGLs than in metastatic SDHB PCC/PGLs. HIF1α had significantly higher H scores in metastatic SDHB PCC/PGLs compared with nonmetastatic PCC/PGLs and normal adrenal medulla. No difference in H scores was seen with p4EBP1, PI3K and MIB‐1 when comparing metastatic SDHB PCC/PGLs and nonmetastatic PCC/PGLs. Significantly higher difference in pS6K was seen in normal adrenal medullas compared to nonmetastatic PCC/PGLs and metastatic SDHB PCC/PGLs.ConclusionThe present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC/PGLs may not achieve good therapeutic efficacy in patients.
Variation in duration of untreated psychosis in an 18‐year perspective
Authors: ten Velden Hegelstad Wenche , Joa Inge , Barder Helene , Evensen Julie , Haahr Ulrik , Johannessen Jan O. , Langeveld Johannes , Melle Ingrid , Opjordsmoen Stein , Røssberg Jan Ivar , Rund Bjørn Rishovd , Simonsen Erik , Vaglum Per , McGlashan Thomas , Friis Svein , Larsen Tor K. 
Published: June 2013

AbstractAimThe Scandinavian TIPS project engineered an early detection of psychosis programme that sought to reduce the duration of untreated psychosis (DUP) through early detection teams and extensive information campaigns since 1997. In 1997–2000, DUP was reduced from 26 to 4.5 weeks median. The programme was continued beyond the initial project in modified forms for over 13 years. The aim of this study was to track the vicissitudes of DUP over an 18‐year period (1993–2010) with differing early detection efforts in a defined catchment area.MethodThe DUP of all patients meeting criteria for first episode psychosis was measured 1993–1994 and from 1997 to 2010 in a naturalistic long‐term study. DUP values of all patients were included, irrespective of patients' participation in a clinical follow‐up study, yielding a highly representative sample.ResultsDUP varied across studies with differing information campaign intensity and content. These variations will be described and explored.ConclusionsEarly detection campaigns should have a stable focus and high intensity level. Future research should further elucidate pathways to care in order to establish principal targets for information campaigns.
Prospective study of the course of delusional themes in first‐episode non‐affective psychosis
Authors: Ellersgaard Ditte , Mors Ole , Thorup Anne , Jørgensen Per , Jeppesen Pia , Nordentoft Merete 
Published: June 2013

AbstractAimThe stability of delusional themes in psychotic disorders is only sparsely lit. The study aims to investigate the stability of delusional themes over a period of time in patients with first‐episode non‐affective psychosis.MethodsThe data were drawn from a randomized controlled trial of 547 first‐episode patients with schizophrenia spectrum disorders, the OPUS trial. A subsample of 411 patients met our inclusion criteria. They were interviewed at the time of first treatment contact, and at years 1, 2 and 5 after onset. The delusional themes of the 411 patients were classified by applying principal component analysis to the patients' scores on 12 items of delusions from the Scale for the Assessment of Positive Symptoms in Schizophrenia, SAPS. The course of the patients' predominant delusional themes was analysed afterwards.ResultsThe 12 delusional themes from SAPS were converted into five groups using principal component analysis. At all three follow ups there were almost equal proportions of patients with the predominant delusion being from the same group of delusional themes as at baseline and of patients with the predominant delusion being from another group of delusional themes than at baseline.ConclusionsThe predominant delusional theme at the time of first treatment contact was seen to be only of some predictive value to the predominant delusional theme at the later follow‐up points in patients with first‐episode non‐affective psychosis. This stresses the importance of a systematic assessment of different delusional themes in the continued monitoring of early signs of psychotic relapse and at each psychotic episode.
Attitudes of patients and clinicians in relation to the at‐risk state for psychosis
Authors: Welsh Patrick , Tiffin Paul A. 
Published: June 2013

AbstractAimIn the last decade, advances have been made in identifying young people who may be at relatively high risk (HR) of developing psychosis. Given the controversial and experimental nature of the HR concept, the attitudes and experiences of mental health professionals and patients are likely to influence practice in this area. Previous work has been published that has speculated on the potential risks and advantages of identifying and intervening within the HR state. However, few have attempted to capture the attitudes and experiences of patients and professionals towards this concept. This article provides, via the collation of existing research reports, a reflection on the views, attitudes and experiences of these key stakeholders.MethodsA narrative review of the literature was undertaken focussing upon the following key areas: mental health professionals’ attitudes towards the HR concept, patients’ attitudes towards the HR concept, attitudes of patients towards potential treatments and attitudes of professionals towards HR treatments.ResultsRelatively few published studies focusing on the attitudes and experiences of patients and mental health professionals exist. However, there is some evidence that both professionals and affected individuals view the HR concept as worthy of diagnosis and intervention. Expressed treatment preferences appear to vary, dependent on the group of individuals surveyed.ConclusionsFurther systematic studies of patient and professional preferences, in relation to identification and intervention, are desirable in order to explore the way that the HR denotation is personally interpreted and the extent to which it affects patient and practitioner behaviour.
Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification
Authors: Wolfe Devin M. , Lee Ju‐hyun , Kumar Asok , Lee Sooyeon , Orenstein Samantha J. , Nixon Ralph A. 
Published: June 2013

AbstractAutophagy is a lysosomal degradative process which recycles cellular waste and eliminates potentially toxic damaged organelles and protein aggregates. The important cytoprotective functions of autophagy are demonstrated by the diverse pathogenic consequences that may stem from autophagy dysregulation in a growing number of neurodegenerative disorders. In many of the diseases associated with autophagy anomalies, it is the final stage of autophagy–lysosomal degradation that is disrupted. In several disorders, including Alzheimer's disease (AD), defective lysosomal acidification contributes to this proteolytic failure. The complex regulation of lysosomal pH makes this process vulnerable to disruption by many factors, and reliable lysosomal pH measurements have become increasingly important in investigations of disease mechanisms. Although various reagents for pH quantification have been developed over several decades, they are not all equally well suited for measuring the pH of lysosomes. Here, we evaluate the most commonly used pH probes for sensitivity and localisation, and identify LysoSensor yellow/blue‐dextran, among currently used probes, as having the optimal profile of properties for measuring lysosomal pH. In addition, we review evidence that lysosomal acidification is defective in AD and extend our original findings, of elevated lysosomal pH in presenilin 1 (PS1)‐deficient blastocysts and neurons, to additional cell models of PS1 and PS1/2 deficiency, to fibroblasts from AD patients with PS1 mutations, and to neurons in the PS/APP mouse model of AD.
Aging and neurogenesis in the adult forebrain: what we have learned and where we should go from here
Authors: Hamilton Laura K. , Joppé Sandra E. , M. Cochard Loїc , Fernandes Karl J. L. 
Published: June 2013

AbstractIn the brains of adult vertebrates, including humans, neurogenesis occurs in restricted niches where it maintains cellular turnover and cognitive plasticity. In virtually all species, however, aging is associated with a significant decline in adult neurogenesis. Moreover, an acceleration of neurogenic defects is observed in models of Alzheimer's disease and other neurodegenerative diseases, suggesting an involvement in aging‐ and disease‐associated cognitive deficits. To gain insights into when, how and why adult neurogenesis decreases in the aging brain, we critically reviewed the scientific literature on aging of the rodent subventricular zone, the neurogenic niche of the adult forebrain. Our analysis revealed that deficits in the neurogenic pathway are largely established by middle age, but that there remains striking ambiguity in the underlying mechanisms, especially at the level of stem and progenitor cells. We identify and discuss several challenging issues that have contributed to these key gaps in our current knowledge. In the future, addressing these issues should help untangle the interactions between neurogenesis, aging and aging‐associated diseases.
Alterations in hippocampal network oscillations and theta–gamma coupling arise before Aβ overproduction in a mouse model of Alzheimer's disease
Authors: Goutagny Romain , Gu Ning , Cavanagh Chelsea , Jackson Jesse , Chabot Jean‐Guy , Quirion Rémi , Krantic Slavica , Williams Sylvain 
Published: June 2013

AbstractAlzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by memory impairments. Brain oscillatory activity is critical for cognitive function and is altered in AD patients. Recent evidence suggests that accumulation of soluble amyloid‐beta (Aβ) induces reorganization of hippocampal networks. However, whether fine changes in network activity might be present at very early stages, before Aβ overproduction, remains to be determined. We therefore assessed whether theta and gamma oscillations and their cross‐frequency coupling, which are known to be essential for normal memory function, were precociously altered in the hippocampus. Electrophysiological field potential recordings were performed using complete hippocampal preparations in vitro from young transgenic CRND8 mice, a transgenic mouse model of AD. Our results indicate that a significant proportion of 1‐month‐old TgCRND8 mice showed robust alterations of theta–gamma cross‐frequency coupling in the principal output region of the hippocampus, the subiculum. In addition we showed that, compared to controls, these mice expressed negligible levels of Aβ. Finally, these network alterations were not due to genetic factors as 15‐day‐old animals did not exhibit theta–gamma coupling alterations. Thus, initial alterations in hippocampal network activity arise before Aβ accumulation and may represent an early biomarker for AD.
Calorie restriction alleviates the age‐related decrease in neural progenitor cell division in the aging brain
Authors: Park June‐Hee , Glass Zachary , Sayed Kasim , Michurina Tatyana V. , Lazutkin Alexander , Mineyeva Olga , Velmeshev Dmitry , Ward Walter F. , Richardson Arlan , Enikolopov Grigori 
Published: June 2013

AbstractProduction of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age‐related cognitive deficits. Restriction of calorie intake and prolonged treatment with rapamycin have been shown to extend the lifespan of animals and delay the onset of the age‐related decline in tissue and organ function. Using a reporter line in which neural stem and progenitor cells are marked by the expression of green fluorescent protein (GFP), we examined the effect of prolonged exposure to calorie restriction (CR) or rapamycin on hippocampal neural stem and progenitor cell proliferation in aging mice. We showed that CR increased the number of dividing cells in the dentate gyrus of female mice. The majority of these cells corresponded to nestin–GFP‐expressing neural stem or progenitor cells; however, this increased proliferative activity of stem and progenitor cells did not result in a significant increase in the number of doublecortin‐positive newborn neurons. Our results suggest that restricted calorie intake may increase the number of divisions that neural stem and progenitor cells undergo in the aging brain of females.
A dual‐porous, inverse model of water retention to study biological and hydrological interactions in soil
Authors: Laudone G. M. , Matthews G. P. , Gregory A. S. , Bird N. R. A. , Whalley W. R. 
Published: June 2013

SummaryThe deterministic modelling of bio‐hydrological processes in soil requires a void structure model that is explicitly dual‐porous containing fully and separately characterized macroporosity and microporosity. It should also contain information that relates the positioning of microporosity relative to macroporosity. An example of such a process is the production of nitrous oxide, in which bacteria in microporous ‘hot‐spots’ are supplied with nutrients and gases through a macroporous pathway. We present a precision void‐structure model that satisfies these two criteria, namely explicit macroporosity and microporosity, and their positional relationship. To demonstrate the construction of the model, we describe the modelling of a single soil, namely Warren soil from Rothamsted Research's Woburn Experimental Farm in Bedfordshire, UK, although the modelling approach is applicable to a wide range of soils and other dual porous solids. The model is capable of fitting several fundamental properties of soil, namely water retention, aggregate size distribution, and porosity of the microporous and macroporous zones. It comprises a dendritic critical percolation path, around which are clustered the microporous regions. The saturated hydraulic conductivity of the dual‐porous network is of the correct order of magnitude for a soil of the same density and texture as the Warren sample. Finally, we demonstrate how the preferential flow pathway in the resulting structure differs from the critical percolation pathway, and that only 4.6% by volume of the unclogged macroporosity contributes to the fluid flow through the structure.
Phosphatidylinositol 3‐kinases inhibitor LY294002 potentiates the cytotoxic effects of doxorubicin, vincristine, and etoposide in a panel of cancer cell lines
Authors: Badinloo Marzieh , Esmaeili‐Mahani Saeed 
Published: June 2013

AbstractMany novel therapeutic approaches to overcome chemoresistance have involved targeting specific signaling pathways such as the phosphatidylinositol 3‐kinase (PI3K) pathway. PI3K is a known stress response pathway which is involved in the regulation of cell survival, apoptosis, and growth. Inhibition of this pathway may possibly restore or augment the effectiveness of chemotherapy. Using three human malignant cell lines, we examined the effects of LY294002 (PI3K inhibitor) on chemotherapeutic agent‐induced apoptosis and cytotoxicity. An antimicrotubule agent vincristine, a topoisomerase II inhibitor etoposide, and a DNA cross‐linking agent doxorubicin were used accompanied with LY294002. Cell viability was determined by MTT assay, and the induction of apoptosis was assessed by immunoblotting of caspase‐3. Blocking the PI3K/Akt cascade with a PI3K inhibitor LY294002 (10 μM) increased the cytotoxic effect of vincristine and doxorubicin on SK‐OV‐3 cell line. Furthermore, LY294002 showed a greater promoting effect in etoposide‐ and doxorubicin‐induced cytotoxicity on MDA‐MB‐468 and A549 cells. The quantity of cleaved caspase‐3 in cancer cells that had combination therapy was increased compared with that in the cells treated with each drug alone. We suggest that inhibitors of the PI3K/Akt pathway in combination with chemotherapeutic agents may induce cell death effectively and be a potent modality to treat various types of cancer. The effectiveness of such combination therapy is depending to the used cell line and class of anticancer drug.
Increased temperature reduces herbivore host‐plant quality
Authors: Bauerfeind Stephanie S. , Fischer Klaus 
Published: June 2013

AbstractGlobally increasing temperatures may strongly affect insect herbivore performance, as their growth and development is directly linked to ambient temperature as well as host‐plant quality. In contrast to direct effects of temperature on herbivores, indirect effects mediated via thermal effects on host‐plant quality are only poorly understood, despite having the potential to substantially impact performance and thereby to alter responses to the changing climatic conditions. We here use a full‐factorial design to explore the direct (larvae were reared at 17 °C or 25 °C) and indirect effects (host plants were reared at 17 °C or 25 °C) of temperature on larval growth and life‐history traits in the temperate‐zone butterfly Pieris napi. Direct temperature effects reflected the common pattern of prolonged development and increased body mass at lower temperatures. At the higher temperature, efficiency of converting food into body matter was much reduced being accompanied by an increased food intake, suggesting compensatory feeding. Indirect temperature effects were apparent as reduced body mass, longer development time, an increased food intake, and a reduced efficiency of converting food into body matter in larvae feeding on plants grown at the higher temperature, thus indicating poor host‐plant quality. The effects of host‐plant quality were more pronounced at the higher temperature, at which compensatory feeding was much less efficient. Our results highlight that temperature‐mediated changes in host‐plant quality are a significant, but largely overlooked source of variation in herbivore performance. Such effects may exaggerate negative effects of global warming, which should be considered when trying to forecast species' responses to climate change.
‘DAS ES TEUTSCHE ZUNG VERNIMPT’: ZUR ÜBERSETZUNGSLITERATUR TIROLS UM 1400
Authors: Harris Nigel 
Published: June 2013

ABSTRACTThe achievement of Vienna (and particularly of its University) in spreading the culture of late‐medieval Latinity via translations into German is well known. Much less thoroughly explored, however, is the role played by contemporary Tyrolean translators in building a bridge between their German audiences and a variety of important products of medieval Latin, French, and Italian literature. This article foregrounds three South Tyrolean translations, by Michel Velser, Hans Vintler, and Ulrich Putsch, and refers also to the anonymous Tiroler Petrarca‐Übersetzung. All of these were composed between roughly 1390 and 1430, and transmit versions of texts that had enjoyed enormous popularity in the Romance lands. The piece focuses especially on questions of translation technique and of reception. It concludes that there is no firm evidence on which to postulate the existence of a concerted Tyrolean ‘school’ of translators or the involvement of a particular influential patron, but demonstrates that the cultural ‘bridge’ built by these Tyrolean authors was a significant and multi‐faceted one, which as such merits far more investigation. It also provides further evidence to support medievalists’ increasing awareness that medieval books were often in practice owned and read by rather different people from those whom their authors had envisaged.