bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLIC4, ERp29, and Smac/DIABLO Derived from Metastatic Cancer Stem–like Cells Stratify Prognostic Risks of Colorectal Cancer
Authors: Deng Yong-Jian , Tang Na , Liu Chao , Zhang Jiang-Yu , An Sheng-Li , Peng Yin-Li , Ma Li-Li , Li Guang-Qiu , Jiang Qiang , Hu Chun-Ting , Wang Ya-Nan , Liang Yao-Ze , Bian Xiu-Wu , Fang Wei-Gang , Ding Yan-Qing 
Published: June 2014

Abstract
Purpose: Cancer stem–like cells have been well accepted to be involved in recurrence and metastasis of cancers, but the prognostic potential of biomarkers integrating with metastasis and cancer stem–like cells for colorectal cancer is unclear.
Experimental Design: We identified three proteins, CLIC4, ERp29, and Smac/DIABLO, from metastatic cancer stem–like cells of colorectal cancer and verified the proteins' role in metastatic behaviors. The proteins were detected by IHC in colorectal cancer tumors and matched colonic mucosa from patients with colorectal cancer who underwent radical surgery in the training cohort. The associations between proteins expression levels and five-year disease-specific survival (DSS) were evaluated to predict the survival probability in the training cohort of 421 cases and the validation cohort of 228 cases.
Results: A three-protein panel including CLIC4, ERp29, and Smac/DIABLO, which was generated from multivariate analysis by excluding clinicopathologic characteristics from the training cohort, distinguished patients with colorectal cancer into very low-, low-, middle-, and high-risk groups with significant differences in five-year DSS probability (88.6%, 63.3%, 30.4%, 11.4%; P &lt; 0.001). The panel is independent from tumor–node–metastasis staging system and histologic grading to predict prognosis, and also enables classification of validation cohort into four risk stratifications (five-year DSS probability is 98.2%, 80.2%, 25.6%, and 2.7%; P &lt; 0.001).
Conclusions: CLIC4, ERp29, and Smac/DIABLO integrated into a novel panel based on cancer stem–like cells in association with metastasis stratify the prognostic risks of colorectal cancer. Prediction of risks with molecular markers will benefit clinicians to make decisions of individual management with postoperative colorectal cancer patients. Clin Cancer Res; 20(14); 3809–17. ©2014 AACR.
Kidney Cancer Is Characterized by Aberrant Methylation of Tissue-Specific Enhancers That Are Prognostic for Overall Survival
Authors: Hu Caroline Y. , Mohtat Davoud , Yu Yiting , Ko Yi-An , Shenoy Niraj , Bhattacharya Sanchari , Izquierdo Maria C. , Park Ae Seo Deok , Giricz Orsolya , Vallumsetla Nishanth , Gundabolu Krishna , Ware Kristin , Bhagat Tushar D. , Suzuki Masako , Pullman James , Liu X. Shirley , Greally John M. , Susztak Katalin , Verma Amit 
Published: June 2014

Abstract
Purpose: Even though recent studies have shown that genetic changes at enhancers can influence carcinogenesis, most methylomic studies have focused on changes at promoters. We used renal cell carcinoma (RCC), an incurable malignancy associated with mutations in epigenetic regulators, as a model to study genome-wide patterns of DNA methylation at a high resolution.
Experimental Design: Analysis of cytosine methylation status of 1.3 million CpGs was determined by the HELP assay in RCC and healthy microdissected renal tubular controls.
Results: We observed that the RCC samples were characterized by widespread hypermethylation that preferentially affected gene bodies. Aberrant methylation was particularly enriched in kidney-specific enhancer regions associated with H3K4Me1 marks. Various important underexpressed genes, such as SMAD6, were associated with aberrantly methylated, intronic enhancers, and these changes were validated in an independent cohort. MOTIF analysis of aberrantly hypermethylated regions revealed enrichment for binding sites of AP2a, AHR, HAIRY, ARNT, and HIF1 transcription factors, reflecting contributions of dysregulated hypoxia signaling pathways in RCC. The functional importance of this aberrant hypermethylation was demonstrated by selective sensitivity of RCC cells to low levels of decitabine. Most importantly, methylation of enhancers was predictive of adverse prognosis in 405 cases of RCC in multivariate analysis. In addition, parallel copy-number analysis from MspI representations demonstrated novel copy-number variations that were validated in an independent cohort of patients.
Conclusions: Our study is the first high-resolution methylome analysis of RCC, demonstrates that many kidney-specific enhancers are targeted by aberrant hypermethylation, and reveals the prognostic importance of these epigenetic changes in an independent cohort. Clin Cancer Res; 20(16); 4349–60. ©2014 AACR.
Conflit entre narration et création dans La maison des temps rompus de Pascale Quiviger
Authors: Ali Suzette 
Published: June 2014

Dans notre article, nous étudions les entorses faites à la narration homodiégétique dans le roman La maison des temps rompus de Pascale Quiviger. Ces entorses illustrent les divergences analytiques qui existent dans les observations théoriques du concept de narrateur, et convoquent le conflit existentiel généré par les romanciers classiques entre la figure du narrateur et la figure de l’écrivain.
Quand l’auteur joue à disparaître: figurations auctoriales et mystifications à l’époque romantique (Les Veillées du Tasse et Les Soirées de Walter Scott à Paris)”
Authors: Feuillebois Victoire 
Published: June 2014

L’article se propose d’illustrer un paradigme théorique récent, celui des « figurations auctoriales », qui a contribué à renouveler l’étude de l’auteur et de l’auctorialité dans les études françaises. Ce paradigme permet de revenir sur le discrédit jeté par le structuralisme et la théorie de la déconstruction sur les manifestations de l’auteur dans le texteet les représentations directes de sa voix: il s’agit pour nous de relire cette présence à la lumière de l’histoire culturelle et de montrer que ces figurations auctoriales n’ont vocation ni à représenter fidèlement l’auteur réel, ni à mimer les instances narratives effectives du texte. C’est ce que montre de manière exemplaire la mystification romantique, où l’auteur joue à disparaître derrière une figure trompeuse, pour mieuxaffirmer son pouvoir narratif. Elleconstitue une stratégie hybride: lesécrivains attirent leurs lecteurs parla promesse d’un contact direct avecl’auteur, mais élaborent une mani-pulation narrative qui renvoie le lec-teur au seul texte.
Leukocyte Invasion of the Brain After Experimental Intracerebral Hemorrhage in Mice
Authors: Mracsko Eva , Javidi Ehsan , Na Shin-Young , Kahn Alexandra , Liesz Arthur , Veltkamp Roland 
Published: June 2014

Background and Purpose—
Neuroinflammatory processes contribute to secondary neuronal damage after intracerebral hemorrhage. We aimed to characterize the time course of brain immigration of different leukocyte subsets after striatal injection of either autologous blood or collagenase in mice.

Methods—
Intracerebral hemorrhage was induced by injection of either autologous blood (20 μL) or collagenase (0.03 U) in C57Bl/6J mice. Hematoma volumetry was performed on cryosections. Blood volume was measured by hemoglobin spectrophotometry. Leukocytes were isolated from hemorrhagic hemisphere 1, 3, 5, and 14 days after intracerebral hemorrhage, stained for leukocyte markers, and measured by flow cytometry. Heterologous blood injection from CD45.1 mice was used to investigate the origin of brain-invading leukocytes.

Results—

Collagenase injection induced a larger hematoma volume but a similar blood content compared with blood injection. Cerebral leukocyte infiltration in the hemorrhagic hemisphere was similar in both models. The majority of leukocytes isolated from the brain originated from the circulation. CD4
+
T lymphocytes were the predominant brain leukocyte population in both models. However, cerebral granulocyte counts were higher after collagenase compared with blood injection.

Conclusions—
Brain infiltration of systemic immune cells is similar in both murine intracerebral hemorrhage models. The pathophysiological impact of invading leukocytes and, in particular, of T cells requires further investigation.
<span lang="EN-US">Epipactis krymmontana</span><span lang="EN-US"> (Orchidaceae), a new species endemic to the Crimean Mountains and notes on the related taxa in the Crimea and bordering Russian Caucasus</span>
Authors: Fateryga Alexander V. , Kreutz Karel C.A.J. , Fateryga Valentina V. , Efimov Petr G. 
Published: June 2014

A new obligately self-pollinating species, Epipactis krymmontana, is described from the Crimea. The species is closely related to E. condensata from which it differs by its relatively loose and usually much shorter inflorescence, relatively elongate ovaries, much paler epichile with less protruding bosses and absence of a viscidium. It grows in beech forests, often mixed with oak and hornbeam, on calcareous soils. The new species was previously misidentified in the Crimea as E. purpurata or sometimes as E. condensata, the latter growing in hot, sunny places with sparse vegetation. The presence of typical E. condensata in the Crimea is considered doubtful, but it is undoubtedly present in the Russian Caucasus along with E. condensata subsp. kuenkeleana, which is a new combination proposed in place of E. purpurata subsp. kuenkeleana. Epipactis purpurata should be excluded both from the floras of the Crimea and the Russian Caucasus. An updated key to the species of Epipactis sect. Epipactis in the Crimea and Russian Caucasus is provided.
Gross Moist Stability and MJO Simulation Skill in Three Full-Physics GCMs
Authors: Benedict James J. , Maloney Eric D. , Sobel Adam H. , Frierson Dargan M. W. 
Published: June 2014

Abstract
Previous studies have demonstrated a link between gross moist stability (GMS) and intraseasonal variability in theoretical and reduced-complexity models. In such simplified models, MJO-like moisture modes—convectively coupled tropical disturbances akin to the MJO whose formation and dynamics are linked to moisture perturbations—develop only when GMS is either negative or “effectively” negative when considering additional sources of moist entropy. These simplified models typically use a prescribed, time-independent GMS value. Limited work has been done to assess GMS and its connection to intraseasonal variability in full-physics general circulation models (GCMs).
The time-mean and intraseasonal behavior of normalized GMS (NGMS) are examined in three pairs of GCMs to elucidate the possible importance of NGMS for the MJO. In each GCM pair, one member produces weak intraseasonal variability, while the other produces robust MJOs because of a change in the treatment of deep convection. A strong linear correlation between time-mean NGMS and MJO simulation skill is observed, such that GCMs with less positive NGMS produce improved MJO eastward propagation. The reduction in time-mean NGMS is primarily due to a sharp drop to negative values in the NGMS component related to vertical advection, while the horizontal advection component has a less clear relationship with MJO simulations. Intraseasonal fluctuations of anomalous NGMS modulate the magnitude of background NGMS but generally do not change the sign of background NGMS. NGMS declines ahead of peak MJO rainfall and increases during and after heaviest precipitation. Total NGMS fluctuates during MJO passage but remains positive, suggesting that other sources of moist entropy are required to generate an effectively negative NGMS.
Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor
Authors: Wang Xunde , Mendelsohn Laurel , Rogers Heather , Leitman Susan , Raghavachari Nalini , Yang Yanqin , Yau Yu Ying , Tallack Michael , Perkins Andrew , Taylor James G. , Noguchi Constance Tom , Kato Gregory J. 
Published: June 2014

Key Points
Heme-bound iron activates placenta growth factor expression in erythroid cells via EKLF, a crucial erythroid-specific transcription factor. Markers of iron burden predict mortality in adults with sickle cell disease.
Construction and evaluation of a novel humanized HER2-specific chimeric receptor
Authors: Sun Meili , Shi Huan , Liu Chuanyong , Liu Jie , Liu Xianqiang , Sun Yuping 
Published: June 2014

Abstract
Introduction
The human epidermal growth factor receptor 2 (HER2) represents one of the most studied tumor-associated antigens (TAAs) for cancer immunotherapy. The monoclonal antibody (mAb) trastuzumab has improved the outcomes of patients with HER2+ breast cancer. However, a large number of HER2+ tumors are not responsive to, or become resistant to, trastuzumab-based therapy, and thus more effective therapies targeting HER2 are needed.

Methods
HER2-specific T cells were generated by the transfer of genes that encode chimeric antigen receptor (CAR). Using a multistep overlap extension PCR method, we constructed a novel, humanized HER2 CAR-containing, chA21 single-chain variable fragment (scFv) region of antigen-specific mAb and T-cell intracellular signaling chains made up of CD28 and CD3ζ. An interferon γ and interleukin 2 enzyme-linked immunosorbent assay and a chromium-51 release assay were used to evaluate the antitumor immune response of CAR T cells in coculture with tumor cells. Furthermore, SKBR3 tumor–bearing nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were treated with HER2 CAR T cells to evaluate antitumor activity. Human CD3+ T cell accumulation in tumor xenograft was detected by immunohistochemistry.

Results
chA21-28z CAR was successfully constructed, and both CD4+ and CD8+ T cells were transduced. The expanded HER2 CAR T cells expressed a central memory phenotype and specifically reacted against HER2+ tumor cell lines. Furthermore, the SKBR3 tumor xenograft model revealed that HER2 CAR T cells significantly inhibited tumor growth in vivo. Immunohistochemical analysis showed robust accumulation of human CD3+ T cells in regressing SKBR3 lesions.

Conclusions
The results of this study show that novel chA21 scFv-based, HER2-specific CAR T cells not only recognized and killed HER2+ breast and ovarian cancer cells ex vivo but also induced regression of experimental breast cancer in vivo. Our data support further exploration of the HER2 CAR T-cell therapy for HER2-expressing cancers.
Nicastrin and Notch4 drive endocrine therapy resistance and epithelial to mesenchymal transition in MCF7 breast cancer cells
Authors: Lombardo Ylenia , Faronato Monica , Filipovic Aleksandra , Vircillo Valentina , Magnani Luca , Coombes R Charles 
Published: June 2014

Abstract
Introduction
Resistance to anti-estrogen therapies is a major cause of disease relapse and mortality in estrogen receptor alpha (ERα)-positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependence of breast cancer cells on Notch signalling. Here, we investigated the contribution of Nicastrin and Notch signalling in endocrine-resistant breast cancer cells.

Methods
We used two models of endocrine therapies resistant (ETR) breast cancer: tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF7 cells. We evaluated the migratory and invasive capacity of these cells by Transwell assays. Expression of epithelial to mesenchymal transition (EMT) regulators as well as Notch receptors and targets were evaluated by real-time PCR and western blot analysis. Moreover, we tested in vitro anti-Nicastrin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. Finally, we generated stable Nicastrin overexpessing MCF7 cells and evaluated their EMT features and response to tamoxifen.

Results
We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and displayed increased levels of Nicastrin and Notch targets. Interestingly, we detected higher level of Notch4 but lower levels of Notch1 and Notch2 suggesting a switch to signalling through different Notch receptors after acquisition of resistance. Anti-Nicastrin monoclonal antibodies and the GSI PF03084014 were effective in blocking the Nicastrin/Notch4 axis and partially inhibiting the EMT process. As a result of this, cell migration and invasion were attenuated and the stem cell-like population was significantly reduced. Genetic silencing of Nicastrin and Notch4 led to equivalent effects. Finally, stable overexpression of Nicastrin was sufficient to make MCF7 unresponsive to tamoxifen by Notch4 activation.

Conclusions
ETR cells express high levels of Nicastrin and Notch4, whose activation ultimately drives invasive behaviour. Anti-Nicastrin mAbs and GSI PF03084014 attenuate expression of EMT molecules reducing cellular invasiveness. Nicastrin overexpression per se induces tamoxifen resistance linked to acquisition of EMT phenotype. Our finding suggest that targeting Nicastrin and/or Notch4 warrants further clinical evaluation as valid therapeutic strategies in endocrine-resistant breast cancer.
Ultrasound of the groin region following surgical intervention of the great saphenous vein
Authors: Mendoza E. 
Published: June 2014

ZusammenfassungEin wichtiger Bestandteil der phlebologischen chirurgischen Therapie ist die Kontrolle nach der Operation – die auch im Wesentli-chen der Qualitätskontrolle dienen sollte. Hierbei spielt die Sonographie die Hauptrolle, um insbesondere auch frühe Rezidive darzustellen (1). Die Rezidive nach chirurgischem Eingriff am saphenofemoralen Übergang bilden das größte Problem nach Varizenbehandlung. Verschiedene Versuche, diese zu stratifizieren sind noch nicht zu einem hinreichend übersichtlichen Ergebnis gekommen (1, 5–7). Der vorliegende Beitrag möchte die duplexsonographische Untersuchung der Region des sapheno-femoralen Übergangs nach Krossektomie und nach endoluminal thermischen Verfahren beleuchten. Der Normalbefund und die verschiedenen Rezidivmöglichkeiten werden beschrieben.
Compression treatment in venous insufficiency and arterial disease
Authors: Mosti G. 
Published: June 2014

SummaryCompression therapy is one of cornerstone in the treatment of venous and lymphatic disorders.It may be applied by means of different elastic or inelastic stockings, bandages, or other devices. Inelastic material is much more effective improving venous impaired haemodynamics than elastic material. Due to its physical properties inelastic material is able to exert a significantly higher pressure than elastic devices moving to the standing from the supine pressure; furthermore it is able to exert significantly higher pressure peaks during muscle exercise. This high pressure can overcome the intravenous pressure and cause intermittent occlusion of leg veins, restoring a kind of valve mechanism. Elastic material gives way to the muscle expansion during standing and walking and the pressure increase in these conditions is very low. Due to this low increase with muscle activity, elastic material does not exert an intermittent pressure but rather a sustained pressure not able to overcome the intravenous pressure. As a consequence, elastic material is hardly able to influence the venous diameter and its haemodynamic effects are minimal.Compared to elastic, inelastic material is significantly more effective in reducing venous reflux, increasing venous pumping function and reducing ambulatory venous hypertension.Compression therapy proved to be beneficial, over time, in every clinical condition from CEAP C1 to C6.Due to their characteristics and effects, in-elastic compression needs to be applied in the acute stages of venous disorders when a strong haemodynamic effect is necessary, while elastic stockings may be used in the chronic stages to maintain the results and prevent recurrences.A new concept in compression therapy is the inversely graduated compression pressure profile, higher over the calf than over the ankle, also named “progressive compression.” Both specially designed elastic stockings and appropriately applied bandages can exert a progressive compression which showed some interesting outcomes both in experimental and clinical settings in patients with chronic venous disorders and in athletes. Nevertheless its effectiveness in many pathological conditions (oedema treatment, venous leg ulcer, thromboprophylaxis, etc.) needs to be proved in future trials.
Perennial allergic rhinitis
Authors: Cross Sue 
Published: June 2014

The nose is the first part of the natural airway, a fact often forgotten by doctors and nurses alike. Airflow in the nose is rapid, and during a sniff it ean easily reach the speed of a hurricane! It draws in all the airborne pollutants and particles and filters most of them out of the inhaled air before they reach the sensitive lining of the lungs. The mucosa of the nose are, however, as prone to irritation and allergy as any other part of the skin, and where an allergen is constantly present inflammation of the mucous membranes, rhinitis, can be a permanent condition (Mygind et al, 1996). Perennial allergic rhinitis, where a substance that is not harmful causes an immune response, can be separated from non-allergic rhinitis, where the offending substance cannot be identified. Sue Cross discusses the management of this unpleasant complaint.
Injectable progestogens
Authors: Szarewski Anne 
Published: June 2014

Injectable contraceptives are still a minority use method of contraception in this country. In women under the age of thirty the most commonly used method is the combined oral contraceptive pill. In 1995, three and a quarter million women were using the pill. Sterilisation of one or other partner is also common in this country, especially in couples where the woman is over thirty. Injectable progestogens may be the right choice of contraceptive for some patients, as Anne Szarewski explains.
Oral anticoagulation in the community
Authors: Baird Anne 
Published: June 2014

The primary and secondary prevention of stroke, ischaemic heart disease and other thromboembolic disorders is now an accepted part of the role of many practice nurses. Various drugs are used in these disorders to inhibit the clotting process (Lancaster et al, 1997) and an understanding of their mode of action is vital to nurses working in this area. In the first of three articles Anne Baird outlines the fundamentals of the clotting process.
The unstable bladder and urinary incontinence
Authors: Kelham Ian 
Published: June 2014

Bladder problems of one sort or another are very common and are estimated to affect up to 6 million people in the UK. Of these, between 2 and 3 million suffer from urinary incontinence (Thomas et al, 1980). However, it is thought that less than a third of those with moderate or severe urinary incontinence seek medical help (Largo-Janssen et al, 1990), because of embarrassment, denial or the mistaken, but widespread, belief that their problem cannot be effectively treated.
Causes and assessment of faecal incontinence
Authors: Chelanayagam Sonya , Norton Christine 
Published: June 2014

Faecal incontinence is defined as the involuntary or inappropriate passing of liquid or solid stool (Royal College of Physicians, 1995). Anal incontinence is the term used to define any involuntary leakage from the anus, whether of solid, liquid or flatus. Faecal incontinence remains a taboo subject as Sonya Chelvanayagam and Christine Norton explain.
HIV treatment: where are we now?
Authors: Staveley Sarah 
Published: June 2014

The widespread use of highly active anti-retroviral therapy (HAART) since the summer of 1996 has brought many changes to the outlook and care of HIV positive clients and service provision. The routine use of increasingly intensive anti-retroviral therapies has resulted directly in dramatic declines in morbidity and mortality among HIV-infected patients with advanced immune depletion (Palella et al, 1998).