tbuckley/cabot-search huggingface dataset:
Surgery for Metastatic Urothelial Carcinoma with Curative Intent: The German Experience (AUO AB 30/05)
Authors: Jan Lehmann, Henrik Suttmann, Peter Albers, Björn Volkmer, Jürgen E. Gschwend, Guido Fechner, Martin Spahn, Axel Heidenreich, Axel Odenthal, Christoph Seif, Nils Nürnberg, Christian Wülfing, Christoph Greb, Tilmann Kälble, Marc-Oliver Grimm, Claus Friedrich Fieseler, Susanne Krege, Margitta Retz, Heiner Schulte-Baukloh, Martin Gerber, Markus Hack, Jörn Kamradt, Michael Stöckle
Journal: European Urology (2008)
ECG as a part of the preparticipation screening programme: an old and still present international dilemma
Authors: A Carro Hevia, M M Fernández, J M A Palacio, E H Martín, M G Castro, J J Rodríguez Reguero
Journal: British Journal of Sports Medicine (2009)

Long-term Italian experience has provided evidence that preparticipation screening in competitive athletes with 12-lead ECG, history and physical examination is effective in identifying potentially lethal cardiovascular diseases. However, it is not being routinely practised in other countries.To evaluate the usefulness of a preparticipation screening programme in a sample of players belonging to different disciplines.From September 2006 to June 2008, 1220 young athletes from different sports disciplines underwent a cardiovascular examination that included personal and family history, physical examination and a resting 12-lead ECG. Those with abnormal findings were referred for additional tests.1220 Athletes were screened: 96% males; mean age 23 (4) years. 90 (7.4%) players were referred for additional tests because of abnormal findings on baseline examination: 11 (0.9%) personal or family history, 4 (0.08%) physical examination and 75 (6.14%) 12-lead ECG. Echocardiographic assessment fulfilled left ventricular hypertrophy criteria in 8 of the 90 players. Of those, one case was considered an athlete's heart and one case was diagnosed with hypertrophic cardiomyopathy (septal thickness 23 mm). Further tests were needed in the remaining six, included in the "grey area", with one additional case of hypertrophic cardiomyopathy (apical variant) suggested by cardiac MRI.Given the ability of 12-lead ECG to detect individuals with structural heart disease, we suggest its inclusion as a part of preparticipation screening programmes.
Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography for Interim Response Assessment of Advanced-Stage Hodgkin's Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review
Authors: Teruhiko Terasawa, Joseph Lau, Stéphane Bardet, Olivier Couturier, Tomomitsu Hotta, Martin Hutchings, Takashi Nihashi, Hirokazu Nagai
Journal: Journal of Clinical Oncology (2009)

To systematically review the prognostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for interim response assessment of patients with untreated advanced-stage Hodgkin's lymphoma (HL) or diffuse large B-cell lymphoma (DLBCL).MEDLINE, EMBASE, SCOPUS, and Biologic Abstracts were searched for relevant studies. Two assessors independently reviewed studies for inclusion and extracted data. Relevant unpublished data were requested from the investigators if unavailable from publications. A meta-analysis of the prognostic accuracy was performed.Thirteen studies involving 360 advanced-stage HL patients and 311 DLBCL patients met our inclusion criteria. Advanced-stage HL studies included few unfavorable-risk patients. DLBCL studies were heterogeneous. FDG-PET had an overall sensitivity of 0.81 (95% CI, 0.72 to 0.89) and a specificity of 0.97 (95% CI, 0.94 to 0.99) for advanced-stage HL, and a sensitivity of 0.78 (95% CI, 0.64 to 0.87) and a specificity of 0.87 (95% CI, 0.75 to 0.93) for DLBCL. Meta-regression and subgroup analyses did not identify factors that affect prognostic accuracy.For low- to intermediate-risk advanced-stage HL, FDG-PET performed after a few cycles of standard chemotherapy seems to be a reliable prognostic test to identify poor responders, warranting prospective studies to assess PET-based treatment strategies. For DLBCL, no reliable conclusions can be drawn due to heterogeneity. Interim PET remains an unproven test for routine clinical practice. Its use should be reserved for research settings where treatment regimens and imaging conditions are standardized.
MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis
Authors: Ivy Y Choi, Danielle M Gerlag, Marieke J Herenius, Rogier M Thurlings, Carla A Wijbrandts, Dirk Foell, Thomas Vogl, Johannes Roth, Paul P Tak, Dirk Holzinger
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack of response. The use of predictive biomarkers to identify responders to treatment may provide guidance in optimising treatment strategies and reduce unnecessary side effects and costs. <h3>Objective</h3> To test the ability of myeloid-related proteins (MRP)8/14 protein complexes, an endogenous TLR-4 receptor agonist, to predict and monitor response to biologics in RA patients. <h3>Methods</h3> 170 RA patients treated with adalimumab (n=86), infliximab (n=60) or rituximab (n=24) were categorised into clinical responders (n=123) and non-responders (n=47). MRP8/14 serum complexes were measured at baseline, and 4 and 16 weeks after initiation of treatment and related to response outcome. <h3>Results</h3> Before initiation of treatment, responders showed significantly higher MRP8/14 protein complex levels compared with non-responders in each prospective cohort (p=0.010, p=0.001 and p&lt;0.001, respectively). Logistic regression analysis showed that having high MRP8/14 baseline levels increased the odds of being a responder by 3.3 up to 55. In responders to adalimumab or infliximab treatment, MRP8/14 levels decreased after 4 weeks of treatment by 46% and 60% and after 16 weeks by 61% and 68%, respectively. In contrast, MRP8/14 levels were stable in non-responders. In patients treated with rituximab, MRP8/14 levels decreased by 59% after 16 weeks in responders and increased by 89% after 16 weeks in non-responders. <h3>Conclusion</h3> Serum concentrations of MRP8/14 protein complex are a promising biomarker to predict response to biological therapy in active RA patients at baseline and could be used to monitor response to treatment across different mechanisms of action.
The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport
Authors: Urbain Tchoua, Wilissa D'Souza, Nigora Mukhamedova, Denise Blum, Eric Niesor, Jacques Mizrahi, Cyrille Maugeais, Dmitri Sviridov
Journal: Cardiovascular Research (2007)

AimsCholesteryl ester transfer protein (CETP) has a well-established role in lipoprotein metabolism, but the effect of its overexpression or inhibition on the efficiency of reverse cholesterol transport (RCT) is unclear.
Clostridium difficile Infection in Children
Authors: Julia Shaklee Sammons, Philip Toltzis, Theoklis E Zaoutis
Journal: JAMA Pediatrics (2013)

Clostridium difficile is the most common cause of health care-associated diarrhea among adults in the United States and is associated with significant morbidity and mortality. During the past decade, the epidemiology of C difficile infection (CDI) has changed, including a rise in the rate and severity of infection related to the emergence of a hypervirulent strain as well as an increase in disease among outpatients in community settings. Although less is known about CDI among pediatric patients, C difficile is increasingly recognized as an important pathogen among children. In this review, we discuss recent updates in the incidence and epidemiology of CDI among children, including risk factors for infection, and highlight the importance of CDI in special populations of children, particularly those with inflammatory bowel disease or cancer. In addition, we review current knowledge in the areas of diagnosis and management of CDI among children and highlight future areas for research.
Repression of Prostaglandin Dehydrogenase by Epidermal Growth Factor and Snail Increases Prostaglandin E2 and Promotes Cancer Progression
Authors: Jason R. Mann, Michael G. Backlund, F. Gregory Buchanan, Taki Daikoku, Vijaykumar R. Holla, Daniel W. Rosenberg, Sudhansu K. Dey, Raymond N. DuBois
Journal: Cancer Research (2006)

Abstract Prostaglandin E2 (PGE2), a proinflammatory bioactive lipid, promotes cancer progression by modulating proliferation, apoptosis, and angiogenesis. PGE2 is a downstream product of cyclooxygenase (COX) and is biochemically inactivated by prostaglandin dehydrogenase (PGDH). In the present study, we investigated the mechanisms by which PGDH is down-regulated in cancer. We show that epidermal growth factor (EGF) represses PGDH expression in colorectal cancer cells. EGF receptor (EGFR) signaling induces Snail, which binds conserved E-box elements in the PGDH promoter to repress transcription. Induction of PGE2 catabolism through inhibition of EGFR signaling blocks cancer growth in vivo. In human colon cancers, elevated Snail expression correlates well with down-regulation of PGDH. These data indicate that PGDH may serve a tumor suppressor function in colorectal cancer and provide a possible COX-2–independent way to target PGE2 to inhibit cancer progression. (Cancer Res 2006; 66(13): 6649-56)
Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer
Authors: Antonio C. Wolff, Donald Berry, Lisa A. Carey, Marco Colleoni, Mitchell Dowsett, Matthew Ellis, Judy E. Garber, David Mankoff, Soonmyung Paik, Lajos Pusztai, Mary Lou Smith, JoAnne Zujewski
Journal: Journal of Clinical Oncology (2008)

Preoperative systemic therapy (PST) in operable breast cancer allows a small increase in breast conservation rates and has significant potential as a research platform. PST offers the ability to discern treatment effect in vivo, and may allow smaller trials targeting specific breast cancer subtypes and making more efficient use of resources. Early observations of a specific outcome of interest in individual patient subgroups may improve the design of larger definitive randomized adjuvant trials using survival as a main outcome. PST offers the potential for therapeutic adjustments midcourse, which assumes the existence of validated intermediate end points and effective alternative therapies. This article reviews critical research issues affecting the design of PST trials, including the appropriate selection of trial end points and markers for long-term outcome, baseline marker expression as a predictor of response, and statistical considerations using novel trial designs. Key issues regarding optimal tumor subtype selection for individual trials, novel approaches using nontherapeutic window trial designs, and ethical and advocacy considerations are also discussed. PST requires an experienced and cohesive multidisciplinary team for it to fulfill its potential in both research and clinical care.
FOXC2 Expression Links Epithelial–Mesenchymal Transition and Stem Cell Properties in Breast Cancer
Authors: Brett G. Hollier, Agata A. Tinnirello, Steven J. Werden, Kurt W. Evans, Joseph H. Taube, Tapasree Roy Sarkar, Nathalie Sphyris, Maryam Shariati, Sreedevi V. Kumar, Venkata L. Battula, Jason I. Herschkowitz, Rudy Guerra, Jeffrey T. Chang, Naoyuki Miura, Jeffrey M. Rosen, Sendurai A. Mani
Journal: Cancer Research (2013)

Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial-mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.
Profiling Tumor-Associated Autoantibodies for the Detection of Colon Cancer
Authors: Yuliang Ran, Hai Hu, Zhuan Zhou, Long Yu, Lixin Sun, Jian Pan, Jun Liu, Zhihua Yang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The purpose of the present study was to screen the autoantibody signature of colon cancers to develop serum markers for colon cancer detection. Experimental Design: A phage cDNA expression library of colon cancer was built. The library was sequentially screened by a pool of 10 colon cancer sera, goat antihuman IgG, and a pool of two healthy sera to identify phage-expressed antigens recognized by tumor-associated antibodies. The clones picked out by these screening were subjected to a training set with 24 colon cancer sera and 24 healthy sera. The antigen combination, which got the most satisfactory classification, was tested by an independent set of 24 colon cancer sera with equal number of sera from normal donors. The carcinoembryonic antigen (CEA) level of these sera was detected for the additional classification analysis with or without the antigen combination. Results: A cDNA expression library consisting of 2 × 106 primary clones was prepared. After three turns of screening, 24 antigens recognized by tumor-associated antibodies were picked out for serum marker identification. The training set showed that a six-marker combination got the most satisfactory classification in a logistic regression model; leave-one-out validation achieved 91.7% sensitivity and 91.7% specificity. In a testing set with this marker panel, we correctly predicted 85% of the samples. Although according to CEA level alone, we correctly predicted 75% of the samples with 42% of cancer patients misclassified. When CEA was combined with the six markers, the sensitivity and specificity increased to 91.7% and 95.8%, respectively. The six antigen sequences in the phage display system are relatively short peptides. Only two of them showed homology to known protein sequences. Conclusions: Autoantibodies against phage-expressed antigens derived from colon cancer tissues could be used as serum markers for the detection of colon cancer.
Ticking the right boxes: classification of patients suspected of Lyme borreliosis at an academic referral center in the Netherlands
Authors: J. Coumou, E.A. Herkes, M.C. Brouwer, D. van de Beek, S.W. Tas, G. Casteelen, M. van Vugt, M.V. Starink, H.J.C. de Vries, B. de Wever, L. Spanjaard, J.W.R. Hovius
Journal: Clinical Microbiology and Infection (2014)
Circulating Activated Platelets Reconstitute Lymphocyte Homing and Immunity in L-selectin–Deficient Mice
Authors: Thomas G. Diacovo, Michelle D. Catalina, Mark H. Siegelman, Ulrich H. von Andrian
Journal: The Journal of Experimental Medicine (1998)

Peripheral lymph nodes (PLN) are critical for immunologic memory formation in response to antigens that penetrate the skin. Blood-borne lymphocytes first encounter such antigens after they home to PLN through a multi-step adhesion process that is normally initiated by L-selectin (CD62L) in high endothelial venules (HEV). Since naive T cells can not enter PLN normally in L-selectin–deficient mice, a delayed type hypersensitivity response to cutaneously applied antigen cannot be mounted. In this study, we report that the administration of activated platelets into the systemic circulation of L-selectin knockout mice restores lymphocyte trafficking to PLN, and reconstitutes T cell–mediated immunity in response to a cutaneous antigen. These effects required platelet-expressed P-selectin that allows activated platelets to transiently form a bridge between lymphocytes and HEV, thereby enabling lymphocytes to undergo subsequent β2 integrin-dependent firm adhesion. These profound effects of platelet-mediated cell–cell interactions on lymphocyte trafficking and formation of immunologic memory may impact on a variety of autoimmune and inflammatory conditions.
Factors Contributing to Mammography Failure in Women Aged 40-49 Years
Authors: D. S. M. Buist, P. L. Porter, C. Lehman, S. H. Taplin, E. White
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Younger women (40–49 years) have lower mammographic sensitivity (i.e., greater proportion of cancers detected after a negative mammogram) than older women (≥50 years). We explored the effect of tumor growth rate, breast density, mammographic image quality, and breast cancer risk factors on mammographic sensitivity in younger and older women. Methods: We studied 576 women (n = 73 aged 40–49 years and n = 503 aged 50 years or older) who were diagnosed with invasive breast cancer between 1988 and 1993. Interval cancers were defined as those diagnosed within 12 or 24 months after a negative screening mammogram and before a subsequent mammogram. Tumor growth rate was assessed by mitotic figure count and Ki-67 positivity. The main outcome measures were percentage of women with interval cancer (1 –mammographic sensitivity) by age, odds ratio (OR) of interval cancer by age, and excess odds (i.e., the percentage of the odds ratio for age that was explained by individual covariates). Results: Interval cancers occurred in 27.7% of younger women and 13.9% of older women within 12 months (OR = 2.36, 95% confidence interval [CI] = 1.14 to 4.77) and in 52.1% of younger women and 24.7% of older women within 24 months (OR = 3.58, 95% CI = 2.15 to 5.97). Greater breast density explained 67.6% of the decreased mammographic sensitivity in younger women at 12 months, whereas rapid tumor growth explained 30.6% and breast density explained 37.6% of the decreased sensitivity in younger women at 24 months. Conclusions: Breast density largely explained decreased mammographic sensitivity at 12 months, whereas rapid tumor growth contributed to decreased mammographic sensitivity at 24 months. A 12-month versus a 24-month mammography screening interval may therefore reduce the adverse impact of faster growing tumors on mammographic sensitivity in younger women.
Saliva Polymerase Chain Reaction Assay for Detection and Follow-up of Herpesvirus Reactivation in Patients With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)
Authors: Vincent Descamps, Martine Avenel-Audran, Laurence Valeyrie-Allanore, Benoit Bensaid, Annick Barbaud, Mustafa Al Jawhari, Sylvie Ranger-Rogez
Journal: JAMA Dermatology (2013)

Reactivations of human herpesviruses (HHVs) contribute to the development of drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of HHV reactivation is conventionally based on quantitative real-time polymerase chain reaction (PCR) analysis of blood samples, but these viruses are present in the oropharynx and are shed in saliva.To evaluate the use of a saliva PCR assay for demonstrating HHV shedding in patients with DRESS.Shedding of HHV in saliva was prospectively studied in patients with DRESS. Reactivations of HHV, including HHV-6, HHV-7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), were studied by performing quantitative real-time PCR analysis of blood samples obtained at admission) and serial samples of saliva obtained within the first 2 weeks of DRESS; saliva samples from controls were compared.The study included 5 patients who met definite criteria for DRESS and 15 controls (5 immunosuppressed patients and 10 healthy adults).DNA viral loads of HHV, including HHV-6, HHV-7, CMV, and EBV as measured with real-time PCR in blood and saliva samples from patients with DRESS and saliva samples from immunosuppressed and healthy controls.The PCR assay demonstrated shedding of HHV-7, EBV, HHV-6, and CMV, listed by order of magnitude. The DNA viral loads in blood and saliva samples, also measured with real-time PCR, were found to be close. In 1 patient, reactivations in saliva preceded clinical manifestations of CMV disease. Significant production of HHV-7 and EBV was demonstrated in saliva samples from the controls, but neither HHV-6 nor CMV were detected.The saliva PCR assay is a useful tool for demonstration and follow-up of HHV reactivation. The interpretation of HHV viral loads in saliva differs according to HHV type.
Impact of Early Surgery on Embolic Events in Patients With Infective Endocarditis
Authors: Dae-Hee Kim, Duk-Hyun Kang, Myung-Zoon Lee, Sung-Cheol Yun, Yong-Jin Kim, Jong-Min Song, Jae-Kwan Song, Jae-Won Lee, Dae-Won Sohn
Journal: Circulation (2010)

Background— Surgical indications to prevent systemic embolism in infective endocarditis (IE) remain controversial. We sought to compare clinical outcomes of early surgery with conventional treatment in IE patients with embolic indications only. Methods and Results— From 1998 to 2006, we prospectively enrolled 132 consecutive patients (86 men; age, 49±17 years) with definite IE. Patients were included if they had a left-sided native valve endocarditis with vegetation. The choice of early surgery or conventional treatment was at the discretion of attending physician. Early surgery was performed on 64 patients (OP group) within 7 days of diagnosis, and conventional management was chosen for 68 patients (CONV group). The OP group had larger vegetations and a higher percentage of patients with severe valvular disease (88% versus 62%, P =0.001). During initial hospitalization, there were no embolic events and 2 in-hospital deaths in the OP group and 14 embolic events and 2 in-hospital deaths in the CONV group. During a median follow-up of 1402 days, there were 2 cardiovascular deaths, 2 embolic events, and 1 recurrence of IE in the CONV group, and 1 cardiovascular death and 2 embolic events in the OP group. The 5-year event-free survival rate was significantly higher in the OP group (93±3%) than in the CONV group (73±5%, P =0.0016). For 44 propensity score–matched pairs, the OP group had a lower event rate (hazard ratio, 0.18; P =0.007). Conclusions— Compared with conventional treatment, an early surgery strategy is associated with improved clinical outcomes by effectively decreasing systemic embolism in patients with IE.