tbuckley/cabot-search huggingface dataset:
Tumor Hypoxia Regulates Forkhead Box C1 to Promote Lung Cancer Progression
Authors: Yu-Jung Lin, Woei-Cherng Shyu, Chi-Wei Chang, Chi-Chung Wang, Chung-Pu Wu, Hsu-Tung Lee, Liang-Jwu Chen, Chia-Hung Hsieh
Journal: Theranostics (2017)

Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription factors that are characterized by a DNA-binding forkhead domain.Increasing evidence indicates that FOXC1 is involved in tumor progression.However, the role of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression are unclear.Here, we report that FOXC1 was upregulated in hypoxic areas of lung cancer tissues from rodents or humans.Hypoxic stresses significantly induced FOXC1 expression.Moreover, hypoxia activated FOXC1 transcription via direct binding of hypoxia-inducible factor-1α (HIF-1α) to the hypoxia-responsive element (HRE) in the FOXC1 promoter.FOXC1 gain-of-function in lung cancer cells promoted cell proliferation, migration, invasion, angiogenesis, and epithelial-mesenchymal transition in vitro.However, a knockdown of FOXC1 in lung cancer cells inhibited these effects.Notably, knockdown of tumor hypoxia-induced FOXC1 expression via HIF-1-mediated FOXC1 shRNAs in lung cancer xenograft models suppressed tumor growth and angiogenesis.Finally, systemic delivery of FOXC1 siRNA encapsulated in lipid nanoparticles inhibited tumor growth and increased survival time in lung cancer-bearing mice.Taken together, these data indicate that FOXC1 is a novel hypoxia-induced transcription factor and plays a critical role in tumor microenvironment-promoted lung cancer progression.Systemic FOXC1 blockade therapy may be an effective therapeutic strategy for lung cancer.
Observatoire national de l'endoscopie par capsule colique: résultats finalisés de suivi et de comparaison capsule-coloscopie des 283 premiers patients
Authors: JC Saurin, R Benamouzig, T Ponchon, JP Galmiche, S Sacher-Huvelin, E Samaha
Journal: Endoscopy (2017)

L'ONECC est un observatoire national de la capsule colique ayant permis la réalisation de 1400 examens entre 2011 et 2014, et permettant l'évaluation en pratique courante, hors étude institutionnelle, de cet examen nouveau. Nous présentons les résultats finalisés de l'ensemble du suivi des patients et de la concordance capsule-coloscopie des premiers dossiers intégralement analysés.
Comparative proteomic analysis of radiation induced changes in non small cell lung cancer patients with or without radiation induced lung toxicity
Authors: X. Cai, K. Shedden, X. Ao, T. S. Lawrence, D. M. Lubman, F. Kong
Journal: Journal of Clinical Oncology (2009)

e22146 Background: Radiation-induced lung toxicity (RILT) is dose limiting in the treatment of non small cell lung cancer (NSCLC). Early prediction of RILT would allow physicians to individualize treatment. This work aims to study if radiation induces differential changes in plasma proteomics in patients with and without RILT. Methods: 20 Patients with NSCLC in 3 stage- matched groups and treated with radiation therapy (RT) or chemoradiation were included in this analysis: 6 grade 0 (group 0), 8 grade 1 (group 1), and 6 grade ≥ 2 RILT (group 2). Platelet poor plasma was obtained pre-RT, at 2-, 4-, 6-week during-RT, and 1-, 3-month post-RT. The plasma proteomic characterizations from patients with and without RILT were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography (RP-HPLC), and nano-LC electrospray tandem mass spectrometry (LC-ESI-MS/MS). ANOVA model was applied for significance test. Results: 23 common proteins were detected in all 20 patients, 9 of them, Ceruloplasmin, Prothrombin, Complement C3, Beta-2-glycoprotein (β2GP1) 1, Vitronectin, Complement factor I, Complement factor H, Complement C4-A, Complement C7, had significant difference among 3 groups. At baseline (Pre-RT), the levels of Vitronectin and C4-A in group 2 were both significantly higher than that in group 0 (p=0.008 and 0.021, respectively). At 2-week during RT, the levels of Ceruloplasmin, Prothrombin and β2GP1 in group 1 were significantly higher than that in group 0 (p=0.017, 0.011 and 0.013, respectively). At 4-week during RT, the levels of β2GP1 in group 1 and group 2 were significantly higher than that in group 0 (p=0.005 and 0.014). At 6-weeks during RT, Prothrombin, C3, Complement factor H, C7 and Complement factor I also had some significant changes among three groups. Conclusions: Plasma proteins related to inflammation, coagulation and fibrosis, such as β2GP1, change differently during RT in patients with and without RILT. This proteomic approach may identify new markers during treatment to predict RILT for adapting treatment to patient. Fundings: ASCO career developmental award, grant from Pardee foundation, and RTOG translational research program. No significant financial relationships to disclose.
DIFFERENCES AMONG AFRICAN AMERICANS AND WHITE PATIENTS UNDERGOING IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION FOR PRIMARY PREVENTION
Authors: Vishal Yogin Parikh, Kerolos Fahmi, Mrugesh Thakkar, Kevin Kip, Thanh Tran, Dany Sayad, Michael Fradley, Bengt Herweg, Sanders Chae
Journal: Journal of the American College of Cardiology (2017)
Abstract 19549: Automated External Defibrillation: Not That Easy! Untrained Laypeople Place AED Pads Poorly
Authors: Henrik Bødtker, Mathilde Stærk, Kasper G Lauridsen, André Jæger, Bo Løfgren
Journal: Circulation (2015)

Introduction: Public access defibrillation is recommended to increase survival. Automated external defibrillators (AED) have therefore been widely deployed and are available in public places. AEDs are claimed to be easy to use without requirements for training. The aim of this study was to investigate the ability of untrained laypersons to correctly place AED pads. Methods: Untrained laypeople were invited to participate. Participants were asked to operate a training AED (Lifepak® CR-T AED Trainer, PhysioControl) and place pads according to instructions fra the AED. Pads were placed on an anatomically realistic male resuscitation torso with arms (AMBU® Man, AMBU). Positioning of pads was digitally photographed and compared to the recommended pad position i.e. left apical pad in the left mid-axillary line, approximately level with the V6 ECG electrode and right sternal pad to the right of the sternum, below the clavicle. Digital data analysis was performed using ImageJ (version 1.46r) and distance from the center of the AED pads to the recommended pad position was calculated. Results: In total 40 volunteers (female: 60%, mean age 48.6 years) participated. The distance from the recommended left apical pad position was (median; 25% and 75% percentile) 8.6 (6.5; 10.4) cm while distance from the recommended right sternal pad position was (median; 25% and 75% percentile) 2.4 (1.6; 3.7) cm. In total, 95% of participants placed the left apical pad more than 5 cm from the recommended position. The right sternal pad was less often (12.5%, p&lt;0.0001) placed more than 5 cm away from recommended position. The left apical electrode was often placed too medial (Figure 1). Only, 12.5% of participants moved the left arm of the manikin to help place the left apical pad correctly. Conclusions: Untrained laypeople place AED pads poorly. The left apical pad is often misplaced medially. AED voice prompts and pad design should be further developed to guide untrained users to correct pad placement.
The chemokine network in normal and malignant cervix: CCR4 expression by malignant human cervical epithelial cells
Authors: Violet I F Slettenaar, Philippe O. Van Trappen, Yaohe Wang, Ayse Ayhan, Fiona N. Li, Fran Balkwill, Julia L. Wilson
Journal: Cancer Research (2006)

2810  Chemokines and their receptors play important roles in cancer biology influencing the movement of both stromal and malignant cells and modulating the expression of other cytokines, chemokines and proteases. In order to further understand the role of chemokines in cervical cancer the expression of twenty-three chemokines and fifteen chemokine receptors was investigated in normal and malignant cervix using a Rnase Protection Assay. The relative contribution of epithelial and stromal compartments in the chemokine network were assessed using low density gene-array and laser capture microdissection. Immunohistochemical staining was employed to validate and locate a tumour associated chemokine receptor in normal, pre-invasive and invasive cervical tissue and also on infiltrating cells. We found two key differences in chemokine receptor expression between normal and malignant tissue. First, mRNA for CX3CR1 was detected in normal cervical tissue, but was absent in malignant tissue. Second, higher expression of mRNA for CCR4 was detected in malignant cervical tissue compared to normal cervix. Both the stromal and epithelial compartments contributed to the high mRNA CCR4 expression. In normal cervical tissue, CCR4 protein expression was detected only on macrophages. However, in pre-malignant stages of cervical cancer (CIN) and invasive cervical tissues, CCR4 protein was not only detected on infiltrating macrophages and regulatory T cells but also, surprisingly, on tumour cells. The macrophage and regulatory T cell infiltration in samples of normal cervical tissue, pre-malignant lesions, and stages I, II and III of invasive epithelial cervical cancer were further characterized. Normal cervical tissue contained few, if any, macrophages and regulatory T cells. These numbers were increased in pre-malignant lesions and invasive cervical cancers. This data, to our knowledge, is the first description of CCR4 expression by malignant epithelial cells. Increased CCR4 expression in cervical cancer is also due to increased number of CCR4 expressing macrophages and regulatory T cells. The observation that CCR4 is expressed by the pre-malignant stages (CIN1, CINII and CINIII) of cervical cancer, may indicate that CCR4 expression may play an important, yet-undefined, role in early events of cervical carcinogenesis.
ASSOCIATION BETWEEN HOMEOSTASIS MODEL ASSESSMENT OF INSULIN RESISTANCE AND SURVIVAL IN DIABETIC PATIENTS WITH ACUTE CORONARY SYNDROMES: INSIGHTS FROM THE ALECARDIO TRIAL
Authors: Barbara E. Staehli, Anna Nozza, Ilse C. Schrieks, Klas Malmberg, Bruce Neal, Stephen Nicholls, Linda Mellbin, Anders Svensson, Hans Wedel, Arlette Weichert, A. Michael Lincoff, Diederick Grobbee, Jean-Claude Tardif, Gregory Schwartz
Journal: Journal of the American College of Cardiology (2017)
DETECTION OF HEART FAILURE WITH PRESERVED EJECTION FRACTION IN SINGLE VENTRICLE PHYSIOLOGY: INSIGHTS FROM THE PEDIATRIC HEART NETWORK FONTAN CROSS-SECTIONAL STUDY PUBLIC USE DATASET
Authors: Shahryar Chowdhury, Eric Graham, Carolyn Taylor, Geoffrey Forbus, Andrew Savage, Andrew Atz
Journal: Journal of the American College of Cardiology (2017)
A risk-adapted study of cisplatin and etoposide, with or without ifosfamide, in patients with metastatic seminoma: Results of the GETUG S99 multicenter prospective study
Authors: K. Fizazi, M. Aubelle, R. Delva, C. Chevreau, A. Caty, P. Kerbrat, F. Rolland, F. Priou, A. Laplanche
Journal: Journal of Clinical Oncology (2009)

5031 Background: Cisplatin plus etoposide-based chemotherapy is the recommended treatment and results in a high cure rate in patients (pts) with metastatic seminoma (Eur Urol 2008, 53: 478–96). Whether pts with good-prognosis and intermediate-prognosis metastatic seminoma should be treated differently or not has not been defined. Methods: From December 1999 to September 2008, pts with pure seminoma, a normal serum alpha-feto protein value, and evidence of metastases were included in this prospective study. Pts with a good prognosis according to the IGGCCG classification were treated with 4 cycles of EP (cisplatin 20 mg/m 2 /day and etoposide 100 mg/m 2 /day x 5 days, every 3 weeks). Pts with an intermediate prognosis according to the IGCCCG or MRC classifications (extra-pulmonary visceral metastases or supra-diaphragmatic metastases plus serum LDH&gt; 2 x N) (J Clin Oncol. 1997;15:594–603; Eur J Cancer. 1999;33:1347–1350) were treated with 4 cycles of VIP + G-CSF (cisplatin 20 mg/m 2 /day, ifosfamide 1.2 g/m 2 /day, and etoposide 75 mg/m 2 /day x 5 days, every 3 weeks + G-CSF). Toxicity was assessed using the NCI-CTC scale. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 133 pts were included in this study. Median age was 36 years (20–66). The median follow-up is 3.6 years (0.4–9.1). 110 (83%) pts had good-prognosis metastatic seminoma and received EP. Grade 3–4 toxicity included mainly neutropenia (41%) and neutropenic fever (13%). The 3-year PFS rate in good-prognosis pts is 94% (87–97), and the OS rate is 99% (94–100). 23 (17%) pts had intermediate-prognosis disease and received VIP + G-CSF. Toxicity included grade 3–4 neutropenia (32%), neutropenic fever (18%), grade 3–4 thrombocytopenia (18%), and grade 3–4 anemia (19%). Platelet and erythrocyte transfusions were required in 32% and 36% of pts, respectively . The 3-year PFS rate is 86% (67–95), and the OS rate is 91% (72–97) in intermediate-prognosis pts. Overall, 92 pts (69%) had post-chemotherapy residual masses and 75 pts (56%) were managed with 18 Flurorodeoxyglucose positron emission tomography. Conclusions: This risk-adapted chemotherapy yielded an excellent outcome with an OS rate of 97% in metastatic seminoma. No significant financial relationships to disclose.
Palonosetron (PALO) + dexamethasone (DEX) for prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) in patients receiving multiple-day cisplatin CT for germ cell cancer
Authors: M. J. Brames, B. J. Roth, R. Dreicer, J. Bubalo, C. Nichols, M. T. Cullen, T. Degroot, L. H. Einhorn
Journal: Journal of Clinical Oncology (2006)

8607 Background: Fractionated cisplatin is highly emetogenic; despite 5HT 3 receptor antagonists + DEX, patients still experience acute and delayed CINV. PALO, a novel 5HT 3 antagonist, is superior to conventional 5HT 3 antagonists in protecting patients from emesis with a 0.25-mg IV dose prior to single-day CT. To assess the efficacy and safety of PALO in 40 patients with germ cell tumors receiving multiple-day cisplatin-based CT, a phase II multicenter study is being conducted. Methods: Adult men receiving 5-day cisplatin-based (20 mg/m 2 /d) CT received PALO 0.25 mg IV 30 min before CT on days 1, 3, and 5 and DEX 20 mg qd (po or IV 30 min before CT) on days 1–2; 8 mg po bid on days 6–7; and 4 mg po bid on day 8. Rescue medication was allowed at investigator discretion. Endpoints included emetic episodes (EE), nausea intensity, and rescue use, recorded in diaries for 9 consecutive 24-h periods. Interference with functioning due to nausea on a 4-point scale (none, a little bit, quite a bit, very much) was assessed with the validated Osoba nausea module on days 1, 5, and 10; safety was assessed at all follow-up encounters. Results: To date, 32 patients are evaluated, median age 35 years, 81% CT-naïve. Prior to CT, 97% of patients reported no more than a little interference with functioning from nausea. Most patients reported no significant interference with functioning due to nausea on days 1–4 of cisplatin (73% reported none/a little bit) and days 5–9 (87% none/a little bit). PALO + DEX was well tolerated; treatment-related adverse events were mild-moderate headache (18.8%), constipation (6.3%), and abdominal pain (3.1%), none serious. Conclusions: Three doses of PALO + 5 doses of DEX over an 8-day period effectively prevented both emesis and significant nausea in the majority of patients with germ cell tumors receiving multiple-day cisplatin-based CT. This regimen appears to be an improvement over historical CINV control. [Table: see text] [Table: see text]
Reaching complete or near-complete resolution of psoriasis: benefit and risk considerations
Authors: A. Blauvelt, C.E.M. Griffiths, M. Lebwohl, U. Mrowietz, L. Puig, S. Ball, L. Zhang, E. Edson-Heredia, M. Warner, B. Zhu, C-Y. Lin, E. Nikaï, D. Dey, L. Mallbris, K. Reich
Journal: British Journal of Dermatology (2017)
Early diagnosis of mild cognitive impairment and mild dementia through basic and instrumental activities of daily living: Development of a new evaluation tool
Authors: Elise Cornelis, Ellen Gorus, Ingo Beyer, Ivan Bautmans, Patricia De Vriendt
Journal: PLoS Medicine (2017)

Background Assessment of activities of daily living (ADL) is paramount to determine impairment in everyday functioning and to ensure accurate early diagnosis of neurocognitive disorders. Unfortunately, most common ADL tools are limited in their use in a diagnostic process. This study developed a new evaluation by adopting the items of the Katz Index (basic [b-] ADL) and Lawton Scale (instrumental [i-] ADL), defining them with the terminology of the International Classification of Human Functioning, Disability and Health (ICF), adding the scoring system of the ICF, and adding the possibility to identify underlying causes of limitations in ADL. Methods and findings The construct validity, interrater reliability, and discriminative validity of this new evaluation were determined. From 2015 until 2016, older persons (65–93 y) with normal cognitive ageing (healthy comparison [HC]) (n = 79), mild cognitive impairment (MCI) (n = 73), and Alzheimer disease (AD) (n = 71) underwent a diagnostic procedure for neurocognitive disorders at the geriatric day hospital of the Universitair Ziekenhuis Brussel (Brussels, Belgium). Additionally, the ICF-based evaluation for b- and i-ADL was carried out. A global disability index (DI), a cognitive DI (CDI), and a physical DI (PDI) were calculated. The i-ADL-CDI showed high accuracy and higher discriminative power than the Lawton Scale in differentiating HC and MCI (area under the curve [AUC] = 0.895, 95% CI .840–.950, p = .002), MCI and AD (AUC = 0.805, 95% CI .805–.734, p = .010), and HC and AD (AUC = 0.990, 95% CI .978–1.000, p < .001). The b-ADL-DI showed significantly better discriminative accuracy than the Katz Index in differentiating HC and AD (AUC = 0.828, 95% CI .759–.897, p = .039). This study was conducted in a clinically relevant sample. However, heterogeneity between HC, MCI, and AD and the use of different methods of reporting ADL might limit this study. Conclusions This evaluation of b- and i-ADL can contribute to the diagnostic differentiation between cognitively healthy ageing and neurocognitive disorders in older age. This evaluation provides more clarity and nuance in assessing everyday functioning by using an ICF-based terminology and scoring system. Also, the possibility to take underlying causes of limitations into account seems to be valuable since it is crucial to determine the extent to which cognitive decline is responsible for functional impairment in diagnosing neurocognitive disorders. Though further prospective validation is still required, the i-ADL-CDI might be useful in clinical practice since it identifies impairment in i-ADL exclusively because of cognitive limitations.
Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections
Authors: Jingjing Zhang, Ida M. Friberg, Ann Kift-Morgan, Gita Parekh, Matt P. Morgan, Anna Rita Liuzzi, Chan-Yu Lin, Kieron L. Donovan, Chantal S. Colmont, Peter H. Morgan, Paul Davis, Ian Weeks, Donald J. Fraser, Nicholas Topley, Matthias Eberl
Journal: Kidney International (2017)

The immune system has evolved to sense invading pathogens, control infection, and restore tissue integrity. Despite symptomatic variability in patients, unequivocal evidence that an individual's immune system distinguishes between different organisms and mounts an appropriate response is lacking. We here used a systematic approach to characterize responses to microbiologically well-defined infection in a total of 83 peritoneal dialysis patients on the day of presentation with acute peritonitis. A broad range of cellular and soluble parameters was determined in peritoneal effluents, covering the majority of local immune cells, inflammatory and regulatory cytokines and chemokines as well as tissue damage-related factors. Our analyses, utilizing machine-learning algorithms, demonstrate that different groups of bacteria induce qualitatively distinct local immune fingerprints, with specific biomarker signatures associated with Gram-negative and Gram-positive organisms, and with culture-negative episodes of unclear etiology. Even more, within the Gram-positive group, unique immune biomarker combinations identified streptococcal and non-streptococcal species including coagulase-negative Staphylococcus spp. These findings have diagnostic and prognostic implications by informing patient management and treatment choice at the point of care. Thus, our data establish the power of non-linear mathematical models to analyze complex biomedical datasets and highlight key pathways involved in pathogen-specific immune responses.
Outcome of Stem Cell Transplantation in Adults with Acute Myelogenous Leukemia and Normal Cytogenetics (NC-AML) According to Presence of FLT-3 Internal Tandem Duplication (FLT-3ITD) At the Time of Diagnosis
Authors: Ellin Berman, Ann A Jakubowski, Molly Maloy, Joseph G. Jurcic, Suresh C. Jhanwar, Cyrus V. Hedvat, Sergio Giralt, Esperanza B. Papadopoulos
Journal: Blood (2012)
Contents Vol. 81, 2012
Authors: Elena Tomba, Per Bech, Carlotta Belaise, Alessia Gatti, Virginie-Anne Chouinard, Guy Chouinard, Piero Porcelli, Domenico Laera, Domenico Mastrangelo, Angelo Di Masi, Christian Fazekas, Anton Leitner, Antonio Tundo, Andrea Murru, Isabella Pacchiarotti, Alessandra M.A. Nivoli, Francesc Colom, Eduard Vieta, Giovanni Castellini, Lorenzo Lelli, Carolina Lo Sauro, Linda Vignozzi, Mario Maggi, Carlo Faravelli, Anton J.L.M. van Balkom, Paul M.G. Emmelkamp, Merijn Eikelenboom, Adriaan W. Hoogendoorn, Johannes H. Smit, Patricia van Oppen, Gerhard Andersson, Björn Paxling, Pie Roch-Norlund, Gunnar Östman, Anna Norgren, Jonas Almlöv, Lisa Georén, Elisabeth Breitholtz, Mats Dahlin, Pim Cuijpers, Per Carlbring, Farrell Silverberg, Umberto Albert, Andrea Aguglia, Filippo Bogetto, Luca Cieri, Marinella Daniele, Giuseppe Maina, Roberta Necci, Anita Parena, Loretta Salvati, Valdo Ricca, Elena Tomba, Emanuela Offidani, Stefan Priebe, Nyla Bhatti, Kirsten Barnicot, Stephen Bremner, Amy Gaglia, Christina Katsakou, Iris Molosankwe, Paul McCrone, Martin Zinkler, Sarah E. Kirby, Lucy Yardley, Andreas Joos, Barbara Saum, Armin Hartmann, Oliver Tüscher, Ludger Tebartz van Elst, Almut Zeeck, Mark Zimmerman, Satz Mengensatzproduktion, Druck Reinhardt Druck Basel, Druck Reinhardt Druck Basel
Journal: Psychotherapy and Psychosomatics (2012)
MYOCARDIAL OXYGENATION USING BLOOD LEVEL-OXYGEN DEPENDENT SEQUENCE IN MAGNETIC RESONANCE DETERMINES MYOCARDIAL ENERGETICS AND CAPILLARY DENSITY
Authors: Carlos G. Santos-Gallego, Ida U. Njerve, Belen Picatoste, Kiyotake Ishikawa, Roger Hajjar, Valentin Fuster, Angel Sanz Salvo, Juan Badimon
Journal: Journal of the American College of Cardiology (2017)
IMPACT OF CARDIAC DEVICES ON READMISSION AND SHORT TERM MORTALITY IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION: A NATIONWIDE STUDY
Authors: Varun Kumar, Byomesh Tripathi, Shilpkumar Arora, Prashant Patel, Sopan Lahewala, Chirag Savani, Nilay Patel, Harshil Shah, Umesh Gidwani, Apurva Badheka, Abhishek Deshmukh, Alan Rozanski, Radha Gopalan
Journal: Journal of the American College of Cardiology (2017)