tbuckley/cabot-search huggingface dataset:
The patellofemoral pain and osteoarthritis subscale of the KOOS (KOOS-PF): development and validation using the COSMIN checklist
Authors: Kay M Crossley, Erin M Macri, Sallie M Cowan, Natalie J Collins, Ewa M Roos
Journal: British Journal of Sports Medicine (2017)

Patellofemoral pain and osteoarthritis are prevalent and associated with substantial pain and functional impairments. Patient-reported outcome measures (PROMs) are recommended for research and clinical use, but no PROMs are specific for patellofemoral osteoarthritis, and existing PROMs for patellofemoral pain have methodological limitations. This study aimed to develop a new subscale of the Knee injury and Osteoarthritis Outcome Score for patellofemoral pain and osteoarthritis (KOOS-PF), and evaluate its measurement properties.Items were generated using input from 50 patients with patellofemoral pain and/or osteoarthritis and 14 health and medical clinicians. Item reduction was performed using data from patellofemoral cohorts (n=138). We used the COnsesus-based Standards for the selection of health Measurements INstruments guidelines to evaluate reliability, validity, responsiveness and interpretability of the final version of KOOS-PF and other KOOS subscales.From an initial 80 generated items, the final subscale included 11 items. KOOS-PF items loaded predominantly on one factor, pain during activities that load the patellofemoral joint. KOOS-PF had good internal consistency (Cronbach's α 0.86) and adequate test-retest reliability (intraclass correlation coefficient 0.86). Hypothesis testing supported convergent, divergent and known-groups validity. Responsiveness was confirmed, with KOOS-PF demonstrating a moderate correlation with Global Rating of Change scores (r 0.52) and large effect size (Cohen's d 0.89). Minimal detectable change was 2.3 (groups) and 16 (individuals), while minimal important change was 16.4. There were no floor or ceiling effects.The 11-item KOOS-PF, developed in consultation with patients and clinicians, demonstrated adequate measurement properties, and is recommended for clinical and research use in patients with patellofemoral pain and osteoarthritis.
Phage therapy is highly effective against chronic lung infections with<i>Pseudomonas aeruginosa</i>
Authors: Elaine M Waters, Daniel R Neill, Basak Kaman, Jaspreet S Sahota, Martha R J Clokie, Craig Winstanley, Aras Kadioglu
Journal: Thorax (2017)

With an increase in cases of multidrug-resistant <i>Pseudomonas aeruginosa</i>, alternative and adjunct treatments are needed, leading to renewed interest in bacteriophage therapy. There have been few clinically relevant studies of phage therapy against chronic lung infections. Using a novel murine model that uses a natural respiratory inhalation route of infection, we show that phage therapy is an effective treatment against chronic <i>P. aeruginosa</i> lung infections. We also show efficacy against <i>P. aeruginosa</i> in a biofilm-associated cystic fibrosis lung-like environment. These studies demonstrate the potential for phage therapy in the treatment of established and recalcitrant chronic respiratory tract infections.
Resuscitation policy should focus on the patient, not the decision
Authors: Zoë Fritz, Anne-Marie Slowther, Gavin D Perkins
Journal: BMJ (2017)

Zoë Fritz and colleagues discuss new approaches to resuscitation decisions that incorporate broader goals of care Do not attempt cardiopulmonary resuscitation (DNACPR) decisions are made commonly in healthcare but can be a source of ethical concern and legal challenge. They differ from other healthcare decisions because they are made in anticipation of a future event and concern withholding, rather than giving, a treatment. DNACPR decisions were introduced to protect patients from invasive treatments that had little or no chance of success. However, inconsistencies in decision making, communication, and documentation have led to misunderstandings about what DNACPR means and to delivery of poorer care to some patients. Here we discuss the problems with current practice and outline newer approaches that place the patient, and their family, at the centre of the discussions. We focus on overall treatment plans and supporting clinicians and patients to make shared decisions about emergency treatments. CPR is an invasive medical treatment that was never intended to be given to patients who are dying from an irreversible condition.1 DNACPR decisions provide a way of communicating when patients should not receive CPR, either because they do not want it or because it has little chance of success (box 1). They are an important mechanism for protecting patients from harm, but they have taken on practical, legal, and emotional significance far beyond their intended remit.6 #### Box 1: Clinical context of CPR and DNACPR
Exercise training may improve the tumour microenvironment after breast cancer (PEDro synthesis)
Authors: Vincent Singh Paramanandam, Vincent S Prema
Journal: British Journal of Sports Medicine (2017)

Meneses-Echavez JF, Correa-Bautista JE, Gonzalez-Jimenez E, et al . Cancer Epidemiol Biomarkers Prev . 2016;25:1009–17.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in women worldwide.1 Many studies show a relationship between exercise behaviour and breast cancer prognosis. Additionally, more recent research reports a relationship between fitness and disease-free survival in women with breast cancer.2 However, there is paucity of evidence exploring the various mechanisms underlying the exercise-prognosis relationship in cancer. This systematic review addressed one possible mechanism: the effect of exercise training on inflammatory mediators.

This systematic review aimed to quantitatively analyse the effect of exercise training on inflammatory biomarkers in breast cancer survivors.

PubMed, CENTRAL, Embase and Scopus were searched with search terms related to breast cancer, exercise and inflammatory mediators. In addition, six relevant journals and conference abstracts from the American Society of Clinical Oncology website from 2004 to 2013 were searched. Moreover, reference lists of the included studies were examined, and …
OP17. MEASURING AND MODIFYING TEMOZOLOMIDE DELIVERY IN BRAIN TUMOURS
Authors: Dr Ibrahim Djoukhadar, Dr Marie-claude Asselin, Prof Kaye Williams, Prof Alan Jackson
Journal: Neuro-Oncology (2017)

INTRODUCTION: Malignant brain tumours constitute a fatal diagnosis with 5-year survival rates of less than 5%. Temozolomide (TMZ) is the central chemotherapy agent used in the treatment of malignant brain tumours; however, despite aggressive treatment approaches outcomes are still poor with many patients developing chemoresistance. P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are the main efflux transporters implicated in the development of chemoresistance. Furthermore, P-gp and BCRP appear to work closely together as anticancer efflux pumps. Interestingly, the relationship between TMZ and P-gp and BCRP remains poorly understood. In this work we aim to evaluate the roles of P-gp and BCRP in restricting TMZ delivery into the brain and evaluate the effects of P-gp and BCRP inhibition on the delivery of TMZ in a glioma model in mice. METHODS: TMZ drug transport experiments were performed in a porcine derived and validated in-vitro blood-brain barrier model. In-vivo Positron Emission Tomography (PET) imaging studies with [11C]TMZ in wild type mice and in mice lacking P-gp, BCRP or both transporters. Similar PET studies with [11C]TMZ were conducted in wild type mice with and without the chemical inhibition of P-gp and BCRP. Finally, a human glioma model in mice was derived by intracranial injection of human U87 glioma cells in thirty-five athymic female mice. Animals were treated with TMZ alone (50 mg/kg), Tariquidar alone (TQD; a potent P-gp and BCRP inhibitor – 40 mg/kg) or combination therapy (TMZ and TQD). Control animals received vehicle solution only. Response to treatment was evaluated by performing volumetric tumour measurement using Magnetic Resonance Imaging (MRI). RESULTS: In-vitro transport experiments showed a trend for TMZ to be transported P-gp and BCRP. PET scans confirmed higher delivery [11C]TMZ in mice lacking P-gp, BCRP and both transporters. Similar results were noted in wild type animals following the chemical inhibition of P-gp and BCRP. In U87 glioma model experiments; both TMZ alone and combination therapy resulted in a significant glioma response when compared with the control and the TQD alone treatment groups. Moreover, combination therapy resulted in a significantly superior response when compared with TMZ alone treatment. CONCLUSION: Our combined in-vitro and in-vivo data confirms TMZ as a weak substrate for both P-gp and BCRP at the blood-brain barrier. Furthermore, P-gp and BCRP inhibition may be a suitable strategy for modifying TMZ delivery in brain tumours that warrants further investigations.
Functional and Genomic Signatures of Homologous Recombination (HR) Predict for Clinical Outcome in Multiple Myeloma (MM)
Authors: Masood A Shammas, Subodh Kumar, Purushothama Nanjappa, Mehmet K Samur, Srikanth Talluri, Jianhong Lin, Florence Magrangeas, Stephane Minvielle, Hervé Avet-Loiseau, Nikhil C. Munshi
Journal: Blood (2015)
Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity
Authors: Malini Ahuja, Daniella M. Schwartz, Mayank Tandon, Aran Son, Mei Zeng, William Swaim, Michael Eckhaus, Victoria Hoffman, Yiyuan Cui, Bo Xiao, Paul F. Worley, Shmuel Muallem
Journal: Cell Metabolism (2017)
Accurate and equitable medical genomic analysis requires an understanding of demography and its influence on sample size and ratio
Authors: Michael D. Kessler, Timothy D. O’Connor
Journal: Genome biology (2017)

In a recent study, Petrovski and Goldstein reported that (non-Finnish) Europeans have significantly fewer nonsynonymous singletons in Online Mendelian Inheritance in Man (OMIM) disease genes compared with Africans, Latinos, South Asians, East Asians, and other unassigned non-Europeans. We use simulations of Exome Aggregation Consortium (ExAC) data to show that sample size and ratio interact to influence the number of these singletons identified in a cohort. These interactions are different across ancestries and can lead to the same number of identified singletons in both Europeans and non-Europeans without an equal number of samples. We conclude that there is a need to account for the ancestry-specific influence of demography on genomic architecture and rare variant analysis in order to address inequalities in medical genomic analysis. The authors of the original article were invited to submit a response, but declined to do so. Please see related Open Letter: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1016-y
Familial Platelet Disorder and Predisposition to Myeloid Leukemia (FPD/AML) in the Absence of RUNX1 Mutations- A Report of Three Families.
Authors: Jason N. Berman, Stephen Couban, Allan Ebbin, Haydar Frangoul, Maria B. Quisumbing, Thomas E Aikie, Christie Riddell, Meghan Ferguson, Mark D. Ludman, Conrad V. Fernandez, Alan B. Cantor
Journal: Blood (2009)
Pru p 3, a marker allergen for lipid transfer protein sensitization also in Central Europe
Authors: N. Mothes‐Luksch, M. Raith, G. Stingl, M. Focke‐Tejkl, E. Razzazi‐Fazeli, R. Zieglmayer, S. Wöhrl, I. Swoboda
Journal: Allergy (2017)

Abstract In the Mediterranean area, lipid transfer proteins ( LTP s) are important causes of plant‐food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract‐based diagnosis is often complicated by co‐sensitization to Bet v 1, the major birch pollen allergen, its cross‐reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant‐derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant‐food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients.
Measurement of troponin and natriuretic peptides shortly after admission in patients with heart failure—does it add useful prognostic information? An analysis of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (<scp>VERITAS</scp>)
Authors: John G.F. Cleland, John R. Teerlink, Beth A. Davison, Ahmad Shoaib, Marco Metra, Stefanie Senger, Olga Milo, Gad Cotter, Robert C. Bourge, John D. Parker, Guillaume Jondeau, Henry Krum, Christopher M. O'Connor, Guillermo Torre‐Amione, Dirk J. van Veldhuisen, John J.V. McMurray
Journal: European Journal of Heart Failure (2017)
MDM2 Dependant Induction of Error Prone DNA Polymerase beta by EBV-LMP1 Oncoprotein.
Authors: Faumont Nathalie, Le Clorennec Christophe, Teira Pierre, Youlyouz-Marfak Ibtissam, Mazeres Christine, Hoffmann Jean Sebastien, Delsol Georges, Feuillard Jean, Meggetto Fabienne
Journal: Blood (2005)
Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – Updated Results with Encouraging Progression Free Survival (PFS) Data From a Phase II Study In Patients with Relapsed/Refractory Indolent NHL (iNHL)
Authors: Gilles Andre Salles, Franck Morschhauser, Catherine Thieblemont, Philippe Solal-Céligny, Thierry Lamy, Herve Tilly, Pierre Feugier, Steven Le Gouill, Emmanuel Gyan, Reda Bouabdallah, Michael Wenger, Joe Birkett, Guillaume Cartron
Journal: Blood (2010)
Role of IκBα as a negative regulator of EGFR and a molecular determinant of prognosis in glioblastoma multiforme
Authors: M. Bredel, J. Renfrow, A. Yadav, A. Alvarez, D. Lin, D. Scholtens, X. He, J. Chandler, A. Scheck, G. Harsh
Journal: Journal of Clinical Oncology (2009)

2028 Background: Glioblastoma multiforme is a complex disease that involves the deregulation of overlapping signaling pathways. Constitutive activation of the transcription factor nuclear factor-κB (NF-κB) has been broadly associated with various human cancers, including glioblastomas, and their therapy resistance and may be due to cross-coupling with other oncogenic pathways, such as epidermal growth factor signaling. Methods: Multidimensional analysis involving gene and transcript data for the endogenous NF-κB modulator IκBα/NFKBIA and clinical patient profiles of 482 glioblastomas/high-grade gliomas from multiple institutions in the United States and The Cancer Genome Atlas Pilot Project. Functional analyses using LN229, U87, and U118 glioblastoma cells, and human embryonic kidney 293T cells with transgene phenotypes for IκBα. IκBα promoter and coding sequence and promoter methylation analyses in a resistance model of 15 glioblastomas cell lines with in vitro and/or in vivo resistance to O6-alkylating agents. Results: We have identified a regulatory circuit between NF-κB and EGFR signaling in glioblastomas, where IκBα binds to EGFR and attenuates EGFR signaling by immobilizing its kinase domain into an inactive conformation. We found the NFKBIA gene at 14q13.2 deleted in 25% of glioblastomas and its occurrence mutually exclusive with EGFR amplification. Loss of NFKBIA associates independently with patient survival. Functional analyses uncover a bona fide tumor suppressor role for IκBα in glioblastoma cells, where it functions to constrain tumorigenic and migratory potential, and induce spontaneous cellular senescence, and apoptosis in response to treatment. IκBα expression is an independent predictor of patient prognosis in multiple glioblastoma populations. Glioblastomas with initially high IκBα expression significantly repress IκBα upon tumor recurrence, suggesting an acquired mechanism to evade its tumor-suppressive and/or chemo-sensitizing effects during tumor progression. Conclusions: IκBα is a molecular determinant of biological tumor behavior and patient survival in glioblastoma multiforme. Deletion of NFKBIA could present an alternate mechanism to activate EGFR signaling in EGFR non-amplified glioblastomas. No significant financial relationships to disclose.
Abstract P5-10-09: Prospective cross-sectional-study on participation in mammography screening according to immigration background and education status
Authors: E Kuehnle, T Oeztuerk, W Siggelkow, K Luebbe, A Moser, S Noeding, J John, T Noesselt, C Busch, M Arfsten, S Lemster, P Hillemans, T Doerk, T-W Park-Simon
Journal: Cancer Research (2017)

Abstract Introduction Although the health of immigrants is an important issue in national health care policy there is a serious shortage of data in many countries. Most studies lack information on educational status which is a major limitation. In this prospective cross-sectional-study we analyzed the influence of immigration background and educational status on the participation in mammography screening programs in Lower-Saxony, Germany. Material and methods Data collection was conducted from 2012-2016 in six certified breast cancer centers using a personal questionnaire and data from the patients' medical records. Stratification into subgroups was carried out according to first and second generation immigrants and country of origin. Results 1547/2129 primary breast cancer cases were analyzed. The percentage of patients with a history of immigration in our study cohort was 17.7%. The majority of them were citizens of EU27 Member states. First generation immigrants (n= 146), second generation immigrants (n=129), natives (n= 1272). No significant difference was seen in sex, age, tumor stage, histology, grading, Ki-67, Her2/neu-status, and hormone receptor status. A 100% participation rate in the mammography screening program was seen in patients with no school graduation. The lowest participation rate (85.5%) was seen in the group of native Germans with a college graduation and in first generation immigrants with a high school graduation (86.7%). Detailed statistical analysis will be presented on the poster. Conclusion No difference was seen between immigrants and native Germans with regard to tumor biology. In first-generation immigrants mammography screening was well accepted despite cultural and linguistic differences. Participation rate decreased with higher education level in all groups. High school graduates with immigrant background participated more frequently in breast cancer screening than native high school graduates. These findings mainly relate to immigrants from EU27 Member states rather than immigrants from non EU countries. Citation Format: Kuehnle E, Oeztuerk T, Siggelkow W, Luebbe K, Moser A, Noeding S, John J, Noesselt T, Busch C, Arfsten M, Lemster S, Hillemans P, Doerk T, Park-Simon T-W. Prospective cross-sectional-study on participation in mammography screening according to immigration background and education status [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-10-09.
Placenta Derived Adherent Cells Modulate the Allogenic Mixed Lymphocyte Reaction Partially via an Indoleamine 2,3-Dioxygenase Mediated Mechanism.
Authors: Bitao Liang, Casper Paludan, Matthew Downey, Craig Lewis, Ryhor Harbacheuski, Hemlata Rana, Chris Lugo, Xiaohua Lu, Tara Lakatos, Wei Wu, James Edinger
Journal: Blood (2007)
Erratum: Imaging techniques for the diagnosis of hepatocellular carcinoma. A systematic review and meta-analysis (Annals of Internal Medicine (2015) 162 (697-711) DOI: 10.7326/M14-2509)
Authors: R. Chou, C. Cuevas, R. Fu, B. Devine, N. Wasson, A. Ginsburg
Journal: Annals of Internal Medicine (2015)
Long-Term Follow-Up of Patients Treated with Bortezomib Alone and in Combination with Dexamethasone as Frontline Therapy for Multiple Myeloma.
Authors: Sundar Jagannath, Brian G.M. Durie, Jeffrey Lee Wolf, Elber S. Camacho, David Irwin, Jose Lutzky, Marti McKinley, Afshin Eli Gabayan, Amitabha Mazumder, John Crowley, Robert Vescio
Journal: Blood (2006)
Phosphoproteomic Landscaping Unveils Constitutive cKIT Activation in Human Erythroblasts from Polycythemia Vera (PV) Patients
Authors: Lilian Varricchio, Giulia Federici, Francesca Masiello, Fabrizio Martelli, Mario Falchi, Orietta Picconi, Gabriella Girelli, Agostino Tafuri, Emanuel Petricoin III, Ann Zeuner, Anna Rita Migliaccio
Journal: Blood (2016)
a Phase 2 Study of Alemtuzumab-Ofatumumab (A+O) Combination in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Authors: Shuo Ma, Steven T. Rosen, Olga Frankfurt, Jane N. Winter, Jennifer Kreutzer, Sonja Husa, Anders Österborg, Jeanette Lundin
Journal: Blood (2014)
Universal CD160 Expression and the CD5+23+ / CD5+19+ Ratio in Chronic Lymphocytic Leukemia Simplfy Identification of Atypical Cases from CD23+ Mantle Cell Lymphoma.
Authors: Dimitris A. Tsitsikas, Jerrome Giustiniani, Anne Skipper, Fatema Ebrahim, Ulrika Johannson, Marion Macey, Michael Jenner, Adrian C. Newland, Samir G. Agrawal
Journal: Blood (2007)
Abstract P5-07-04: Transition from a pre-malignant lesion to cancer does not require stemness of the cancer-originating cells in the lesion
Authors: W Bu, Y Li
Journal: Cancer Research (2017)

Abstract The precancerous lesion is the final step before malignancy, and is thus a key step to cancer prevention. Precancerous lesions are heterogeneous harboring distinct subsets of cells from stem cells to differentiated cells. Whether the stem cells or other subsets in these precancerous lesions are responsible for the eventual cancer remains unanswered. Here, we report that in the precancerous lesions of the MMTV-Wnt1 model of basal-like breast cancer, there exist the stem cell-enriched keratin 6a+ subset and more differentiated WAP+ cell subset. We demonstrate that both mutated Ras and B-Raf can robustly transform both cell subsets into cancer. These data suggest that multiple cell subsets in precancerous early lesions can evolve into cancer. This finding indicates that cancer prevention should target both self-renewing cells and other cell subsets in developing precancerous lesions in high-risk individuals. Citation Format: Bu W, Li Y. Transition from a pre-malignant lesion to cancer does not require stemness of the cancer-originating cells in the lesion [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-07-04.
Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial
Authors: Jeffrey A Jones, Tadeusz Robak, Jennifer R Brown, Farrukh T Awan, Xavier Badoux, Steven Coutre, Javier Loscertales, Kerry Taylor, Elisabeth Vandenberghe, Malgorzata Wach, Nina Wagner-Johnston, Loic Ysebaert, Lyndah Dreiling, Ronald Dubowy, Guan Xing, Ian W Flinn, Carolyn Owen
Journal: The Lancet Haematology (2017)