tbuckley/cabot-search huggingface dataset:
High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Øyvind Ellingsen, Martin Halle, Viviane Conraads, Asbjørn Støylen, Håvard Dalen, Charles Delagardelle, Alf-Inge Larsen, Torstein Hole, Alessandro Mezzani, Emeline M. Van Craenenbroeck, Vibeke Videm, Paul Beckers, Jeffrey W. Christle, Ephraim Winzer, Norman Mangner, Felix Woitek, Robert Höllriegel, Axel Pressler, Tea Monk-Hansen, Martin Snoer, Patrick Feiereisen, Torstein Valborgland, John Kjekshus, Rainer Hambrecht, Stephan Gielen, Trine Karlsen, Eva Prescott, Axel Linke
Journal: Circulation (2017)

Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE).Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks.Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT.HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.
ASYMPTOMATIC ELITE YOUNG TENNIS PLAYERS SHOW LATERAL AND VENTRAL GROWTH PLATE ALTERATIONS OF PROXIMAL HUMERUS ON MRI
Authors: Fredrik Johansson, Eva Skilgate, Edin Debri, Anders Adolfsson, Göran Jenner, Leif Swärd, Ann Cools
Journal: British Journal of Sports Medicine (2017)

Background The cartilage of the epiphyseal plate might be 2–5 times weaker than surrounding fibrous tissue; therefore epiphyseal (growth) plates are very sensitive to their surrounding mechanical environment. Objective The specific aim of the study was to investigate and compare epiphyseal length and extension in the proximal humerus, closure in the growth plate and bone marrow signal intensity related to the proximal humeral physis in the dominant arm and the non-dominant arm of the asymptomatic adolescent elite tennis player. Design Cross-sectional study. According to a pre-defined protocol including measurements of epiphyseal extension, epiphyseal length, closure of the growth plate and bone marrow signal intensity related to the proximal humeral physis the MRI scans were evaluated. Setting The study was an independent complement to the national high-performance program conducted by the Swedish Tennis Association. Patients (or Participants) Our study sample included 35 asymptomatic elite young tennis players (15 male, 20 female, mean age 17.4 years ±2.7). Interventions (or Assessment of Risk Factors) Each player contributed with two shoulders to the MRI evaluation. The non-dominant arm was used as a control. Two fellowship-trained musculoskeletal radiologists independently from each other reviewed magnetic resonance images. Main Outcome Measurements Epiphyseal extension and length, closure in the growth plate and bone marrow signal intensity related to the proximal humeral physis in the dominant arm (DA) and the non-dominant arm (NDA). Results Statistically significant differences between dominant arm and non-dominant arm in epiphyseal length (mm) laterally (DA 27.33 vs NDA 26.70) were shown. Statistically significant differences were also found in epiphyseal extension (mm) laterally (DA 36.10 vs NDA 35.10) and ventrally (DA 36.23 vs NDA 34.76). Conclusions Significant findings assessing MRI measurements of the epiphyseal plate in the asymptomatic adolescent elite tennis player might reflect a development of consecutive alterations in the epiphyseal plate in the dominant arm.
Clinical and pathological characteristics of triple-negative breast cancer patients: A single-center experience.
Authors: Aydan Akdeniz, Selim Yalcin, Samed Rahatli, Nadire Kucukoztas, Mahmut Can Yagmurdur, Omer Dizdar, Ozden Altundag, Ozgur Ozyilkan
Journal: Journal of Clinical Oncology (2012)

e11515 Background: Triple negative breast cancer in which estrogen, progesterone receptors and c-erbB2 overexpression are negative, seems to have different clinical course and recurrence pattern. Methods: We evaluated retrospectively clinical demographic and pathological characteristics of triple negative breast cancers and investigated the association of these characteristics with OS and PFS. Results: 59 early stage patients with triple negative breast cancer patients followed in Baskent University Hospital between 1997-2009 were enrolled into the study. The median age of patients was 49. Median follow-up duration was 27 months (0.27-132 months). Two patients died during the follow-up. Invasive ductal carcinoma pathology was reported in 38 patients, invasive lobular in 3 patients, medullary in 5 patients.Almost half of the patients had LVI. 79% of patients had a T2 disease. 30% of patients’ tumor histological grade was III. Cancer history in the family was present in 95% of patients. Almost half of the patients had stage II disease. Adjuvant chemotherapy was given to 43 patients. Relapses were observed in 15 patients.The most common metastatic site was lung. Patients having high grade tumor, &gt;3 (+) lymph nodes, younger age have higher chance of relapse during follow-up. Conclusions: In accordance with the literature, our triple negative breast cancer patients showed more aggressive characteristics. Although median follow-up is short, one-fourth of the patients having recurrence support natue of the triple negative breast cancer patients. In our study, triple negative patients had younger age at diagnosis, high grade tumors and more tendency to metastasize to visceral organs.
Simultaneous analysis of endogenous DNA adducts in chronic lymphocytic leukemia patients
Authors: Michaela Wirtz, Jochen Vom Brocke, Michael Podeschwa, David Oscier, Hans-Josef Altenbach, Siegmar Gäb, Oliver J. Schmitz
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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Oxidized bases represent DNA lesions induced by hydroxyl radicals, hydrogen peroxide, superoxide, peroxynitrite, singlet oxygen or one-electron oxidation reactions. A number of modified nucleosides, including diastereomeric forms, have been characterized in detailed model studies. Despite the abundance of DNA adducts resulting from oxidative damage, the analysis of these adducts is not always simple, because of the potential artifactual oxidation of the overwhelmingly larger concentrations of normal bases during sample preparation and analysis. The compound most commonly investigated in studies of oxidative stress is 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-HOdG), and, depending on the analytical method used, the literature reports quite widely varying amounts of this oxidative modification. By optimization of our previously published method we are now able not only to determine the genomic methylation level but also to quantitate various biomarkers of oxidative stress in a single analytical run. The method involves hydrolyzing DNA to modified and unmodified 2′-deoxynucleoside-3′-monophosphates, labeling the nucleotides with BODIPY® FL EDA as fluorescence marker, micellar electrokinetic chromatography and laser-induced-fluorescence detection (CE-LIF). It has been validated to a reproducible, high-throughput method which in epidemiological studies allows the quantification of adducts with low standard deviations. In the ongoing investigation presented here, we have so far analyzed N6-etheno-2’-deoxyadenosine-3′-monophosphate (etheno-dAMP), 2′-deoxyuridine-3′-monophosphate (dUMP), 2′-deoxyinosine-3′-monophosphate (dIMP), 5,6-dihydro-5,6-dihydroxy-2′-deoxy-thymidine-3′-monophosphate (dTgMP) and 5-methyl-2′-deoxycytidine-3′-monophosphate (5mdCMP) in DNA samples from CLL patients. The quantification of the first four was enabled by the addition of standards synthesized by members of our group. The strategy developed for synthesizing 2′-desoxynucleoside-3′-monophosphates will make it possible for us to prepare other DNA adducts, which could also be used as standards in 32P postlabeling.
Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017
Authors: M. Joannidis, W. Druml, L. G. Forni, A. B. J. Groeneveld, P. M. Honore, E. Hoste, M. Ostermann, H. M. Oudemans-van Straaten, M. Schetz
Journal: Intensive Care Medicine (2017)

Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity.
Shorter regimens for multidrug-resistant tuberculosis should also be applicable in Europe
Authors: Einar Heldal, Armand Van Deun, Chen-Yuan Chiang, Hans L. Rieder
Journal: European Respiratory Journal (2017)

Since May 2016, the World Health Organization (WHO) has recommended shorter regimens to treat rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB), substantially reducing the treatment duration to 9–12 months [1]. van der Werf et al. [2] estimated that only 11% of RR/MDR-TB patients in the European Union (EU)/European Economic Area (EEA) fulfilled the WHO inclusion criteria, which is similar to estimates by Lange et al. [3] and Sotgiu et al. [4]. This estimate raises concerns, as that the conventional long-duration regimen has very poor results in the EU/EEA. Health sector crisis, increasing inequality and xenophobia add to the urgency to prevent and manage MDR-TB. The main exclusion criteria are as follows. Shorter MDR-TB regimens should not be excluded because of resistance to first-line drugs or extrapulmonary sites <http://ow.ly/E4oo30bsIea>
Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.
Authors: Andreas Carus, Morten Ladekarl, Patricia Switten Nielsen, Henrik Hager, Bettina S Nedergaard, Torben Steiniche, Frede Donskov
Journal: Journal of Clinical Oncology (2013)

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b + neutrophils, CD163 + macrophages, and CD8 + lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b + neutrophils and CD163 + macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8 + lymphocytes , 0.85 for CD66b + neutrophils, and 0.92 for CD163 + macrophages (all p &lt;0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b + neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8 + lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163 + macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (&lt;0.019), II (0.02-0.05), III (0.06-0.24), and IV (&gt;0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b + neutrophil and low CD8 + lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b + neutrophil/CD8 + lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.
Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013–17: an epidemiological study of laboratory-confirmed case series
Authors: Xiling Wang, Hui Jiang, Peng Wu, Timothy M Uyeki, Luzhao Feng, Shengjie Lai, Lili Wang, Xiang Huo, Ke Xu, Enfu Chen, Xiaoxiao Wang, Jianfeng He, Min Kang, Renli Zhang, Jin Zhang, Jiabing Wu, Shixiong Hu, Hengjiao Zhang, Xiaoqing Liu, Weijie Fu, Jianming Ou, Shenggen Wu, Ying Qin, Zhijie Zhang, Yujing Shi, Juanjuan Zhang, Jean Artois, Vicky J Fang, Huachen Zhu, Yi Guan, Marius Gilbert, Peter W Horby, Gabriel M Leung, George F Gao, Benjamin J Cowling, Hongjie Yu
Journal: The Lancet Infectious Diseases (2017)
Standard operating procedures for tuberculosis care
Authors: Ivan Solovic, Ibrahim Abubakar, Giovanni Sotgiu, Masoud Dara, Delia Goletti, Raquel Duarte, Stefano Aliberti, Fernando Maria de Benedictis, Brian Ward, Vitor Teixeira, Christina Gratziou, Giovanni Battista Migliori
Journal: European Respiratory Journal (2017)

According to the World Health Organization (WHO), tuberculosis (TB) is the most important cause of mortality from infectious diseases, with 1.4 million deaths and 10.4 million cases of disease in 2015 [1]. Furthermore, the high global TB burden was compounded by an estimated 480 000 new cases of multidrug-resistant TB (MDR-TB) and 100 000 patients with rifampicin-resistant TB (RR-TB) – which are more difficult to treat – in 2015 [1]. In the WHO European Region, 36 970 deaths were reported, in association with over 320 000 TB incident cases [1, 2]. Recommendations to prioritise TB care, prevention and control, specifically among the most vulnerable populations <http://ow.ly/AhbC30bgzgz>
Abstract 12924: Morphological Mechanisms Underlying Efficacy of Paclitaxel-Coated Balloon Against Repeated In-Stent Restenosis
Authors: Suguru Nagamatsu, Kenichi Tsujita, Tatsuro Mitsuse, Takayoshi Yamashita, Yu Oimatsu, Masanobu Ishii, Noriaki Tabata, Takashi Miyazaki, Tomonori Akasaka, Daisuke Sueta, Tomokazu Ikemoto, Sunao Kojima, Koichi Kaikita, Seiji Hokimoto
Journal: Circulation (2016)

Background: In-stent restenosis (ISR) has been an important issue even after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Recently, paclitaxel-coated balloon (PCB) has emerged as a potential alternative to the conventional treatment of ISR (plain balloon angioplasty [PBA]) with lower incidence of re-ISR. However, detailed mechanisms underlying the clinical efficacy of PCB have been still unknown morphologically. Methods: Consecutive 32 patients whose in-stent restenotic lesions were treated by intravascular ultrasound (IVUS)-guided PBA (n=15) or PCB (n=17). Optical coherence tomography (OCT) and angiographic follow-up was done at 9 months after PCI for ISR, and the detailed IVUS/OCT and angiographic findings were compared to elucidate the differences in qualitative and quantitative characteristics of in-stent intima between the groups. Results: Compared with PBA group, re-ISR rate was significantly lower in PCB group (24% vs. 80%, p=0.005). Although post-PCI minimum lumen angiographic diameter (MLD) and IVUS area (MLA) were comparable between the groups (2.9±0.8mm vs. 2.8±0.8mm, p=0.7; 3.5±1.1mm 2 vs. 4.1±1.0mm 2 , p=0.9, respectively), MLD and MLA at follow-up were kept significantly larger in PCB group (2.7±0.9mm vs. 1.3±1.0mm, p=0.02; 4.3±2.8mm 2 vs. 2.1±0.9mm 2 , p=0.02, respectively), mainly attributable to smaller intimal area at MLA site (1.2±0.6mm 2 vs. 4.1±2.9mm 2 , p=0.03). Interestingly, post-PCB intima was significantly regressed in spite of the progression of post-PBA intima (-1.0±1.4mm 2 vs. 0.5±1.6mm 2 , p=0.01, Figure ). In terms of OCT-derived tissue characteristics of in-stent intima, post-PCB intima was more homogeneous rather than heterogeneous/layered (homogeneous/heterogeneous/layered: 60%/27%/13% vs. 18%/41%/41%, p=0.04). Conclusion: Clinical usefulness of PCB for DES-ISR might be based on not only smaller intimal area but also more stable intimal tissue of the regressed post-PCB intima.
Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis
Authors: Xiaoyun Guo, Haifeng Yin, Lei Li, Yi Chen, Jing Li, Jessica Doan, Rachel Steinmetz, Qinghang Liu
Journal: Circulation (2017)

Background: Programmed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. Methods: We examined the role of tumor necrosis factor receptor-associated factor 2 (Traf2) in regulating myocardial necroptosis and remodeling using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which Traf2 regulates necroptosis signaling. Results: We identified a critical role for Traf2 in myocardial survival and homeostasis by suppressing necroptosis. Cardiac-specific deletion of Traf2 in mice triggered necroptotic cardiac cell death, pathological remodeling, and heart failure. Plasma tumor necrosis factor α level was significantly elevated in Traf2 -deficient mice, and genetic ablation of TNFR1 largely abrogated pathological cardiac remodeling and dysfunction associated with Traf2 deletion. Mechanistically, Traf2 critically regulates receptor-interacting proteins 1 and 3 and mixed lineage kinase domain-like protein necroptotic signaling with the adaptor protein tumor necrosis factor receptor-associated protein with death domain as an upstream regulator and transforming growth factor β-activated kinase 1 as a downstream effector. It is important to note that genetic deletion of RIP3 largely rescued the cardiac phenotype triggered by Traf2 deletion, validating a critical role of necroptosis in regulating pathological remodeling and heart failure propensity. Conclusions: These results identify an important Traf2-mediated, NFκB-independent, prosurvival pathway in the heart by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure.
Antitumoral activity of the novel antitumoral compound CLU-502, isolated from Clusia rosea, in neuroblastoma and leukemia cell lines
Authors: David Diaz-Carballo, Ralf Axel Hilger, Sascha Malak, Dirk Strumberg, Siegfried Seeber
Journal: Cancer Research (2006)

2511   We have characterized a polyisoprenylated benzophenone isolated from  Clusia rosea , collected in Florida, USA. This novel substance, called CLU-502, was isolated from methanolic extracts of the plant using RP-HPLC coupled to a PDA-detector. In the SRB proliferation assay, CLU-502 demonstrated a potent cytotoxic activity in a panel of human tumor cell lines such as neuroblastoma and leukemia. Both, wild-type cell lines and sub-lines resistant to doxorubicin, cis-platin, etoposide or 5-fluorouracil were highly sensitive to CLU-502. Interestingly, normal fibroblasts were more resistant to this compound than cancer cells. CLU-502 inhibits the unwinding activity of topoisomerase I in a relaxation of pBR322l plasmid, as well as the decatenation of kinetoplasmids by human topoisomerase II. In addition, CLU-502 induce a dose-dependent inhibition of telomerase activity in vitro. A dose-dependent effect on the phosphorylation of ERK1/2, the cytosolic downstream enzymes of the MAP-kinase pathway, was also detected in Western blot analyses. The interaction of CLU-502 with PD98059, a specific inhibitor of ERK1/2 phosphorylation, resulted in a synergistic cytotoxic effect when both drugs were administered to tumor cells simultaneously. As the result of the exposure of cell cultures to CLU-502, a cell cycle arrest of the G 1  phase was detected. Finally, an apoptosis/DNA-damage in tumor cells was observed in agarose gels after the exposure of CLU-502 at different concentrations. CLU-502 inhibits Akt/PKB in NB cells. Initial toxicological studies in a nude mouse model revealed that treatment with CLU-502 was well tolerated up to 100 mg/kg. The antitumoral effect are currently analyzed in vivo in a neuroblastoma nude mouse model
C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
Authors: Meritxell Alberich-Jordà, Bas Wouters, Martin Balastik, Clara Shapiro-Koss, Hong Zhang, Annalisa Di Ruscio, Hanna S. Radomska, Alexander K. Ebralidze, Giovanni Amabile, Min Ye, Junyan Zhang, Irene Lowers, Roberto Avellino, Ari Melnick, Maria E. Figueroa, Peter J.M. Valk, Ruud Delwel, Daniel G. Tenen
Journal: Journal of Clinical Investigation (2013)
Blocking the Cycle: Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic, Hormone Receptor–Positive Breast Cancer
Authors: Seth A. Wander, Erica L. Mayer, Harold J. Burstein
Journal: Journal of Clinical Oncology (2017)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old postmenopausal woman was diagnosed with breast cancer 6 years ago when she presented with a stage II (T2N1), right-sided, invasive ductal carcinoma considered grade 2 of 3 on core biopsy, with a positive fine-needle aspiration of a palpable, ipsilateral axillary lymph node. Immunohistochemical analysis was positive for estrogen and progesterone receptor expression and negative for human epidermal growth factor receptor 2 (HER2) overexpression. She received neoadjuvant dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy, followed by breast-conserving surgery and axillary lymph node dissection, which revealed residual disease in three of 11 nodes. She received adjuvant radiation therapy and initiated letrozole, with excellent compliance during the interval 6-year period. While receiving adjuvant letrozole therapy, she reported 3 months of worsening back pain. Skeletal scintigraphy and cross-sectional imaging confirmed widespread osseous metastatic disease and right supraclavicular lymph node enlargement ( Fig 1 ). Core biopsy of the involved lymph node confirmed estrogen receptor (ER)–positive (90%), progesterone receptor–negative, HER2-negative recurrent metastatic breast cancer. The patient reported mild pain that was adequately controlled with over-the-counter anti-inflammatory medications. She has remained active with an excellent performance status.