tbuckley/cabot-search huggingface dataset:
Exercise prescription for people with osteoporotic vertebral fracture
Authors: Richard Kasch, Harry Merk, Rafael Z Pinto
Journal: British Journal of Sports Medicine (2013)

Osteoporotic vertebral fracture is a common type of fracture in people with osteoporosis and has been associated with a reduced quality of life1 and a higher risk of subsequent vertebral fracture.2 Exercise intervention is often recommended as part of the multimodal approach for the management of osteoporosis. It is unclear whether exercise intervention has benefits among people with osteoporotic vertebral fractures.

To evaluate the benefits and harms of exercise interventions on the incidence of future fractures and adverse events among adults with a history of osteoporotic vertebral fracture compared with non-exercise/non-active physical therapy intervention, no intervention or placebo. As a secondary objective of this review, the authors examined the effects of exercise on nine different clinical and physiological measures.

Six electronic databases ( The Cochrane Library , MEDLINE, EMBASE, CINAHL, AMED and PEDro) were searched for randomised controlled trials or quasi-randomised trials published in any language up until November 2011. The authors aimed to locate ongoing or recently completed trials and conference proceedings by …
Abstract 4029: Enhanced chemosensitivity of estrogen receptor-α (ERα)-negative breast cancer through soybean genistein-induced epigenetic reactivation of <i>ERα</i>
Authors: Yuanyuan Li, Trygve Tollefsbol
Journal: Cancer Research (2012)

Abstract Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and has a poor prognosis due to the lack of estrogen target-directed therapies. The soybean isoflavone, genistein (GE), has been shown to prevent and inhibit breast cancer and recent studies have suggested that GE can enhance the anticancer capacity of an estrogen antagonist, tamoxifen (TAM), especially in ERα-positive breast cancer cells. However, the role of GE in ERα-negative breast cancer remains unknown. In our current studies, we found that GE can reactivate ERα expression and this effect was synergistically enhanced when combined with a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), in ERα-negative MDA-MB-231 breast cancer cells. GE treatment also re-sensitized ERα-dependent cellular responses to activator 17β-estradiol (E2) and antagonist TAM. Further studies revealed that GE can lead to remodeling of the chromatin structure in the ERα promoter thereby contributing to ERα reactivation. The global enzymatic activities for HDACs and DNA methyltransferases (DNMTs) mediated by GE were altered to favor ERα up-regulation. Consistently, dietary GE significantly reduced the growth of ERα-negative mouse xenograft tumors due at least in part to ERα reactivation. The combination of GE with TAM had more prominent effects on delaying tumor growth than either treatment alone. Collectively, our studies suggest that soybean genistein can epigenetically restore ERα expression, which in turn increases TAM-dependent anti-estrogen chemosensitivity. The results from our studies revealed a novel chemotherapeutic combination approach using bioactive soybean product and anti-hormone therapy in refractory ERα-negative breast cancer which will provide more effective options in breast cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4029. doi:1538-7445.AM2012-4029
Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece)
Authors: H.C. Maltezou, P. Giakkoupi, A. Maragos, M. Bolikas, V. Raftopoulos, H. Papahatzaki, G. Vrouhos, V. Liakou, A.C. Vatopoulos
Journal: Journal of Infection (2009)
Recurrent bronchopulmonary infections in the left lung of a 21-month-old female
Authors: G. Bava, O. Sacco, E. Bava, I. Borini, F. Pesce, P. Tomà, G. A. Rossi
Journal: European Respiratory Journal (2006)

A 21-month-old female with a history of failure to thrive after the age of 6 months and recurrent, slowly resolving bronchopulmonary infections involving the left lung and leading to respiratory distress requiring oxygen administration, was referred to the Giannina Gaslini Institute (Genova, Italy) for further evaluation.On admission, in December 2004, the patient was in mediocre general conditions.Her height and weight were 56 cm and 10.0 kg (both 25 th percentile), respectively.Her respiratory rate was 33 breaths?min -1 .Physical examination demonstrated decreased percussion and auscultatory sounds over the left hemithorax.Screening on immunological disorders revealed that B-and T-cell functions were normal.Sweat test and cystic fibrosis transmembrane regulator gene mutations were negative.Results of the blood and microbiological tests performed on admission are shown in table 1.
Role of the Tumor Suppressor RASSF1A in Mst1-Mediated Apoptosis
Authors: Hyun Jung Oh, Kyung-Kwon Lee, Su Jung Song, Mi Sun Jin, Min Sup Song, Joo Hyun Lee, Chang Rak Im, Jie-Oh Lee, Shin Yonehara, Dae-Sik Lim
Journal: Cancer Research (2006)

Mammalian sterile 20-like kinase 1 (Mst1) is activated by both caspase-mediated cleavage and phosphorylation in response to apoptotic stimuli, including Fas ligation. Here, we examined the possible role of the tumor suppressor RASSF1A in Mst1 activation and Mst1-mediated apoptosis induced by death receptor signaling. Immunoprecipitation and immunofluorescence analyses revealed that Mst1 was associated with RASSF1A in cultured mammalian cells, with both proteins colocalizing to microtubules throughout the cell cycle. Whereas purified recombinant RASSF1A inhibited the kinase activity of purified recombinant Mst1 in vitro, overexpression of RASSF1A increased the kinase activity of Mst1 in intact cells, suggesting that regulation of Mst1 by RASSF1A in vivo involves more than the simple association of the two proteins. Both the activation of Mst1 and the incidence of apoptosis induced by Fas ligation were markedly reduced in cells depleted of RASSF1A by RNA interference and were increased by restoration of RASSF1A expression in RASSF1A-deficient cells. Moreover, the stimulatory effect of RASSF1A overexpression on Fas-induced apoptosis was inhibited by depletion of Mst1. These findings indicate that RASSF1A facilitates Mst1 activation and thereby promotes apoptosis induced by death receptor signaling.
Analyses of RNA Polymerase II Genes from Free-Living Protists: Phylogeny, Long Branch Attraction, and the Eukaryotic Big Bang
Authors: Joel B. Dacks, Alexandra Marinets, W. Ford Doolittle, Thomas Cavalier-Smith, John M. Logsdon
Journal: Molecular Biology and Evolution (2002)

The phylogenetic relationships among major eukaryotic protist lineages are largely uncertain. Two significant obstacles in reconstructing eukaryotic phylogeny are long-branch attraction (LBA) effects and poor taxon sampling of free-living protists. We have obtained and analyzed gene sequences encoding the largest subunit of RNA Polymerase II (RPB1) from Naegleria gruberi (a heterolobosean), Cercomonas ATCC 50319 (a cercozoan), and Ochromonas danica (a heterokont); we have also analyzed the RPB1 gene from the nucleomorph (nm) genome of Guillardia theta (a cryptomonad). Using a variety of phylogenetic methods our analysis shows that RPB1s from Giardia intestinalis and Trichomonas vaginalis are probably subject to intense LBA effects. Thus, the deep branching of these taxa on RPB1 trees is questionable and should not be interpreted as evidence favoring their early divergence. Similar effects are discernable, to a lesser extent, with the Mastigamoeba invertens RPB1 sequence. Upon removal of the outgroup and these problematic sequences, analyses of the remaining RPB1s indicate some resolution among major eukaryotic groups. The most robustly supported higher-level clades are the opisthokonts (animals plus fungi) and the red algae plus the cryptomonad nm—the latter result gives added support to the red algal origin of cryptomonad chloroplasts. Clades comprising Dictyostelium discoideum plus Acanthamoeba castellanii (Amoebozoa) and Ochromonas plus Plasmodium falciparum (chromalveolates) are consistently observed and moderately supported. The clades supported by our RPB1 analyses are congruent with other data, suggesting that bona fide phylogenetic relationships are being resolved. Thus, the RPB1 gene has apparently retained some phylogenetically meaningful signal, making it worthwhile to obtain sequences from more diverse protist taxa. Additional RPB1 data, especially in combination with other genes, should provide further resolution of branching orders among protist groups within the apparently rapid early divergence of eukaryotes.
No health safety net for failed asylum seekers and others in UK
Authors: Karen A McColl
Journal: BMJ (2006)

EDITOR—Hall shows that current health rules, which deny some of the most vulnerable people in the United Kingdom essential medical care, flout international law.1 2 Evidence is mounting of the impact the tougher restrictions on NHS entitlement are having on vulnerable migrants living in the UK.

Last month the Refugee Council published a report documenting 37 case studies of failed asylum seekers who were refused medical care that they needed.3 Medecins du Monde UK …
Targeted estrogen delivery reverses the metabolic syndrome
Authors: Brian Finan, Bin Yang, Nickki Ottaway, Kerstin Stemmer, Timo D Müller, Chun-Xia Yi, Kirk Habegger, Sonja C Schriever, Cristina García-Cáceres, Dhiraj G Kabra, Jazzminn Hembree, Jenna Holland, Christine Raver, Randy J Seeley, Wolfgang Hans, Martin Irmler, Johannes Beckers, Martin Hrabě de Angelis, Joseph P Tiano, Franck Mauvais-Jarvis, Diego Perez-Tilve, Paul Pfluger, Lianshan Zhang, Vasily Gelfanov, Richard D DiMarchi, Matthias H Tschöp
Journal: Nature Medicine (2012)
Direct Reprogramming for Cardiac Regeneration
Authors: Benoit G. Bruneau
Journal: Circulation Research (2012)

D irect reprogramming of endogenous fibroblasts into functional cardiomyocytes to regenerate the heart after myocardial infarction (MI) has long been a dream.A few years ago, this would have been considered by most to be science fiction.Certainly, the most optimistic scientists would probably categorize this as "highly unlikely to ever work."And yet, 2 papers, 1,2 including one in this issue of Circulation Research, 2 have achieved this, using two distinct approaches.These landmark studies will hopefully pave the way for effective approaches to restoring cardiac function after cardiac injury.
Long-term efficacy of motivational interviewing on improving continuous positive airway pressure adherence in obstructive sleep apnea: A randomized controlled trial
Authors: Agnes Lai, Jamie Lam, Daniel Fong, Mary Ip
Journal: European Respiratory Journal (2013)

Introduction: Long term adherence to continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea (OSA) subjects is important to alleviate symptoms and prevent health-related consequences.   Objectives: This study aimed to examine the long-term efficacy of a theory-based behavioral education (BMI-E) programme on improving CPAP adherence. We hypothesized that the application of BMI-E at the initial phase of using CPAP would enhance CPAP adherence in the long term.   Methods: Newly diagnosed OSA subjects were randomized into either standard education (SE) or BMI-E. SE group received general advice on CPAP use and BMI-E group received SE with an additional education session and a phone follow up. BMI-E programme consisted of theory-based education with brief motivational interviewing and negative-message framing. Primary outcome was to assess CPAP adherence 1 year after receiving BMI-E programme. Improvement in daytime sleepiness as assessed by Epworth Sleepiness Score (ESS) was secondary outcome.   Results: 100 subjects ranged from mild to severe OSA, were recruited with a mean±SD age of 52±10 years and ESS of 9±5. At 1 year, the proportion of subjects using CPAP were 84% verse 49% (p   Conclusions: Subjects receiving BMI-E were more likely to continue to use CPAP with better adherence and greater improvement in daytime sleepiness even after 1 year receiving BMI-E.
Henoch–Schönlein purpura (HSP) during treatment with anastrozole
Authors: M. Conti-Beltraminelli, O. Pagani, G. Ballerini, A. Richetti, R. Graffeo, M. Ruggeri, V. Forni, S. Pianca, C. Schönholzer, C. Mainetti, F. Cavalli, A. Goldhirsch
Journal: Annals of Oncology (2006)
Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide
Authors: Martin Glas, Caroline Happold, Johannes Rieger, Dorothee Wiewrodt, Oliver Bähr, Joachim P. Steinbach, Wolfgang Wick, Rolf-Dieter Kortmann, Guido Reifenberger, Michael Weller, Ulrich Herrlinger
Journal: Journal of Clinical Oncology (2009)

To evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy.Thirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard-dose CCNU, 100 mg/m2 on day 1 and TMZ 100 mg/m(2)/d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m(2) on day 1 and TMZ 150 mg/m(2) on days 2 to 6) for up to six courses.In the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O(6)-methylguanine-DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%).The combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.
Clonal Analysis Reveals a Common Progenitor for Endothelial, Myeloid, and Lymphoid Precursors in Umbilical Cord Blood
Authors: Aline Lisie Ramos, Radbod Darabi, Nasrin Akbarloo, Luciene Borges, Jacquelyn Catanese, Sean P. Dineen, Rolf A. Brekken, Rita C.R. Perlingeiro
Journal: Circulation Research (2010)

several studies demonstrate that hematopoietic tissues are a source of endothelial progenitor cells, which contribute to newly formed blood vessels during tissue repair in adults. However, it is not clear which cell type in these hematopoietic tissues gives rise to endothelial progenitor cells.to identity the origin of endothelial progenitors within the hematopoietic hierarchy and to assess their in vivo revascularization potential.using a single-cell sorting approach and in vitro multilineage differentiation assays, here we show that individual CD34(+)CD45(+)CD133(+)CD38(+) cells from cord blood uniquely have the ability to differentiate into T- and B-lymphoid, myeloid, and endothelial cells. The latter were characterized by the expression of VE-cadherin, KDR, von Willebrand factor, endothelial nitric oxide synthase, the lack of CD45, CD133, and c-fms (colony stimulating factor-1 receptor). Unexpectedly when transplanted into hindlimb ischemic NOD-scid IL2Rγ(null) mice, freshly isolated CD34(+)CD45(+)CD133(+)CD38(+) cells maintained their hematopoietic identity and were rarely found to integrate into host blood vessels. Nevertheless, they significantly improved perfusion, most likely through a paracrine mechanism. On the other hand, CD34(+)CD45(+)CD133(+)CD38(+) cells differentiated in vitro into endothelial cells were able to form vessels in vivo in both Matrigel plug and hindlimb ischemia transplantation assays.these findings indicate that the CD34(+)CD45(+)CD133(+)CD38(+) cell fraction contains a common progenitor for the hematopoietic and vascular lineages and may represent a valuable cell source for therapeutic applications.
Protein Expression of a Triad of Frequently Methylated Genes, <i>p73</i>, <i>p57<sup>Kip2</sup></i>, and <i>p15</i>, Has Prognostic Value in Adult Acute Lymphocytic Leukemia Independently of Its Methylation Status
Authors: Carlos Bueso-Ramos, Yunling Xu, Timothy J. McDonnell, Shawn Brisbay, Sherry Pierce, Hagop Kantarjian, Gary Rosner, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2005)

To study the relationship between protein expression and DNA methylation of a triad of cell-cycle regulatory genes known to be frequently methylated in adult acute lymphocytic leukemia (ALL).Protein expression of p73, p15, and p57Kip2 was analyzed by immunohistochemistry using a tissue microarray (TMA) platform. The TMA was constructed using pretreatment bone marrow biopsy specimens from 64 adult patients with ALL. Protein expression was then correlated with DNA methylation and relevant clinical biologic characteristics.p73 protein expression was observed in 19 (30%) patients, cytoplasmic p15 in 19 (31%), and p57 in 40 (70%). Three patients (5%) had expression of all three proteins, 16 (29%) of two proteins, 31 (55%) of one protein, and six (11%) of zero proteins. An inverse association was observed between p73 DNA methylation and protein expression (P = .003). This effect was not observed for either p15 or p57Kip2. Expression of any of the proteins studied was not associated with any distinct biologic characteristic. By multivariate analysis, expression of p57Kip2, cytoplasmic p15, or a combination of p57Kip2 with either p15 or p73 was associated with a better overall survival (P < .001, .04, and .03 respectively).Expression of a triad of cell cycle regulatory proteins that includes p73, p15, and p57Kip2 has prognostic value in adult patients with ALL independently of the methylation status of each gene.
Universal Poor Survival in Children With Medulloblastoma Harboring Somatic <i>TP53</i> Mutations
Authors: Uri Tabori, Berivan Baskin, Mary Shago, Noa Alon, Michael D. Taylor, Peter N. Ray, Eric Bouffet, David Malkin, Cynthia Hawkins
Journal: Journal of Clinical Oncology (2010)

Medulloblastoma is the prototype of treatment success in modern pediatric neuro-oncology. Unfortunately, 20% to 30% of tumors recur despite maximal resection and multimodal therapy. Multiple biologic prognostic markers have been investigated to predict recurrences, but controversy remains regarding their clinical utility. Because p53 immunopositivity is an adverse prognostic marker in pediatric medulloblastoma and TP53 mutations are associated with chemotherapy and radiation therapy resistance, we aimed to determine the extent and role of TP53 mutations in pediatric medulloblastoma treatment failure.One hundred eight of 111 consecutive patients diagnosed with medulloblastoma in our institution from 1995 to 2007 were included. Median follow-up time was 5.3 years in survivors. All samples were immunostained for p53 and erbB-2. Histologic grade and immunostaining were scored by two blinded reviewers. For 49 patients, frozen material was available for TP53 sequencing. The main outcome measures were overall and progression-free survival.Sixteen percent of sequenced medulloblastomas harbored a TP53 mutation. As a screening test, p53 immunohistochemistry was 100% sensitive and 83% specific for a TP53 mutation. Strikingly, all mutated tumors recurred early, and 5-year survival for average-risk patients was 0% for TP53-mutated medulloblastoma compared with 74% +/- 8% for wild-type medulloblastoma (P < .0001). Furthermore, 75% of recurrences in average-risk patients were associated with TP53 mutations. On multivariate analysis, TP53 mutation status was the strongest adverse prognostic factor (hazard ratio = 10.4, P = .003).Lack of long-term survival in TP53-mutated medulloblastomas highlights the role of TP53 mutations in medulloblastoma resistance to conventional therapies and the need for alternative treatments, and prospective validation of these findings is needed.
Disulfiram Treatment Facilitates Phosphoinositide 3-Kinase Inhibition in Human Breast Cancer Cells <i>In vitro</i> and <i>In vivo</i>
Authors: Haijun Zhang, Di Chen, Jonathan Ringler, Wei Chen, Qiuzhi Cindy Cui, Stephen P. Ethier, Q. Ping Dou, Guojun Wu
Journal: Cancer Research (2010)

Frequent genetic alterations of the components in the phosphoinositide 3-kinase (PI3K)/PTEN/AKT signaling pathway contribute greatly to breast cancer initiation and progression, which makes targeting this signaling pathway a promising therapeutic strategy for breast cancer treatment. In this study, we showed that in the presence of copper (Cu), disulfiram (DSF), a clinically used antialcoholism drug, could potently inhibit breast cancer cell growth regardless of the PIK3CA status. Surprisingly, the treatment with a mixture of DSF and copper (DSF-Cu) led to the decreased expression of PTEN protein and the activation of AKT in a dose- and time-dependent manner in different cell lines with or without PIK3CA mutations. Treatment of breast cancer cell lines with a combination of DSF-Cu and LY294002, a pan-PI3K inhibitor, resulted in the significant inhibition of cell growth when compared with either drug alone. In addition, the combined treatment of DSF and LY294002 significantly inhibited the growth of the breast tumor xenograft in nude mice induced by MDA-MB-231 cells expressing mutant PIK3CA-H1047R and PIK3CA-E545K, whereas neither DSF nor LY294002 alone could significantly retard tumor growth. Finally, the observed in vivo inhibitory effects are found associated with aberrant signaling alterations and apoptosis-inducing activities in tumor samples. Thus, our finding shows for the first time that treatment of breast cancer with DSF results in a novel feedback mechanism that activates AKT signaling. Our study also suggests that the combination of DSF and a PI3K inhibitor may offer a new combinational treatment model for breast cancer, particularly for those with PIK3CA mutations.
Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel
Authors: Carlos M. Galmarini, Isabelle Treilleux, Fatima Cardoso, Chantal Bernard-Marty, Virginie Durbecq, David Gancberg, Marie-Christine Bissery, Marianne Paesmans, Denis Larsimont, Martine J. Piccart, Angelo Di Leo, Charles Dumontet
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the role of microtubule-associated variables as potential predictors of response and clinical outcome in patients with advanced breast cancer receiving single-agent docetaxel or doxorubicin chemotherapy. Experimental Design: The analysis was done on 173 tumor samples from patients with locally advanced or metastatic breast cancer who have participated in the TAX-303 phase III trial in which patients were randomly assigned to receive docetaxel or doxorubicin. Expression of total α- and β-tubulin, classes II to IV β-tubulin isotypes, and τ protein was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded tumors from the primary breast cancer. Results: We observed that patients with “high” expression of class III β-tubulin isotype had a higher probability of response to docetaxel than to doxorubicin treatment (odds ratio, 1.9; 95% confidence interval, 1.01-3.7; P = 0.05). No difference was observed in terms of time to progression or in terms of overall survival. Conclusions: This study suggests that the superiority of docetaxel over doxorubicin seems to be confined to the subgroup of patients with “high” expression of class III β-tubulin isotype.