tbuckley/cabot-search huggingface dataset:
Circadian rhythm and the influence of physical activity on circulating surfactant protein D in rheumatoid arthritis at different stages
Authors: SV Hoegh, Tine Lottenburger, GL Sørensen, Anne Friesgaard Christensen, I Tornøe, Kim Hørslev-Petersen, Uffe Holmskov, Peter Junker
Journal: Annals of the Rheumatic Diseases (2010)
Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice
Authors: Yuki Hirano, Alex Choi, Masashi Tsuruta, Jen Erh Jaw, Yeni Oh, David Ngan, Konosuke Moritani, Yu-Wei Roy Chen, Sheena Tam, Yuexin Li, Dragoş M. Vasilescu, James C. Hogg, Gordon Francis, Pascal Bernatchez, Shu-Fan Paul Man, Don D. Sin
Journal: Cardiovascular Research (2017)

Although surfactant protein-D (SP-D) is a pneumoprotein that is predominantly synthesized by type II epithelial cells in the lung, individuals with increased circulating levels of SP-D are at an elevated risk of mortality from ischemic heart disease. Whether SP-D contributes directly to atherosclerosis is unknown. We determined the effects of SP-D gene deletion in a mouse model of atherosclerosis.SP-D knockout (KO) mice were crossed with hyperlipidemic and atherosclerosis-prone apolipoprotein E (ApoE) KO mice to generate SP-D/ApoE double knockout (DKO) mice. Mice were placed on a high-fat diet for 12 weeks beginning at 8 weeks of age. Compared with ApoE KO mice, SP-D/ApoE DKO mice had significantly less atherosclerosis with reduced macrophage accumulation, decreased local macrophage proliferation, and increased smooth muscle cell coverage in plaques. Interestingly, SP-D deficiency worsened hypercholesterolemia and induced obesity and insulin resistance but suppressed plasma interleukin-6 (IL-6) levels. SP-D deficiency also reduced blood monocytes and neutrophils counts in ApoE KO mice.SP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality.
Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase
Authors: Ajay Gupta, David Thompson, Andrew Whitehouse, Tim Collier, Bjorn Dahlof, Neil Poulter, Rory Collins, Peter Sever
Journal: The Lancet (2017)
Long-Term Follow-Up of the Intergroup Exemestane Study
Authors: James P. Morden, Isabel Alvarez, Gianfilippo Bertelli, Alan S. Coates, Robert Coleman, Lesley Fallowfield, Jacek Jassem, Stephen Jones, Lucy Kilburn, Per E. Lønning, Olaf Ortmann, Claire Snowdon, Cornelis van de Velde, Jørn Andersen, Lucia Del Mastro, David Dodwell, Stig Holmberg, Hanna Nicholas, Robert Paridaens, Judith M. Bliss, R. Charles Coombes
Journal: Journal of Clinical Oncology (2017)

Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non–breast cancer–related deaths now reported, breast cancer–free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P &lt; .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, −0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, −0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality.
Ventilator-associated pneumonia: when is a pathogen not a pathogen?
Authors: Michael J Cox
Journal: Thorax (2017)

The context of respiratory microbiology is changing. 16S rRNA gene sequencing is a workhorse method in the field of environmental microbiology, established for over 30 years.1 Rather than requiring growth of organisms on agar plates it targets the DNA of all the microorganisms present, revealing bacteria irrespective of their particular growth requirements. Together with metagenomics, the untargeted shotgun sequencing of DNA extracted from a sample, these techniques have been applied to the respiratory tract. These approaches have revealed a characteristic respiratory community of microorganisms, a respiratory microbiota that varies in different diseases.2–6 The most prevalent organisms in the healthy respiratory tract are Streptococcus spp., Veillonella spp. and Prevotella spp.; the latter two genera being anaerobic bacteria, intolerant of oxygen and not commonly isolated by classic microbiology approaches.

At times studies that use these techniques might seem to be just describing long lists of bacterial names, but sampling over time reveals dynamic interactions between organisms and with their environment and the word ‘community’ is therefore used deliberately. Not all of these changes in the presence and abundance of these organisms are immediately explicable; they might relate to any one of an enormous number of variables not measured by clinical studies. Forced expiratory volume has very little direct impact on a microorganism in the respiratory tract, whereas the presence of a particular microbial nutrient will.

Molecular methods, such as 16S rRNA gene sequencing, have a different resolution to clinical culture. They are capable of sensitively detecting bacteria without the narrow selection of the limited range of culture conditions commonly used. Conversely, they are not always capable of providing identification beyond the level of genus. Where microbiota analyses really excel is in providing a …
Brentuximab Vedotin Plus ESHAP (BRESHAP) Is a Highly Effective Combination for Inducing Remission in Refractory and Relapsed Hodgkin Lymphoma Patients Prior to Autologous Stem Cell Transplant: A Trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO)
Authors: Ramon Garcia-Sanz, Anna Sureda, Ana Pilar Gonzalez, Fatima De la Cruz, Blanca Sanchez-Gonzalez, Antonia Rodriguez, Eva Domingo-Domenech, Moreno Miriam, Moreno Miriam, Javier Lopez, Piñana Luis Jose, Gabriela Rodríguez, Miguel Canales, Antonio Gutierrez, Maria Dolores Caballero, Carmen Martinez
Journal: Blood (2016)
Identification of differentially expressed genes in a metastatic variant of an orthotopic model of bladder cancer
Authors: Sonya M. King, Heiko Peters, Barry R. Davies
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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At presentation 25-30% of human bladder tumours are classified as muscle–infiltrative, which by definition have already demonstrated the ability to invade & metastasise. Patients with these tumours have a significantly reduced 5-year survival rate, which often correlates with the development of metastatic disease following failure of treatment such as surgery or radiotherapy. Since metastasis is a multi-step process, in which the tumour cell must overcome many obstacles, it is likely that it involves the de-regulation of many genes. This complexity, combined with limitations of current animal models, means that bladder cancer metastasis is poorly understood. In an effort to further understand the metastatic process, we have established a metastatic variant of a non-metastatic rat bladder cell line. This was achieved by serial orthotopic implantation of the non-metastatic line into the bladder wall of immunocompetant animals. We have compared gene expression between the non-metastatic parent line and the metastatic variant using the Affymetrix rat 230A microarray. The results demonstrated that a total of 248 gene sequences differed by a factor of 2.5 or more between the two cell lines. Of these 248 sequences, 104 were known genes, with 55 being down-regulated in the metastatic cell line compared with the parental line and 49 being up-regulated. Furthermore, 33 of the 55 down-regulated known genes were absent altogether from the metastatic variant, while 22 of the 49 up-regulated known genes were present in the metastatic variant but absent from the parental line. Three classes of gene were strikingly well represented in the panel of differentially expressed genes; these encode proteins involved in (1) proteolysis (e.g. MMP3, MMP10, Cathepsin Y, cystatin N, TIMP3), (2) adhesion or cell-cell communication (e.g. connexins 30 and 40, various integrins) and (3) composition or stability of the extracellular matrix (e.g. fibronectin, decorin, lysyl oxidase, fibulin 3). Expression of candidate genes identified by the microarray experiment has been verified by RT-PCR and western blotting analysis; the pattern of differential protein expression is consistent with that of their mRNAs in the two variants. This model system may be suitable for identifying genes potentially involved in metastasis of bladder cancer and suggest novel targets for therapeutic intervention.
Abstract 17470: NF-{kappa}B Activation Down Stream of Tuber Sclerosis Complex -mTOR Signaling pathway is Suppressed in Doxorubicin-Induced Cardiotoxicity
Authors: Rimpy Dhingra, Joseph W Gordon, Hongying Gang, Lorrie A Kirshenbaum
Journal: Circulation (2011)

The signaling networks that coordinate cell survival and cell death are poorly defined in the heart. The mammalian target of rapamycin (mTOR) is a highly conserved serine threonine kinase centrally...
RS1008805 polymorphism in CYP19A1 gene in relation to the efficacy of hormone therapy in early breast cancer.
Authors: Xiaojia Wang, Xiying Shao, Yabing Zheng, Lei Shi, Dehong Zou
Journal: Journal of Clinical Oncology (2015)

e11568 Background: It has been suggested that genetic polymorphisms in CYP19A1 gene were related to aromatase activity as well as circulating steroid hormone levels in postmenopausal women. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with clinical outcome for hormone therapy. Methods: Genotyping for CYP19A1 polymorphism rs1008805 was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Results: Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS, 5-year DFS rate. However, in postmenopausal women, rs1008805 genotypes were significantly associated with DFS and 5-years DFS rate (AA versus AG versus GG: 89.2 months versus 58.2 versus 32.7 months; 55.9% versus 47.8% versus 0%; P = 0.019). In addition, when the population was subgrouped into two cohorts, women carrying GG variant have a poorer DFS, 5-years DFS rate (GG versus AA or AG: 32.7 months versus 70.6 months; 0% versus 52.1%; HR, 3.613; 95% CI,1.380-9.457; P = 0.005). Furthermore, being adjusted by patients features in multivariate analyses, GG genotype remained an independent prognostic factor for DFS (HR, 3.439; 95% CI, 1.251-9.456; P = 0.017). However, there was no significant differences in DFS and 5-years DFS rate between women harbor the minor allele and those with the homozygous common allele (AG or GG versus AA: 52.4 months versus 89.2 months; 41.0% versus 52.9%; HR, 1.288; 95% CI, 0.705-2.353; P = 0.408). In addition, there were no differences between rs1008805 polymorphisms and DFS among premenopausal women. Conclusions: The homozygous minor allele (GG) of CYP19A1 rs1008805 is significantly associated with worse clinical outcome of hormone therapy in postmenopausal HR-positive early breast cancer patients. If confirmed, genotyping for CYP19A1 polymorphism rs1008805 may provide predictive information for better selection of endocrine treatment.
Epoetin biosimilars in the management of chemotherapy-induced anemia in elderly patients: A subanalysis of the ORHEO study.
Authors: Jean-Emmanuel Kurtz, Pierre-Louis Soubeyran, Mauricette Michallet, Elisabeth Luporsi-Gely
Journal: Journal of Clinical Oncology (2013)

e20513 Background: Chemotherapy-induced anemia (CIA) treatment requires transfusion, or epoietin administration. Elderly patients (pts) may experience severe complications from CIA, with fatigue and cardiovascular events. Methods: ORHEO (place of biOsimilaRs in the therapeutic management of anemia secondary to chemotherapy in HaEmatology and Oncology) was a post-marketing, observational, prospective, multicentric study. Adult CIA (Hb&lt;110g/l) pts with solid tumors, lymphomas or myelomas and eligible for epoetin alpha biosimilar (EAB) treatment were included to receive EAB according to drugs approval recommendations. Recorded data included demographics, performance status, blood count and iron load profile. Safety (NCI-CTC V2.0) and efficacy were also assessed. The primary study endpoint was the rate of responders (defined as increase in Hb levels to 100 g/l or at least 10 g/l since inclusion visit, or reaching target Hb set at start of study, without any blood transfusions in the 3 weeks prior to measurement) at +3 months (M+3). Other endpoints included safety, patterns of treatment interruption and rate of responders at +6 months (M+6). Here we present data for the elderly (&gt;= 70 years old) pts. Results: 1,009 pts (54.3% male, 45.7% female) &gt;= 70 y.o. were included in this analysis. Median age was 77 y, range [70-93]. At baseline, 36.3, 57.8 and 3.4% of pts had respectively grade 1, 2 and 3 anemia. Iron supplementation was given in 9.9 (oral) and 16.0% (IV) of pts. At M+3, 84.0% of pts were responders (IC95% 81.4-86.3). Moreover, respectively 241 pts (23.8%) and 139 pts (13.7%) had stopped EAB permanently or temporarily, mainly because of efficacy (45.2 and 79.1% respectively); other reasons were side-effects (2.9 and 0.7% respectively), lack of efficacy (7.0 and 4.3%), and unspecified reason (44.8 and 15.8%). Similar results were observed at M+6 with 86.8% of responders. 17.0% of pts reported side effects (all grades); the most frequent were thromboembolic events (4.5%). No EAB-related death was reported. 94.6% of pts reported being satisfied with EAB therapy at M+3 and M+6 and willing to restart if needed. Conclusions: EAB therapy is efficacious on CIA management in elderly pts with low toxicity.
A “tandem approach” using sequential diagnostic (ultraslim) and therapeutic (standard size) direct freehand cholangioscopy to guide mechanical lithotripsy of a giant cystic duct remnant stone
Authors: Vincent Zimmer, Frank Lammert
Journal: Endoscopy (2017)

This is the case of an 85-year-old woman with a distant history of cholecystectomy and complicated bile duct stone disease who had undergone several endoscopic retrograde cholangiography (ERC) procedures including standard-incision papillotomy elsewhere, and was now undergoing repeat ERC after resolution of an episode of acute cholangitis. Because of a complicated ERC anatomy, fluoroscopy provided limited information as to the location of the stone; basket capture was unsuccessful ([Fig. 1]).
The Synergistic Effect of Melphalan and XPO1 Inhibition in Pre-Clinical Models of Multiple Myeloma
Authors: Yan Cui, Joel G Turner, Jana L Dawson, Juan A Gomez, Kenneth H. Shain, Mark B Meads, Erkan Baloglu, William S. Dalton, Taiga Nishihori, Daniel M Sullivan
Journal: Blood (2016)
Quality of Patient Decisions About Breast Reconstruction After Mastectomy
Authors: Clara Nan-hi Lee, Allison M. Deal, Ruth Huh, Peter Anthony Ubel, Yuen-Jong Liu, Lillian Blizard, Caprice Hunt, Michael Patrick Pignone
Journal: JAMA Surgery (2017)

Breast reconstruction has the potential to improve a person's body image and quality of life but has important risks. Variations in who undergoes breast reconstruction have led to questions about the quality of patient decisions.To assess the quality of patient decisions about breast reconstruction.A prospective, cross-sectional survey study was conducted from June 27, 2012, to February 28, 2014, at a single, academic, multidisciplinary oncology clinic among women planning to undergo mastectomy for stage I to III invasive ductal or lobular breast cancer, ductal carcinoma in situ, or prophylaxis.Mastectomy only and mastectomy with reconstruction.Knowledge, as ascertained using the Decision Quality Instrument; preference concordance, based on rating and ranking of key attributes; and decision quality, defined as having knowledge of 50% or more and preference concordance.During the 20-month period, 214 patients were eligible, 182 were approached, and 32 missed. We enrolled 145 patients (79.7% enrollment rate), and received surveys from 131 patients (72.0% participation rate). Five participants became ineligible. The final study population was 126 patients. Among the 126 women in the study (mean [SD] age, 53.2 [12.1] years), the mean (SD) knowledge score was 58.5% (16.2%) and did not differ by treatment group (mastectomy only, 55.2% [15.0%]; mastectomy with reconstruction, 60.5% [16.5%]). A total of 82 of 123 participants (66.7%) had a calculated treatment preference of mastectomy only; 39 of these women (47.6%) underwent mastectomy only. A total of 41 participants (32.5%) had a calculated treatment preference of mastectomy with reconstruction; 36 of these women (87.8%) underwent mastectomy with reconstruction. Overall, 52 of 120 participants (43.3%) made a high-quality decision. In multivariable analysis, white race/ethnicity (odds ratio [OR], 2.72; 95% CI, 1.00-7.38; P = .05), having private insurance (OR, 1.61; 95% CI, 1.35-1.93; P < .001), having a high school education or less (vs some college) (OR, 4.84; 95% CI, 1.22-19.21; P = .02), having a college degree (vs some college) (OR, 1.95; 95% CI, 1.53-2.49; P < .001), and not having a malignant neoplasm (eg, BRCA carriers) (OR, 3.13; 95% CI, 1.25-7.85; P = .01) were independently associated with making a high-quality decision.A minority of patients undergoing mastectomy in a single academic center made a high-quality decision about reconstruction. Shared decision making is needed to support decisions about breast reconstruction.
Somatic Mutations in Schinzel-Giedion Syndrome Gene SETBP1 Determine Progression in Myeloid Malignancies
Authors: Hideki Makishima, Kenichi Yoshida, Nhu Nguyen, Masashi Sanada, Yusuke Okuno, Kwok Peng Ng, Bartlomiej P Przychodzen, Kristbjorn O Gudmundsson, Bandana A Vishwakarma, Andres Jerez, Ines Gomez-Segui, Mariko Takahashi, Yuichi Shiraishi, Yasunobu Nagata, Kathryn M Guinta, Hiraku Mori, Mikkael A. Sekeres, Kenichi Chiba, Hideki Muramatsu, Hirotoshi Sakaguchi, Ronald Paquette, Michael A McDevitt, Seiji Kojima, Yogen Saunthararajah, Satoru Miyano, Lee-Yung Shih, Yang Du, Seishi Ogawa, Jaroslaw P. Maciejewski
Journal: Blood (2012)
Surgical resection versus watchful waiting in low-grade gliomas
Authors: A.S. Jakola, A.J. Skjulsvik, K.S. Myrmel, K. Sjåvik, G. Unsgård, S.H. Torp, K. Aaberg, T. Berg, H.Y. Dai, K. Johnsen, R. Kloster, O. Solheim
Journal: Annals of Oncology (2017)

Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers.Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival.A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5-7.2) in region A compared with 14.4 years (95% CI 10.4-18.5) in region B (P < 0.01). The effect of surgical strategy remained after adjustment for molecular markers (P = 0.001).In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.