tbuckley/cabot-search huggingface dataset:
CKD Prevalence Varies across the European General Population
Authors: Katharina Brück, Vianda S. Stel, Giovanni Gambaro, Stein Hallan, Henry Völzke, Johan Ärnlöv, Mika Kastarinen, Idris Guessous, José Vinhas, Bénédicte Stengel, Hermann Brenner, Jerzy Chudek, Solfrid Romundstad, Charles Tomson, Alfonso Otero Gonzalez, Aminu K. Bello, Jean Ferrieres, Luigi Palmieri, Gemma Browne, Vincenzo Capuano, Wim Van Biesen, Carmine Zoccali, Ron Gansevoort, Gerjan Navis, Dietrich Rothenbacher, Pietro Manuel Ferraro, Dorothea Nitsch, Christoph Wanner, Kitty J. Jager
Journal: Journal of the American Society of Nephrology (2015)

CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1–5 was defined as eGFR&lt;60 ml/min per 1.73 m 2 , as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria &gt;30 mg/g, and CKD stages 3–5 was defined as eGFR&lt;60 ml/min per 1.73 m 2 . CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1–5 and CKD stages 3–5 prevalence across European study populations. The adjusted CKD stages 1–5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3–5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.
Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype
Authors: Mariana Conceição, Liliana Mendonça, Clévio Nóbrega, Célia Gomes, Pedro Costa, Hirokazu Hirai, João Nuno Moreira, Maria C. Lima, N. Manjunath, Luís Pereira de Almeida
Journal: Biomaterials (2015)
Outcome of salvage therapy for relapsed or refractory peripheral T-cell lymphoma (PTCL), anaplastic large cell lymphoma (ALCL), and diffuse large B-cell lymphoma (DLBCL)
Authors: G. Wu, J. Kuruvilla, T. Nagy, A. Keating, M. Crump
Journal: Journal of Clinical Oncology (2006)

6544 Background: Compared to patients with ALCL and DLBCL, PTCL patients have a lower response and higher relapse rate following anthracycline-based chemotherapy. However, in the case of relapsed or primary refractory disease, it is unclear if response to salvage treatment and survival are similarly inferior. Methods: Between 01/01/1995 and 12/30/2004, 45 patients with PTCL, 21 with ALCL, and 171 with DLBCL were referred to our institution for consideration of ASCT. The majority of patients (70%) received a platinum-based salvage regimen. Responding patients then received high-dose etoposide and melphalan followed by autologous stem cell transplant (ASCT). Results: The three groups were similar in age (median 53, range: 19–66), but PTCL patients had more advanced stage disease (III or IV) at salvage than ALCL and DLBCL (71 vs. 61 vs. 48%, p=0.03). Response rates to salvage chemotherapy were similar: 53% for PTCL, 57% for ALCL, and 53% for DLBCL (p=0.94). For T-cell (PTCL and ALCL) patients, there was a trend to better response if a platinum-based regimen was given (61 vs. 35%, p=0.06). Post-transplant, 9/21 PTCL, 3/11 ALCL, and 41/88 DLBCL patients relapsed (43 vs. 27 vs. 46%, p=0.47). Two-year event-free survival (EFS) rates were 28% (95% CI: 14–42%) for PTCL, 45% (23–67%) for ALCL, and 45% (37–53%) for DLBCL (p=0.068). Event-free and overall survival for all patients, and for those who proceeded to ASCT, are shown in the table . Conclusions: Two-year EFS is inferior for patients with relapsed/refractory PTCL treated with the intention of proceeding to ASCT, compared to ALCL and DLBCL, as is 2-year OS rate. However, PTCL patients had similar response to primarily platinum-based salvage chemotherapy, and achieved similar outcome post-ASCT. These findings suggest that strategies to improve the outcome of PTCL patients may include changes to first-line treatment and salvage regimens. [Table: see text] No significant financial relationships to disclose.
Unusual pattern of bacterial ice nucleation gene evolution.
Authors: A R Edwards, R A Van den Bussche, H A Wichman, C S Orser
Journal: Molecular Biology and Evolution (1994)

Bacterial ice nucleation activity (INA+ phenotype) can be traced to the product of a single gene, ina. A remarkably sparse distribution of this phenotype within three bacterial genera indicates that the ina gene may have followed an unusual evolutionary path. Southern blot analyses, coupled with assays for ice-nucleating ability, revealed that within four bacterial species an ina gene is present in some strains but absent from others. Results of hybridization experiments using DNA fragments that flank the ina gene suggested that the genotypic dimorphism of ina may be anomalous. A phylogenetic analysis of 16S ribosomal RNA gene sequences from a total of 14 ina+ and ina- bacterial strains indicated that the ina+ bacteria are not monophyletic but instead phylogenetically interspersed among ina- bacteria. The relationships of ina+ bacteria inferred from ina sequence did not coincide with those inferred from the 16S data. These results suggest the possibility of horizontal transfer in the evolution of bacterial ina genes.
Distinguishing benign from pathologic TH2 immunity in atopic children
Authors: Patrick G. Holt, Deborah Strickland, Anthony Bosco, Danielle Belgrave, Belinda Hales, Angela Simpson, Elysia Hollams, Barbara Holt, Merci Kusel, Staffan Ahlstedt, Peter D. Sly, Adnan Custovic
Journal: Journal of Allergy and Clinical Immunology (2015)
Detection of bone marrow involvement in breast cancer with magnetic resonance imaging.
Authors: S M Sanal, F W Flickinger, M J Caudell, R M Sherry
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the value of magnetic resonance imaging (MRI) in detecting bone marrow metastases in patients with breast cancer. PATIENTS AND METHODS Twenty-three patients with breast cancer in various stages (stage IV, 11; stage III, five; stage II, seven) were evaluated for bone marrow involvement. MRIs of marrow from lumbar spine, pelvis, and proximal femora were obtained with a 1.5-Tesla unit. All patients underwent bilateral bone marrow aspirations and biopsies for histologic evaluation and immunostaining with monoclonal antibody (MoAB) against low-molecular weight cytokeratin (CAM 5.2). Marrow MRI findings were compared with technetium 99m bone scans. Patients with stage II or III disease were monitored for clinical outcome. Possible correlation of MRI findings with serum alkaline phosphatase level was explored. RESULTS Fourteen of 23 patients showed MRI abnormalities suggestive of metastatic marrow disease (stage IV, nine; stage III, two; stage II, three). In six patients with abnormal MRIs, histology and MoAB immunostaining confirmed marrow involvement (stage IV, five; stage III, zero; stage II, one). In the other eight patients with MRI abnormalities, neither of these methods confirmed the presence of marrow metastasis. Four of five operable breast cancer (stage II-III) patients with an abnormal initial MRI showed additional abnormalities on follow-up examination and developed metastatic disease within 5 to 18 months demonstrable by conventional clinical methods. Conversely, none of the operable patients with negative MRIs developed recurrent disease at 3 to 16 months (Student's t test, P = .01). Nine patients with a normal MRI had no evidence of marrow involvement with histologic or MoAB immunostaining (stage IV, two; stage III, two; stage II, five). Of 14 patients with abnormal MRIs, bone scans were normal in seven and failed to show corresponding abnormalities in six. Elevated serum alkaline phosphatase levels showed a direct relationship with abnormal bone scans indicating extensive bony involvement, but failed to correlate with positive marrow MRIs. CONCLUSION MRI is a promising new technique to detect occult marrow involvement in breast cancer patients. There is a good correlation between abnormal marrow MRI and early development of clinical metastatic disease in patients with stage II to III disease.
Abstract 19648: Amino-Terminal Pro-Brain Natriuretic Peptide Improves Risk Stratification in Asymptomatic Individuals at Very High Risk of Future Cardiovascular Events
Authors: Anna P Pilbrow, Chris M Frampton, A M Richards, Richard W Troughton, Vicky A Cameron
Journal: Circulation (2014)

Background: In the general population, screening for risk of future cardiovascular events is performed using established risk scores based on traditional risk factors. Previous studies suggest that amino-terminal pro-brain natriuretic peptide (NT-proBNP) may provide additional prognostic information on incident cardiovascular events in the general population. Aim: This study investigated whether NT-proBNP could improve risk prediction among asymptomatic individuals with a very high risk of future cardiovascular events (Framingham risk score ≥30%). Methods: Middle-age and older participants with no history of cardiovascular disease or heart failure were recruited from the general population (n=1244, mean age 64.9±10.2 years, 69% male). Fatal/non-fatal cardiovascular events were recorded over 5 years follow-up. Associations between plasma NT-proBNP at baseline, Framingham risk score and cardiovascular events were tested with Cox regression and log-rank tests. Results: A total of 194 (16%) participants experienced a fatal/non-fatal cardiovascular event within 5 years. For all participants, higher levels of NT-proBNP were strongly associated with fatal/non-fatal cardiovascular events (event rates for NT-proBNP tertiles: 6%, 13%, 27% log-rank p&lt;0.001). This association was independent of the Framingham risk score (p&lt;0.001). The majority of events (117 events, 60%) occurred among participants with a Framingham risk score ≥30% (380 participants), among whom NT-proBNP conferred an even greater prognostic advantage: those with the highest NT-proBNP levels were at markedly increased risk (event rates for NT-proBNP tertiles: 17%, 28%, 38%, log-rank p=0.006, Figure 1). Conclusions: These data suggest that plasma NT-proBNP may significantly improve risk stratification among asymptomatic individuals of middle-older age identified as having a very high risk of future cardiovascular events according to established risk scores.
Double-Blind Phase III Randomized Trial of the Antiprogestin Agent Mifepristone in the Treatment of Unresectable Meningioma: SWOG S9005
Authors: Yongli Ji, Cathryn Rankin, Steven Grunberg, Andy E. Sherrod, Jamshid Ahmadi, Jeannette J. Townsend, Lynn G. Feun, Ruth K. Fredericks, Christy A. Russell, Fairooz F. Kabbinavar, Keith J. Stelzer, Anne Schott, Claire Verschraegen
Journal: Journal of Clinical Oncology (2015)

Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma.Eligible patients were randomly assigned to receive either mifepristone or placebo for 2 years unless disease progressed. Patients who were stable or responding to protocol therapy after 2 years had the option to continue with the same blinded therapy. Serial follow-up allowed assessment of efficacy and toxicity. Time to treatment failure and overall survival were ascertained for all randomly assigned patients. On progression, patients receiving placebo could cross over and receive active drug.Among 164 eligible patients, 80 were randomly assigned to mifepristone and 84 to placebo. Twenty-four patients (30%) were able to complete 2 years of mifepristone without disease progression, adverse effects, or other reasons for discontinuation. Twenty-eight patients (33%) in the placebo arm completed the 2-year study. There was no statistical difference between the arms in terms of failure-free or overall survival.Long-term administration of mifepristone was well tolerated but had no impact on patients with unresectable meningioma.
Final Report Of Phase II Study Of Sorafenib and 5-Azacytidine In Patients With Relapsed Or Untreated Acute Myeloid Leukemia and FLT3-ITD mutation
Authors: Maro Ohanian, Mark Levis, Stefan H. Faderl, Guillermo Garcia-Manero, Elias Jabbour, Naval G. Daver, Sara E Dellasala, Sherry Pierce, Jan A. Burger, Jorge E. Cortes, Hagop M. Kantarjian, Farhad Ravandi
Journal: Blood (2013)
A phase I dose escalation study of imatinib mesylate plus standard-dosed temozolomide in the treatment of patients with malignant glioma
Authors: S. Sathornsumetee, D. A. Reardon, J. Quinn, J. N. Rich, J. J. Vredenburgh, A. Desjardins, S. Gururangan, P. Lyons, A. Salvado, H. S. Friedman
Journal: Journal of Clinical Oncology (2005)

1540 Imatinib mesylate (Gleevec), an inhibitor of the PDGF receptor tyrosine kinase with anti-angiogenic activity, has been shown to decrease tumor interstitial pressure resulting in enhanced delivery of cytotoxic therapy. The current phase I study is designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate when combined with temozolomide, a DNA methylator with established anti-glioma activity, in patients with malignant glioma. Eligibility criteria include: histologically confirmed malignant glioma; age at least 18 years; KPS of at least 60%; less than grade 2 intratumoral hemorrhage; adequate hepatic, renal, and bone marrow function and lack of prior failure or significant toxicity following treatment with either imatinib mesylate or temozolomide. Temozolomide is dosed at 200 mg/m2 on days 1–5 of each 28-day cycle. Imatinib mesylate is administered on days 1–8 of each cycle and the dose is escalated in successive cohorts of 3–6 patients via a standard “3+3” dose escalation design. Patients are stratified based on concurrent use of enzyme-inducing anticonvulsants (EIAC; phenytoin, carbamazepine and phenobarbitol) and both strata are independently escalated. To date 15 patients have been enrolled including 13 with GBM and 2 with AA. Median age is 54.8 years (range 32 to 68); 67% are male and 33% are on EIAC. The MTD has yet to be defined for either stratum and further accrual and dose escalation are ongoing. To date no DLTs have been observed. Pharmacokinetic sampling has been performed in approximately half of the patients. Ten patients remain on study having undergone 1–5 cycles of therapy while 5 patients have developed progressive disease and discontinued therapy. An update of the outcome and toxicity of imatinib mesylate plus temozolomide for patients with recurrent malignant glioma will be presented based on additional follow up and enrollment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
p53 mutations in gastrointestinal stromal tumor: Pattern and prognostic significance
Authors: M.-H. Ryu, H. Lee, T. W. Kim, H.-M. Chang, J.-S. Kim, W.-K. Kim, J.-S. Lee, Y.-K. Kang
Journal: Journal of Clinical Oncology (2004)

9026 Background: Mutational activation of c-kit gene is recognized as a relatively early event in GIST tumorigenesis, and additional genetic alteration is needed for malignant transformation of GIST. The objective of this study was to evaluate the pattern and prognostic significance of p53 mutation as an additional genetic change. Methods: Previously, we analyzed c-kit mutations and clinical characteristics of 86 localized GISTs which were curatively resected between Jan 1990 and Dec 2001, and observed that presence of c-kit mutation and mitosis ≥ 5/50 HPF were independent poor prognostic factors for relapse-free survival (Kim, et al. Proc ECCO 2003). For these cases, clinical data were updated, and mutation analyses for p53 exons 4, 5, 6, 7, and 8 were performed with PCR and direct sequencing. Results: In 64 cases, p53 mutations were fully analyzed at exons 4, 5, 6, 7, and 8. Polymorphism at exon 4 was observed in 27 cases. P53 mutations were found in 19 (29.7%) cases; 4 in exon 4, 3 in exon 5, 6 in exon 6, 2 in exon 7, and 4 in exon 8, respectively. All were missense mutations in a single amino acid. Fifteen (31.3%) out of 48 patients with c-kit mutation and 4 (25.0%) out of 16 patients without c-kit mutation had p53 mutation (p = 0.785). By univariate analyses for relapse-free survival, mitosis (< 5/50 HPF vs. ≥ 5/50 HPF), tumor size (< 5cm vs. ≥ 5cm), c-kit mutation (presence vs. absence), cell type (spindle cell vs. others), necrosis (presence vs. absence), and cellularity (dense vs. sparse) were statistically significant factors. Multivariate analysis including p53 mutation (presence vs. absence) and above factors showed that mitosis ≥ 5/50 HPF (p = 0.0001), presence of c-kit mutation (p =0.02), presence of p53 mutation (p = 0.002) were significant independent poor prognostic factors for relapse-free survival. Conclusions: P53 mutation was found in a proportion of GISTs, and evenly distributed from exon 4 to exon 8 without any specific hot spots. P53 mutation was identified as an independent poor prognostic factor for relapse in addition to c-kit mutation and high mitosis in localized GISTs. P53 mutation may have a role in the malignant transformation of GISTs. No significant financial relationships to disclose.
Response to Letter Regarding Article “Transdifferentiation of Human Fibroblasts to Endothelial Cells: Role of Innate Immunity”
Authors: John P. Cooke, Shu Meng, Wing Tak Wong, Nazish Sayed, Frank Ospino, Jieun Lee, Arshi Jha, Philip Dexheimer, Bruce Aronow
Journal: Circulation (2015)

We thank Drs Li and Hao for their thoughtful comments on our recent article on the role of innate immunity in transdifferentiation of human fibroblasts to endothelial cells. 1 They correctly state that the epigenetic landscape is different from one somatic cell to another and that the determinants of that epigenetic landscape (such as small RNAs, transcriptional factors, and chromatin modifiers) also differ from one somatic cell to another.Accordingly, they pose an excellent question: Because of the known differences between somatic cells in their epigenetic landscape and regulation, what role does innate immune signaling play in the transdifferentiation of other somatic cells?In the absence of direct experimental evidence, we believe that we have identified a common mechanism for epigenetic plasticity that is triggered by inflammatory signaling.We call this process transflammation. 2 It is likely that this process of transflammation occurs naturally.At sites of chronic inflammation, a change in phenotype of the resident cells is often observed.For example, with chronic esophagitis caused by gastroesophageal reflux disease, the stratified squamous esophageal epithelium transdifferentiates into a columnar epithelium resembling that of the small intestine. 3This so-called Barret esophagus may later be the site of malignant transformation.Whereas chronic inflammation may be the site of pathological changes in cell phenotype, we believe that inflammatory signaling that is transient and physiological provides for therapeutic transdifferentiation. Indeed, it was recently reported that after experimental myocardial infarction, fibroblasts may transdifferentiate into endothelial cells, increasing microvascular density in response to the ischemic injury. 4omatic cells detect pathogen-or damage-associated molecular patterns by means of pattern recognition receptors such as Toll-like receptors. 5Activation of pattern recognition receptors triggers the generation and release of cytokines and chemokines that contribute to the inflammatory response.We have found that activation of pattern recognition receptors also causes global changes in epigenetic modifiers that favor an open chromatin configuration.The resulting increase in epigenetic plasticity permits somatic cells to reach into their genetic toolbox to pull out what they need to adapt and survive.Further elucidation of the mechanisms of transflammation will permit its therapeutic modulation in the treatment of chronic diseases, infection, and cancer.
Geographical variation and correlates of tobacco smoking, second-hand smoke exposure, workplace tobacco prohibition, and pro-tobacco and counter-tobacco advertising in mainland China: a cross-sectional study of 98 058 participants
Authors: Thomas Astell-Burt, Mei Zhang, Xiaoqi Feng, Limin Wang, Yichong Li, Andrew Page, Maigeng Zhou, Linhong Wang
Journal: The Lancet (2015)
Commentary on “Upper arm circumference is associated with race performance in ultra-endurance runnersUpper arm circumference is associated with race performance in ultra-endurance runners”
Authors: Christoph Josef Raschka
Journal: British Journal of Sports Medicine (2008)

<h3>Abstract</h3> Evidence from prior studies of cutaneous trauma, burns, and chronic diabetic wound repair demonstrates that endothelial progenitor cells (EPCs) contribute to <i>de novo</i> angiogenesis, anti-inflammatory reactions, tissue regeneration, and remodeling. We have shown that IL-10, a potent anti-inflammatory cytokine, promotes regenerative tissue repair in an adult model of dermal scar formation via the regulation of fibroblast-specific hyaluronan synthesis in a STAT3 dependent manner. While it is known that IL-10 drives EPC recruitment and neovascularization after myocardial infarction, its specific mode of action, particularly in dermal wound healing and neovascularization in both control and diabetic wounds remains to be defined. Here we show that IL-10 promotes EPC recruitment into the dermal wound microenvironment to facilitate neovascularization and wound healing of control and diabetic (db/db) wounds via vascular endothelial growth factor (VEGF) and stromal-cell derived factor 1 (SDF-1α) signaling. Inducible skin-specific STAT3 knockout (KO) mice were studied to determine whether the impact of IL-10 on the neovascularization and wound healing is STAT3 dependent. We found that IL-10 treatment significantly promotes dermal wound healing with enhanced wound closure, robust granulation tissue formation and neovascularization. This was associated with elevated wound EPC counts as well as increased VEGF and high SDF-1α levels in control mice, an effect that was abrogated in STAT3 KO transgenic mice. These findings were supported <i>in vitro</i>, wherein IL-10-enhanced VEGF and SDF-1α synthesis in primary murine dermal fibroblasts. IL-10-conditioned fibroblast media was shown to promote sprouting and network formation in aortic ring assays. We conclude that overexpression of IL-10 in the wound-specific milieu recruits EPCs and promote neovascularization, which occurs in a STAT3-dependent manner via regulation of VEGF and SDF-1α levels. Collectively, our studies demonstrate that IL-10 increases EPC recruitment leading to enhanced neovascularization and healing of dermal wounds.
Why we assume it's all good: The role of theory of mind in early inherent feature inferences
Authors: Karen Bartsch, David Estes
Journal: Behavioral and Brain Sciences (2014)

Abstract Cimpian &amp; Salomon's (C&amp;S's) characterization of a domain-general inherence heuristic, available to young children, underplays the importance of our early interest in and recognition of agency, intentionality, and mental life. A consideration of the centrality of desires, goals, and agency in our earliest reasoning suggests an alternative, perhaps complementary, account of our tendency to be satisfied with the status quo.