tbuckley/cabot-search huggingface dataset:
Abstract MP05: Life’s Simple 7 and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis
Authors: Oluseye Ogunmoroti, Ebenezer Oni, Norrina B Allen, Erica S Spatz, Jamal S Rana, Salim S Virani, Ron Blankstein, Roger S Blumenthal, Emir Veledar, Moyses Szklo, Michael J Blaha, Khurram Nasir
Journal: Circulation (2016)

Background: The concept of Life’s Simple 7 (LS7) metrics was introduced by the American Heart Association to assess and promote cardiovascular health. Individuals with favorable LS7 scores have a lower incidence of cardiovascular disease. In this study, we examined the association between the LS7 metrics and incident heart failure (HF) Methods: We analyzed data from the Multi-Ethnic Study of Atherosclerosis, a multicenter cohort study that included 6,814 participants free of established cardiovascular disease, between the ages of 45 and 84. The components of the LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were graded on a scale of 0-2, with 2 indicating “ideal” status, 1 indicating “intermediate” status and 0 indicating “poor” status. These scores were summed for each participant, thus, the LS7 score created ranged from 0 to 14. Hazard ratios and incidence rates of HF per 1000 person-years were calculated Results: After exclusion of participants with incomplete data, the final study population was 6,506 (53% female mean age 62 ±10 years). In a median follow up of 10.2 years, 181 (2.8%) participants developed HF. The incidence of HF decreased as the number of ideal LS7 metrics increased 6.5 per 1000 person-years for participants with 0-1 ideal metrics compared to 1.3 per 1000 person-years for those with 5 ideal metrics (Table). No HF event was reported in participants with 6-7 ideal metrics at baseline. In comparison to participants with 0-1 ideal metrics, having 2, 3, 4, and 5 ideal metrics was associated with an 11%, 36%, 59% and 76% lower hazard for HF respectively. In addition, optimal and average LS7 scores were associated with an 80% and 51% lower hazard for HF, respectively Conclusion: The American Heart Association LS7 metrics was associated with a lower incidence of HF in a follow up extending up to 10 years. These findings suggest that efforts to achieve ideal cardiovascular health metrics favorably reduce the risk of HF, a major source of morbidity and mortality
Development and Validation of a Predictive Model for Disease Control (Dc) at First Disease Assessment, Among Patients (Pts) with Metastatic Squamous Cell Esophageal Cancer (Mscc) Treated with First-Line Chemotherapy (Ct)
Authors: N. Kotecki, E. Tresch, N. Penel, S. Hiret, P.L. Etienne, E. Francois, M. Galais, A. Ben Abdelghani, P. Michel, L. Dahan, F. Ghiringhelli, L. Bedenne, E. Samalin, G. Piessen, J. Bennouna, C. Peugniez, F. El Hajbi, A. Kramar, C. Mariette, A. Adenis
Journal: Annals of Oncology (2014)
Prospective evaluation of early virological response associated with peginterferon alfa-2a (40KD) (Pegasys (R)) and ribavirin from a phase IV, randomized study examining the effects of treatment duration-in hepatitis C patients infected with genotype 1.
Authors: C. E. Brandao, R. Perez-Gomez, M. G. Pessoa, M. A. Olivera-Martinez, Carlos Antonio Caramori, C. V. Bazan-Perez, M. Patelli, R. Torres-Ibarra, A. Barone, M. Dehesa-Violante, F. Carrilho, R. Vivar, F. Tatsch
Journal: Hepatology (2002)
Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD
Authors: Irene H. Heijink, Harold G. de Bruin, Robin Dennebos, Marnix R. Jonker, Jacobien A. Noordhoek, Corry-Anke Brandsma, Maarten van den Berge, Dirkje S. Postma
Journal: European Respiratory Journal (2016)

Wingless/integrase-1 (WNT) signalling is associated with lung inflammation and repair, but its role in chronic obstructive pulmonary disease (COPD) pathogenesis is unclear. We investigated whether cigarette smoke-induced dysregulation of WNT-5B contributes to airway remodelling in COPD.We analysed WNT-5B protein expression in the lung tissue of COPD patients and (non)smoking controls, and investigated the effects of cigarette smoke exposure on WNT-5B expression in COPD and control-derived primary bronchial epithelial cells (PBECs). Additionally, we studied downstream effects of WNT-5B on remodelling related genes fibronectin, matrix metalloproteinase (MMP)-2, MMP-9 and SnaiI in BEAS-2B and air-liquid interface (ALI)-cultured PBECs.We observed that airway epithelial WNT-5B expression is significantly higher in lung tissue from COPD patients than controls. Cigarette smoke extract significantly increased mRNA expression of WNT-5B in COPD, but not control-derived PBECs. Exogenously added WNT-5B augmented the expression of remodelling related genes in BEAS-2B cells, which was mediated by transforming growth factor (TGF)-β/Smad3 signalling. In addition, WNT-5B upregulated the expression of these genes in ALI-cultured PBECs, particularly PBECs from COPD patients.Together, our results provide evidence that exaggerated WNT-5B expression upon cigarette smoke exposure in the bronchial epithelium of COPD patients leads to TGF-β/Smad3-dependent expression of genes related to airway remodelling.
Rationing Hospital Care
Authors: William B. Schwartz, Henry J. Aaron
Journal: New England Journal of Medicine (1984)

Resistance to the decades-long rise in the cost of hospital care in the United States is growing rapidly. In consequence, all physicians and patients soon may have to live with, and within, a system that limits expenditures. The process has, in fact, already begun. Fixed per diem reimbursement, reimbursements according to specific diagnosis, and overall revenue limits are currently being implemented by several states or by the federal government under Medicare. In addition, many businesses are pursuing cost containment through so-called preferred-provider organizations.It is unclear how far our efforts to control hospital costs will go, but one thing is . . .
TCTAP A-083 Long-Term Mortality After Coronary Artery Bypass Graft Surgery Versus Drug-Eluting Stents Implantation for Multivessel Coronary Artery Disease: Analysis of Pooled Data from the BEST and SYNTAX Trials
Authors: Mineok Chang, Jung-Min Ahn, Cheol Whan Lee, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Seong-Wook Park, Patrick W. Serruys, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2016)
<i>Notes from the Field</i>: Health Care–Associated Hepatitis A Outbreak — Texas, 2015
Authors: Rachel Wiseman, Lauren M. Weil, Catalina Lozano, Thomas J. Johnson, Sherry Jin, Anne C. Moorman, Monique A. Foster, Tonya Mixson-Hayden, Yury Khudyakov, David T. Kuhar, Julie Graves
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On August 27-28, 2015, the Texas Department of State Health Services received calls from Fort Bend County and Harris County health departments requesting postexposure prophylaxis (PEP) recommendations for contacts of two nurses (patients A and B) with confirmed hepatitis A virus (HAV) infection. Both nurses had symptom onset during August 15-19 and worked for the same pediatric home health care agency in another jurisdiction. Because of the proximity of the onset dates, a common source exposure was suspected. The state and local health departments began an investigation to identify potentially exposed patients, their families, and other agency personnel; offer PEP; and identify the source of exposure.
Update on the development of the international neuroblastoma risk group (INRG) classification schema
Authors: S. L. Cohn, W. B. London, T. Monclair, K. K. Matthay, P. F. Ambros, A. D. Pearson
Journal: Journal of Clinical Oncology (2007)

9503 Background: Modern treatment strategies for neuroblastoma (NB) are tailored according to patient risk. However, it is not currently possible to compare the results of clinical studies conducted around the globe because the criteria used to define risk are not uniform. A committee of international investigators with expertise in NB have worked during the past 2 years to develop a uniform International NB Risk Group (INRG) Classification System for pre-treatment stratification. Methods: Investigators from North America and Australia (COG); Europe (SIOPEN and Germany), and Japan collated data on 8,800 children with NB diagnosed between 1990 and 2002. Survival tree regression analyses tested 13 potential prognostic factors. Tumor differentiation, MKI, and diagnostic category were evaluated individually in lieu of the International NB Pathology Classification (INPC) system to determine if these histologic features had prognostic value independent from age. To stage patients at the time of diagnosis prior to surgery, a new staging system was developed (INRGSS) based on the presence or absence of image-defined risk factors (IDRFs) and metastases. Results: Since statistical analyses demonstrated support for an optimal age cut- off between 14–19 months, 18 months was selected. In addition to age, stage, MYCN amplification, tumor differentiation, ploidy, and genetic aberrations of 11q were found to be the most highly prognostically significant factors. These clinical and biological factors were combined to define 15 INRG pre-treatment groups. Patients with low- (3 groups), intermediate- (4 groups), high- (4 groups), or ultra-high-risk NB (4 groups) had EFS of ≥85%, &gt;70–85%, &gt;50–70%, or &lt;50%, respectively. Conclusion: International collaborative studies in NB will be greatly facilitated by the INRG classification system which will allow comparisons of different risk-based therapeutic approaches in homogeneous patient cohorts. No significant financial relationships to disclose.
Sensitivity of the Parathyroid Hormone–1, 25-Dihydroxyvitamin D Axis to Variations in Calcium Intake in Patients with Primary Hyperparathyroidism
Authors: Karl L. Insogna, MaryAnn E. Mitnick, Andrew F. Stewart, William J. Burtis, Lawrence E. Mallette, Arthur E. Broadus
Journal: New England Journal of Medicine (1985)

Original Article from The New England Journal of Medicine — Sensitivity of the Parathyroid Hormone–1, 25-Dihydroxyvitamin D Axis to Variations in Calcium Intake in Patients with Primary Hyperparathyroidism
European Collaborative Study Defining Clinical Profile Outcomes and Novel Prognostic Criteria in Monoclonal Immunoglobulin M–Related Light Chain Amyloidosis
Authors: Sajitha Sachchithanantham, Murielle Roussel, Giovanni Palladini, Catherine Klersy, Shameem Mahmood, Christopher Paul Venner, Simon Gibbs, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, Arnaud Jaccard, Giampaolo Merlini, Ashutosh D. Wechalekar
Journal: Journal of Clinical Oncology (2016)

Purpose Immunoglobulin M (IgM)–related light chain (AL) amyloidosis, which accounts for 6% to 10% of all AL amyloidosis cases, is a rare and poorly studied clinical entity. Its natural history and management is not clearly defined. Prognostic and response criteria for AL amyloidosis in general have not been validated in this population. Patients and Methods We retrospectively gathered data for 250 patients diagnosed with IgM AL amyloidosis from three European amyloidosis centers. Clinical features, hematologic response, and overall survival (OS) were analyzed. The current staging and response criteria in non-IgM AL amyloidosis was applied to this series to assess its utility in this patient cohort. Results Patients with IgM AL amyloidosis have a significant IgM paraprotein (median, 10 g/L), less frequent lambda light chain isotype, and evaluable difference between involved and uninvolved free light chains (dFLCs; &gt; 50 mg/L) in only two thirds of patients. Bone marrow showed clear non-Hodgkin lymphoma as the underlying disorder in 54% of patients. Cardiac involvement (45%) is less common but there is more frequent lymph node (20%) and neuropathic (28%) involvement compared with non-IgM AL. Fifty-seven percent of patients achieved a hematologic response (14% very good partial response/complete response [VGPR/CR]), with median OS not reached for patients achieving VGPR/CR, 64 months for PR, and 28 months for nonresponders (P &lt; .001). On multivariate analysis, cardiac involvement, advanced Mayo disease stage, neuropathic involvement, and liver involvement were independent factors that had an impact on survival. Combining abnormal N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T with liver involvement and the presence of neuropathy gives a better risk model: median OS of patients with none, one, or two or more abnormal factors was 90, 33, and 16 months, respectively. Conclusion IgM AL amyloidosis is a distinct clinical entity. Low-risk disease can be defined by combining cardiac involvement with novel prognostic markers. Deeper hematologic responses translate into improved outcomes, yet deep responses remain dismally poor, which highlights the urgent need for novel therapies.
Abstract 17343: Innate T Cells Improve Brain Injury and Mortality After Cardiac Arrest and Resuscitation
Authors: Edy Y Kim, Kohei Ikeda, Kei Hayashida, Michael B Brenner, Fumito Ichinose
Journal: Circulation (2015)

Introduction: Systemic inflammation may contribute to brain injury and mortality after cardiac arrest and resuscitation (CA/CPR). The early increase of inflammatory cytokines (such as interferon-γ [IFNγ]) suggests a role for innate immunity in CA/CPR. Natural Killer T (NKT) cells, a type of innate T cell, are “master regulators” of IFNγ and other facets of the early innate immune response in other disease models. To study the regulation of innate immunity after CA/CPR, we examined CD1dKO mice (which lack both invariant NKT cells and diverse NKT cells) and Jα18 KO mice (which lack only invariant NKT cells). Hypothesis: NKT cells control inflammation, brain injury, and mortality in CA/CPR. Methods: Mice were mechanically ventilated, underwent 8 min. of normothermic CA with potassium chloride i.v. and were resuscitated with chest compressions and epinephrine i.v. Results: Surprisingly, normally pro-inflammatory NKT cells had a protective effect. After CA/CPR, pan-NKT cell-deficient (CD1d KO) mice had markedly worsened brain injury and mortality compared to wild-type (WT) mice; but Jα18 KO mice (which only lack invariant NKT cells) had similar outcomes as WT mice. These results suggested that diverse NKT cells had a protective role after CA/CPR. Pan-NKT cell-deficient (CD1d KO) mice had exaggerated IFNγ production by NK and innate lymphoid cells (ILC1s) after CA/CPR. In line with the increased IFNγ and worsened outcomes in NKT cell-deficient mice, IFNγ-deficient (IFNγ KO) mice had improved brain injury and mortality after CA/CPR, compared to WT mice. Finally, NKT cell-deficient mice were rescued by IFNγ deficiency (Cd1d-/- Ifng-/- double KO mice). Conclusions: Unexpectedly, diverse NKT cells were anti-inflammatory and protective in CA/CPR. In CA/CPR, diverse NKT cells reduced IFNγ levels, and reduction of IFNγ improved mortality and brain injury. Innate T cells and IFNγ may be targets for therapeutic intervention in CA/CPR.
Immunochemotherapy RCHOP in patients with diffuse large B- cell lymphoma over 75 year old.
Authors: Ewa Paszkiewicz-Kozik, Joanna Romejko-Jarosinska, Michal Osowiecki, Rafal Becht, Monika Swierkowska-Czeneszew, Katarzyna Domanska-Czyz, Beata Ostrowska, Lidia Poplawska, Grzegorz Rymkiewicz, Jan Andrzej Walewski
Journal: Journal of Clinical Oncology (2015)

e19525 Background: Median age of patients (pts) with diffuse large B cell lymphoma (DLBCL) is 65 years and the prevalence of DLBCL in pts aged over 75 years is rapidly growing. In younger patients, standard induction RCHOP immunotherapy results in about 70% of cure. On the other hand, older pts are frequently considered unfit for standard RCHOP treatment, and receive reduced doses of doxorubicin or a drug substituted with other agents. Methods: Between 2007 and 2011, 69 DLBCL pts (male - 35) over 75 year old were treated with standard RCHOP induction regimen in two academic centers. Patient characteristics: median age (range) 80(76-90), ECOG PS 0-1 – 83%, more than one comorbid condition – 64%, Ann Arbor stage III/IV - 39%, extranodal involvement – 81%, elevated LDH level - 43% of pts. Median number of RCHOP cycles was 6 (range 1-8). RCHOP dose reduction, mostly doxorubicin, was required in 27 pts (39%) Results: In 65 pts evaluable for response, ORR was 95%, and CR was 66%. 25 pts were hospitalized due to treatment related complications. 19 pts died, including 9 in progressive disease, and 8 pts within 6 months from diagnosis. No treatment related deaths were reported. After a median (range) follow up of 31 months (1 - 81), median progression free survival (PFS) and overall survival (OS) was not reached for entire group. 3-year PFS and OS was 64% (95%C.I. 53%, 75%), and 67% (95%C.I. 55%, 79%). In patients with low-intermediate, high-intermediate, and high NCCN-IPI risk (Zhou et al. Blood 2014), 3 year OS was 87%, 62%, and 44%, respectively. Age over 80 years, dose reductions, and number of comorbidities were not significant for PFS or OS but ECOG PS > 1 and CS III/IV were significant negative factors for outcome. Conclusions: In pts over 75 year old with good performance status, standard RCHOP is effective induction treatment even if dose reductions are needed beyond the first cycle. Our data support RCHOP regimen as appropriate therapy for elderly patients.
Photoactive g‐C<sub>3</sub>N<sub>4</sub> Nanosheets for Light‐Induced Suppression of Alzheimer's β‐Amyloid Aggregation and Toxicity
Authors: You Jung Chung, Byung Il Lee, Jong Wan Ko, Chan Beum Park
Journal: Advanced Healthcare Materials (2016)

Graphitic carbon nitride (g-C3N4) has a suppressive capability toward Alzheimer's Aβ aggregation under light-illumination. Photoinduced electrons of g-C3N4 generate reactive oxygen resulting in photooxidation of amyloid peptides that blocks Aβ aggregation. Fe doping of g-C3N4 frameworks results in enhanced optical properties and even stronger inhibition of Aβ aggregation. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
EPIG-01THE FUNCTION OF CHROMATIN-MODIFYING ENZYMES IN GBM CELL APOPTOSIS
Authors: Ibrahim Cagri Kurt, Zeynep Kahya, Selena Kazancioglu, Ahmet Cingoz, Nathan Lack, Zeynep Hulya Gumus, Tamer Onder, Tugba Bagci Onder
Journal: Neuro-Oncology (2015)

Emerging evidence suggests that apoptotic resistance in cancers is associated with aberrant expression of the key components of the apoptotic program. However, how these components are regulated at an epigenetic level is not understood. In this study, we aimed to identify novel epigenetic mechanisms regulating the response of Glioblastoma Multiforme (GBM) cells to a pro-apoptotic ligand and an emerging therapeutic candidate, TRAIL. To this end, we conducted a short-hairpin RNA (shRNA) screen to assess the function of chromatin modifying-enzymes in TRAIL-induced apoptosis. We employed 2-3 shRNAs/gene to interrogate the role of 47 genes in DNA and histone modification pathways. Accordingly, we tested shRNAs targeting DNA-methyltransferases (DNMTs), Histone-Methyltransferases (HMTs), Histone demethylases (HDMs), Methyl-DNA binding proteins, and Polycomb complex members (PrC). Upon infection with individual shRNAs, U87MG cells were tested for their TRAIL response using cell viability assays. As a result, we identified KDM2B, an H3K36-specific HDM, as a novel regulator of TRAIL response. Accordingly, silencing of KDM2B significantly enhanced TRAIL sensitivity and accelerated the apoptosis process, as revealed by live cell imaging experiments. In order to decipher the downstream molecular pathways regulated by KDM2B, we examined expression levels of apoptosis-related genes by RNA-sequencing and quantitative PCR, and observed de-repression of pro-apoptotic genes and repression of anti-apoptotic genes upon KDM2B silencing. We also observed attenuated tumor growth upon KDM2B silencing in vivo. Taken together, our findings suggest a novel mechanism where the key apoptosis components are under epigenetic control of KDM2B in GBM cells. Therefore, identifying the direct targets of KDM2B might provide a new understanding of apoptosis response in GBMs and aid in the design of successful pro-apoptotic therapies.
Vaccines against norovirus: state of the art trials in children and adults
Authors: F. Baehner, H. Bogaerts, R. Goodwin
Journal: Clinical Microbiology and Infection (2016)

Noroviruses (NoVs), a group of nonenveloped, single-stranded RNA viruses belonging to the Caliciviridae family, are the leading cause worldwide of acute infectious gastroenteritis. Serious and eventual fatal outcomes may be observed in at-risk populations such as the very young or older adults, especially in those with underlying diseases. NoVs are highly infectious, with a low number of virus particles causing infection, and they are highly resistant to environmental conditions. NoVs have multiple routes of transmission including faecal-oral, aerosolized vomitus, person to person and via contaminated surfaces or food and water. NoVs can cause frequent and dramatic outbreaks where people congregate in close quarters such as hospitals, long-term care facilities, cruise liners and military barracks and ships. Of the seven NoV genogroups, human disease is most frequently caused by genogroups I and II, although genogroup IV has also been associated with illness. The absence of reliable, high-yield cell culture systems or animal models has steered the development of vaccines towards nonreplicating recombinant capsid proteins including viruslike particles and the sub-virus-sized P particles. Takeda Vaccines is developing a candidate NoV vaccine formulation based on adjuvanted viruslike particles from the GI.1 genotype and a consensus GII.4 sequence derived from three natural GII.4 variants. Early clinical trial results show good tolerability and robust immune responses to both components. This approach is designed to induce broad protective immune responses in adults and children.