tbuckley/cabot-search huggingface dataset:
Racial/Ethnic Differences in the Prevalence of Proteinuric and Nonproteinuric Diabetic Kidney Disease
Authors: Vivek Bhalla, Beinan Zhao, Kristen M.J. Azar, Elsie J. Wang, Sarah Choi, Eric C. Wong, Stephen P. Fortmann, Latha P. Palaniappan
Journal: Diabetes Care (2012)

To examine racial/ethnic differences in the prevalence of diabetic kidney disease (DKD), with and without proteinuria, in an outpatient health care organization.We examined electronic health records for 15,683 persons of non-Hispanic white (NHW), Asian (Asian Indian, Chinese, and Filipino), Hispanic, and non-Hispanic black (NHB) race/ethnicity with type 2 diabetes and no prior history of kidney disease from 2008 to 2010. We directly standardized age- and sex-adjusted prevalence rates of proteinuric DKD (proteinuria with or without low estimated glomerular filtration rate [eGFR]) or nonproteinuric DKD (low eGFR alone). We calculated sex-specific odds ratios of DKD in racial/ethnic minorities (relative to NHWs) after adjustment for traditional DKD risk factors.Racial/ethnic minorities had higher rates of proteinuric DKD than NHWs (24.8-37.9 vs. 24.8%) and lower rates of nonproteinuric DKD (6.3-9.8 vs. 11.7%). On adjusted analyses, Chinese (odds ratio 1.39 for women and 1.56 for men), Filipinos (1.57 for women and 1.85 for men), Hispanics (1.46 for women and 1.34 for men), and NHBs (1.50 for women) exhibited significantly (P < 0.01) higher odds of proteinuric DKD than NHWs. Conversely, Chinese, Hispanic, and NHB women and Hispanic men had significantly lower odds of nonproteinuric DKD than NHWs.We found novel racial/ethnic differences in DKD among patients with type 2 diabetes. Racial/ethnic minorities were more likely to have proteinuric DKD and less likely to have nonproteinuric DKD. Future research should examine diverse DKD-related outcomes by race/ethnicity to inform targeted prevention and treatment efforts and to explore the etiology of these differences.
The long-term maintenance of cytotoxic T cell memory does not require persistence of antigen.
Authors: A Müllbacher
Journal: The Journal of Experimental Medicine (1994)

I have used the transfer of primed lymphocytes into syngeneic irradiated recipients to investigate whether the persistence of antigen is required in the long-term maintenance of cytolytic T cell memory to influenza virus. Animals were immunized with influenza virus (A/WSN) and used 17 wk later as either donors for T cells or as lethally irradiated recipients. Naive age-matched mice served as controls. At intervals of 4, 8, 16, and 25 wk after T cell transfer, experimental and control groups were immunized with a heterologous virus (A/JAP) and splenocytes tested for lytic activity to influenza virus 3 and 6 d after immunization. Lytic activity 3 d after infection (a property exclusive to a memory cytotoxic T cell response) (Effros, R. B., J. Bennink, and P. C. Doherty. 1978. Cell. Immunol. 36:345.; and Hill, A. B., R. V. Blanden, C. R. Parrish, and A. Müllbacher. 1992. Immunol. Cell Biol. 70:259), was only observed by primed and naive irradiated recipients reconstituted with memory T cells. No day 3 responses were observed when naive T cells were transferred into irradiated primed or unprimed recipients. These observations demonstrate that cytolytic T cell memory to influenza virus is long lived in the absence of antigen.
Inhibitors of Deacetylases Suppress Oncogenic KIT Signaling, Acetylate HSP90, and Induce Apoptosis in Gastrointestinal Stromal Tumors
Authors: Thomas Mühlenberg, Yixiang Zhang, Andrew J. Wagner, Florian Grabellus, James Bradner, Georg Taeger, Hauke Lang, Takahiro Taguchi, Martin Schuler, Jonathan A. Fletcher, Sebastian Bauer
Journal: Cancer Research (2009)

Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor A (PDGFRA), and treatment with the tyrosine kinase inhibitor imatinib yields responses in the majority of patients. However, most patients develop secondary resistance, which is associated with a dismal prognosis. Histone deacetylase inhibitors (HDACI) have been shown to enhance imatinib activity in imatinib-resistant chronic myelogenous leukemia. Against this background, we explored whether HDACI might provide an alternative therapeutic strategy to KIT/PDGFRA kinase inhibitors in GIST. Inhibition of cell proliferation by HDACI was seen in KIT-positive but not in KIT-negative GIST cell lines, suggesting that HDACI activity is mainly conferred by targeting oncogenic KIT. KIT activity, expression, and activation of downstream pathways were strongly inhibited by several HDACI (SAHA, LBH589, VPA, trichostatin A, and NaButyrate). SAHA and LBH589 induced apoptosis in KIT-positive GIST, and strong synergism with imatinib was observed at low concentrations of SAHA and LBH589. Mechanistically, treatment with HDACI reduced KIT mRNA transcript levels and led to strong acetylation of HSP90, interfering with its activity as KIT chaperone. These results provide preclinical evidence for a disease-specific effect of HDACI in KIT-positive GIST, which could translate into therapeutic activity.
Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study
Authors: Charles S. Fuchs, John Marshall, Edith Mitchell, Rafal Wierzbicki, Vinod Ganju, Mark Jeffery, Joseph Schulz, Donald Richards, Raoudha Soufi-Mahjoubi, Benjamin Wang, José Barrueco
Journal: Journal of Clinical Oncology (2007)

This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of > or = grade 3 hypertension than mIFL+Bev.FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.
Phosphoinositide-3 Kinase γ Activity Contributes to Sepsis and Organ Damage by Altering Neutrophil Recruitment
Authors: Erica L. Martin, Danielle G. Souza, Caio T. Fagundes, Flavio A. Amaral, Barbara Assenzio, Valeria Puntorieri, Lorenzo Del Sorbo, Vito Fanelli, Martino Bosco, Luisa Delsedime, Jose F. Pinho, Virginia S. Lemos, Fabricio O. Souto, Jose C. Alves-Filho, Fernando Q. Cunha, Arthur S. Slutsky, Thomas Ruckle, Emilio Hirsch, Mauro M. Teixeira, V. Marco Ranieri
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Sepsis is a leading cause of death in the intensive care unit, characterized by a systemic inflammatory response (SIRS) and bacterial infection, which can often induce multiorgan damage and failure. Leukocyte recruitment, required to limit bacterial spread, depends on phosphoinositide-3 kinase γ (PI3Kγ) signaling in vitro; however, the role of this enzyme in polymicrobial sepsis has remained unclear.This study aimed to determine the specific role of the kinase activity of PI3Kγ in the pathogenesis of sepsis and multiorgan damage.PI3Kγ wild-type, knockout, and kinase-dead mice were exposed to cecal ligation and perforation-induced sepsis and assessed for survival; pulmonary, hepatic, and cardiovascular damage; coagulation derangements; systemic inflammation; bacterial spread; and neutrophil recruitment. Additionally, wild-type mice were treated either before or after the onset of sepsis with a PI3Kγ inhibitor and assessed for survival, neutrophil recruitment, and bacterial spread.Both genetic and pharmaceutical PI3Kγ kinase inhibition significantly improved survival, reduced multiorgan damage, and limited bacterial decompartmentalization, while modestly affecting SIRS. Protection resulted from both neutrophil-independent mechanisms, involving improved cardiovascular function, and neutrophil-dependent mechanisms, through reduced susceptibility to neutrophil migration failure during severe sepsis by maintaining neutrophil surface expression of the chemokine receptor, CXCR2. Furthermore, PI3Kγ pharmacological inhibition significantly decreased mortality and improved neutrophil migration and bacterial control, even when administered during established septic shock.This study establishes PI3Kγ as a key molecule in the pathogenesis of septic infection and the transition from SIRS to organ damage and identifies it as a novel possible therapeutic target.
Mortality in Concurrent Type 1 Diabetes and Anorexia Nervosa
Authors: Søren Nielsen, Charlotte Emborg, Anne-Grethe Mølbak
Journal: Diabetes Care (2002)

Previous studies in this field report early occurrence of diabetic complications, but excess mortality, though expectable, has not been reported. We combined information from earlier studies to estimate the mortality for this group of patients.The observed mortality is analyzed using crude mortality rate (a percentage), standardized mortality ratio (SMR), incidence rate ratio, risk difference, and survival analysis.After approximately 10 years of follow-up, 13 of 510 females with type 1 diabetes, 43 of 658 females with anorexia nervosa (AN), and 8 of 23 concurrent case subjects had died. Mortality rate was 2.2 (per 1,000 person-years) for type 1 diabetes, 7.3 for AN cases, and 34.6 for concurrent cases. Crude mortality rates were 2.5, 6.5, and 34.8%, respectively. SMR was 4.06 in type 1 diabetes, 8.86 in AN, and 14.5 in concurrent cases. Survival analysis indicated between-group differences in mortality.Concurrent type 1 diabetes and AN is a rare but serious condition in females. All indexes of mortality evidence excess mortality in this preliminary study. Vigorous and well-directed treatment efforts seem vital for this subpopulation. Collaboration between diabetologists and eating disorder specialists is warranted. The implications of other eating disorders and subclinical eating disorders in diabetic populations need to be analyzed, especially because these conditions are more frequent than clinical eating disorders.
Plasma vitamin A levels in the common dermatoses
Authors: P.D. MIER, JOSE J.M.A. HURK
Journal: British Journal of Dermatology (1974)

The plasma vitamin A levels of 164 patients with skin disease and 102 comparable control subjects were measured by means of a modern fluorimetric technique. No correlation was found between plasma vitamin A levels and skin disease in adults. A low or marginal vitamin A status, however, was observed in about one‐third of skin patients younger than 20 years.
The genetic landscape of high-risk neuroblastoma
Authors: Trevor J Pugh, Olena Morozova, Edward F Attiyeh, Shahab Asgharzadeh, Jun S Wei, Daniel Auclair, Scott L Carter, Kristian Cibulskis, Megan Hanna, Adam Kiezun, Jaegil Kim, Michael S Lawrence, Lee Lichenstein, Aaron McKenna, Chandra Sekhar Pedamallu, Alex H Ramos, Erica Shefler, Andrey Sivachenko, Carrie Sougnez, Chip Stewart, Adrian Ally, Inanc Birol, Readman Chiu, Richard D Corbett, Martin Hirst, Shaun D Jackman, Baljit Kamoh, Alireza Hadj Khodabakshi, Martin Krzywinski, Allan Lo, Richard A Moore, Karen L Mungall, Jenny Qian, Angela Tam, Nina Thiessen, Yongjun Zhao, Kristina A Cole, Maura Diamond, Sharon J Diskin, Yael P Mosse, Andrew C Wood, Lingyun Ji, Richard Sposto, Thomas Badgett, Wendy B London, Yvonne Moyer, Julie M Gastier-Foster, Malcolm A Smith, Jaime M Guidry Auvil, Daniela S Gerhard, Michael D Hogarty, Steven J M Jones, Eric S Lander, Stacey B Gabriel, Gad Getz, Robert C Seeger, Javed Khan, Marco A Marra, Matthew Meyerson, John M Maris
Journal: Nature Genetics (2013)
Off-Pump or On-Pump Coronary-Artery Bypass Grafting at 30 Days
Authors: André Lamy, P.J. Devereaux, Dorairaj Prabhakaran, David P. Taggart, Shengshou Hu, Ernesto Paolasso, Zbynek Straka, Leopoldo S. Piegas, Ahmet Ruchan Akar, Anil R. Jain, Nicolas Noiseux, Chandrasekar Padmanabhan, Juan-Carlos Bahamondes, Richard J. Novick, Prashant Vaijyanath, Sukesh Reddy, Liang Tao, Pablo A. Olavegogeascoechea, Balram Airan, Toomas-Andres Sulling, Richard P. Whitlock, Yongning Ou, Jennifer Ng, Susan Chrolavicius, Salim Yusuf
Journal: New England Journal of Medicine (2012)

The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established.
Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection
Authors: Galit Alter, Nickolas Teigen, Benjamin T. Davis, Marylyn M. Addo, Todd J. Suscovich, Michael T. Waring, Hendrik Streeck, Mary N. Johnston, Kyle D. Staller, M. Tauheed Zaman, Xu G. Yu, Mathias Lichterfeld, Nesli Basgoz, Eric S. Rosenberg, Marcus Altfeld
Journal: Blood (2005)
Parasympathetic dysfunction in rheumatoid arthritis patients with ocular dryness.
Authors: P J Barendregt, G L van der Heijde, F C Breedveld, H M Markusse
Journal: Annals of the Rheumatic Diseases (1996)

To determine whether abnormalities in the function of the autonomic nervous system are associated with oral and ocular dryness in rheumatoid arthritis.Pupillography was done using an infrared light reflection method (IRIS) to measure both parasympathetic function (constriction latency and the latency of maximum constriction velocity (MCV)) and sympathetic function (dilatation latency) in rheumatoid arthritis patients with and without ocular dryness. The Schirmer and Saxon tests were used to measure the tear and saliva production respectively.The Schirmer and Saxon test results in rheumatoid arthritis patients with ocular dryness were reduced (P < 0.05) compared with rheumatoid arthritis patients without ocular dryness and healthy controls. Constriction latency and MCV latency were prolonged in rheumatoid arthritis patients with ocular dryness compared to the other two groups (P < 0.05). A negative correlation was found between the degree of ocular dryness and both constriction latency and MCV latency. No correlation was found between the results of pupillography and saliva production.Parasympathetic dysfunction may play a role in ocular dryness in patients with rheumatoid arthritis.
Isolated hyperferritinemia is associated with liver iron overload, liver steatosis and dyslipidemia
Authors: M. Viganò, A. Vergani, L. Parma, I. Malosio, A. Salvioni, N. Caronni, V. Arosio, G. Bovo, C. Arosio, A. Piperno
Journal: Journal of Hepatology (1998)
Human papillomavirus 6 seropositivity is associated with risk of head and neck squamous cell carcinoma, independent of tobacco and alcohol use
Authors: C.S. Furniss, M.D. McClean, J.F. Smith, J. Bryan, K.M. Applebaum, H.H. Nelson, M.R. Posner, K.T. Kelsey
Journal: Annals of Oncology (2008)
Sirt1 ablation promotes stress-induced loss of epigenetic and genomic hematopoietic stem and progenitor cell maintenance
Authors: Satyendra K. Singh, Carrie A. Williams, Kimberly Klarmann, Sandra S. Burkett, Jonathan R. Keller, Philipp Oberdoerffer
Journal: The Journal of Experimental Medicine (2013)

The (histone) deacetylase Sirt1 is a mediator of genomic and epigenetic maintenance, both of which are critical aspects of stem cell homeostasis and tightly linked to their functional decline in aging and disease. We show that Sirt1 ablation in adult hematopoietic stem and progenitor cells (HSPCs) promotes aberrant HSPC expansion specifically under conditions of hematopoietic stress, which is associated with genomic instability as well as the accumulation of DNA damage and eventually results in a loss of long-term progenitors. We further demonstrate that progenitor cell expansion is mechanistically linked to the selective up-regulation of the HSPC maintenance factor and polycomb target gene Hoxa9. We show that Sirt1 binds to the Hoxa9 gene, counteracts acetylation of its histone target H4 lysine 16, and in turn promotes polycomb-specific repressive histone modification. Together, these findings demonstrate a dual role for Sirt1 in HSPC homeostasis, both via epigenetic regulation of a key developmental gene and by promoting genome stability in adult stem cells.
Epidemiological and virological assessment of influenza activity in Europe during the winter 2005-2006
Authors: A Meijer, T J Meerhoff, L. E. Meuwissen, J Van Der Velden, W J Paget, None European Influenza Surveillance Scheme (EISS)
Journal: Eurosurveillance (2007)

Influenza activity in Europe during the winter 2005-2006 started late January - early February 2006 and first occurred in the Netherlands, France, Greece and England. Subsequently, countries were affected in a random pattern across Europe and the period of influenza activity lasted till the end of April. In contrast to the winter seasons in the period 2001-2005, no west-east pattern was detected. In 12 out of 23 countries, the consultation rates for influenza-like illness or acute respiratory infection in the winter 2005-2006 were similar or higher than in the winter 2004-2005, despite a dominance of influenza B viruses that normally cause milder disease than influenza A viruses. In the remaining 11 countries the consultation rates were lower to much lower than in the winter 2004-2005. The highest consultation rates were usually observed among children aged 0-14. The circulating influenza virus types and subtypes were distributed heterogeneously across Europe. Although the figures for total virus detections in Europe indicated a predominance of influenza B virus (58% of all virus detections), in many countries influenza B virus was predominant only early in the winter, whilst later there was a marked increase in influenza A virus detections. Among the countries where influenza A viruses were co-dominant with B viruses (9/29) or were predominant (4/29), the dominant influenza A subtype was H3 in seven countries and H1 in four countries. The vast majority of characterised influenza B viruses (90%) were similar to the B/Victoria/2/87 lineage of influenza B viruses that re-emerged in Europe in the winter 2004-2005 but were not included in the vaccine for the influenza season 2005-2006. This might help to explain the dominance of influenza B viruses in many countries in Europe during the winter 2005-2006. The influenza A(H3) and A(H1) viruses were similar to the reference strains included in the 2005-2006 vaccine, A/California/7/2004 (H3N2) and A/New Caledonia/20/99 (H1N1), respectively. In conclusion, the 2005-2006 influenza epidemic in Europe was characterised by moderate clinical activity, a heterogeneous spread pattern across Europe, and a variable virus dominance by country, although an overall dominance of influenza B viruses that did not match the virus strain included in the vaccine was observed.
Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients
Authors: François Blot, Thomas Similowski, Jean-Louis Trouillet, Patrick Chardon, Jean-Michel Korach, Marie-Alyette Costa, Didier Journois, Guillaume Thiéry, Muriel Fartoukh, Isabelle Pipien, Nicolas Bruder, David Orlikowski, Frédéric Tankere, Isabelle Durand-Zaleski, Christian Auboyer, Gérard Nitenberg, Laurent Holzapfel, Alain Tenaillon, Jean Chastre, Agnès Laplanche
Journal: Intensive Care Medicine (2008)
The lectin-like domain of thrombomodulin hampers host defence in pneumococcal pneumonia
Authors: Marcel Schouten, J. Daan de Boer, Cornelis van ’t Veer, Joris J.T.H. Roelofs, Joost C.M. Meijers, Marcel Levi, Edward M. Conway, Tom van der Poll
Journal: European Respiratory Journal (2012)

The lectin-like domain of thrombomodulin (TM) plays an important regulatory role in sterile inflammatory conditions, but its role in severe Gram-positive infectious disease is unknown. Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. The aim of this study was to determine the role of the lectin-like domain of TM in murine pneumococcal pneumonia. Wild-type (WT) mice and mice lacking the lectin-like domain of TM (TM LeD/LeD ) were infected intranasally with viable S. pneumoniae and either observed in a survival study or euthanised 6, 24 or 48 h after infection. TM LeD/LeD mice had a markedly better survival in pneumococcal pneumonia when compared with WT mice. At 48 h post-infection with S. pneumoniae, TM LeD/LeD mice had lower bacterial loads in blood and liver, and exhibited less pulmonary inflammation, as shown by having less lung histopathology, less neutrophil influx and lower cytokine and chemokine levels. Plasma levels of pro-inflammatory cytokines were also reduced in TM LeD/LeD mice after exposure to the infection. Deletion of the lectin-like domain of TM improves the host defence in pneumococcal pneumonia. The lectin-like domain of TM may have a differential role in response to Gram-positive or Gram-negative bacteria.
Neovastat (Æ-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels
Authors: G. Batist, F. Patenaude, P. Champagne, D. Croteau, C. Levinton, C. Hariton, B. Escudier, E. Dupont
Journal: Annals of Oncology (2002)
A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation
Authors: A. Dueñas-Gonzalez, C. López-Graniel, A. González-Enciso, L. Cetina, L. Rivera, I. Mariscal, G. Montalvo, E. Gómez, J. de la Garza, G. Chanona, A. Mohar
Journal: Annals of Oncology (2003)