tbuckley/cabot-search huggingface dataset:
Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data
Authors: Ary Serpa Neto, Sabrine N T Hemmes, Carmen S V Barbas, Martin Beiderlinden, Ana Fernandez-Bustamante, Emmanuel Futier, Ognjen Gajic, Mohamed R El-Tahan, Abdulmohsin A Al Ghamdi, Ersin Günay, Samir Jaber, Serdar Kokulu, Alf Kozian, Marc Licker, Wen-Qian Lin, Andrew D Maslow, Stavros G Memtsoudis, Dinis Reis Miranda, Pierre Moine, Thomas Ng, Domenico Paparella, V Marco Ranieri, Federica Scavonetto, Thomas Schilling, Gabriele Selmo, Paolo Severgnini, Juraj Sprung, Sugantha Sundar, Daniel Talmor, Tanja Treschan, Carmen Unzueta, Toby N Weingarten, Esther K Wolthuis, Hermann Wrigge, Marcelo B P Amato, Eduardo L V Costa, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J Schultz
Journal: The Lancet Respiratory Medicine (2016)
Nurturing Nature—Exploring the Possible Role of Epigenetics in Dyslipidemia
Authors: Marc S. Sabatine
Journal: JAMA Cardiology (2016)

Michael M. Mendelson, MD, ScM; Asya Lyass, PhD; Christopher J. O’Donnell, MD, MPH; Ralph B. D’Agostino Sr, PhD; Daniel Levy, MD
Antibodies against a secreted product of <i>Staphylococcus aureus</i> trigger phagocytic killing
Authors: Lena Thomer, Carla Emolo, Vilasack Thammavongsa, Hwan Keun Kim, Molly E. McAdow, Wenqi Yu, Matthew Kieffer, Olaf Schneewind, Dominique Missiakas
Journal: The Journal of Experimental Medicine (2016)

Host immunity against bacteria typically involves antibodies that recognize the microbial surface and promote phagocytic killing. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of lethal bloodstream infection; however, vaccines and antibody therapeutics targeting staphylococcal surface molecules have thus far failed to achieve clinical efficacy. S. aureus secretes coagulase (Coa), which activates host prothrombin and generates fibrin fibrils that protect the pathogen against phagocytosis by immune cells. Because of negative selection, the coding sequence for the prothrombin-binding D1-D2 domain is highly variable and does not elicit cross-protective immune responses. The R domain, tandem repeats of a 27-residue peptide that bind fibrinogen, is conserved at the C terminus of all Coa molecules, but its functional significance is not known. We show here that the R domain enables bloodstream infections by directing fibrinogen to the staphylococcal surface, generating a protective fibrin shield that inhibits phagocytosis. The fibrin shield can be marked with R-specific antibodies, which trigger phagocytic killing of staphylococci and protect mice against lethal bloodstream infections caused by a broad spectrum of MRSA isolates. These findings emphasize the critical role of coagulase in staphylococcal escape from opsonophagocytic killing and as a protective antigen for S. aureus vaccines.
Effects of human papillomavirus (HPV) and other potential risk factors on survival in patients with oropharyngeal cancer.
Authors: M. Knoedler, A. Zakarneh, U. Zimmermann, K. Woelke, O. Kaschke, U. Keilholz
Journal: Journal of Clinical Oncology (2011)

5577 Background: Oropharyngeal carcinomas are associated with HPV or with tobacco smoking and alcohol. HPV associated carcinomas arise most frequently in the tonsils and have a more favorable prognosis in contrast to tobacco smoking and alcohol induced carcinomas. Here we report on frequency and outcome of HPV associated oropharyngeal carcinomas (tonsils and base of tongue) in a Berlin cohort with high prevalence of smoking. Methods: Between 2005 and 2009 114 patients with oropharyngeal squamous cell carcinomas were diagnosed in a city hospital, 60 arising from tonsils and 54 from the base of tongue. Patients received surgery, chemoradiation or radiotherapy according to stage of disease. Complete follow-up information was obtained in fall of 2010. Histologic slides were retrieved and stained for p16 as indicator of HPV associated disease. Proportional-hazard models and log-rank tests were used to compare the risk of progression and death among patient subgroups. Results: Of all 114 patients, 81% were smokers and 64% tumors stained positive for p16 (tonsils 73%, base of tongue 54%). With a median follow-up of 28 months 31 patients had disease progression and 39 patients had died. 3-year PFS rates were 79% and 52% in patients with p16+ vs. p16- tumors (p= 0.001 by log-rank test) and 3-year OS rates were 78% and 39% in patients with p16+ vs. p16- tumors (p<0.001 by log-rank test). In cox regression analysis, only stage and p16 were independant prognostic factors. For PFS p16 had a hazard ratio (HR) of 0.44% (95% CI, 0.25 to 0.78) and also for OS a HR of 0.44% (95% CI, 0.24 to 0.78). Conclusions: Even in a European population with high prevalence of tobacco smoking, p16 positivity remains a strong favorable and independant risk factor, as has previously been shown in US cohorts with far lower smoking prevalence.
Polypharmacy in Elderly Cancer Patients
Authors: Kentaro Ogata, Hiroo Katsuya, Akihiko Shirahashi, Yousuke Ikari, Michio Masaki, Toshitaka Goto, Toshihiro Tanaka, Kenji Ishitsuka, Yasushi Takamatsu, Kazuo Tamura
Journal: Annals of Oncology (2014)
Abstract 12048: Subclinical Microalbuminuria is Associated With Poor Prognosis in Patients With Chronic Heart Failure With Preserved Renal Function-A Report From the CHART-2 Study-
Authors: Masanobu Miura, Yasuhiko Sakata, Satoshi Miyata, Kotaro Nochioka, Tsuyoshi Takada, Soichiro Tadaki, Jun Takahashi, Hiroaki Shimokawa
Journal: Circulation (2013)
Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening
Authors: Diana L. Miglioretti, Jane Lange, Jeroen J. van den Broek, Christoph I. Lee, Nicolien T. van Ravesteyn, Dominique Ritley, Karla Kerlikowske, Joshua J. Fenton, Joy Melnikow, Harry J. de Koning, Rebecca A. Hubbard
Journal: Annals of Internal Medicine (2016)

Background: Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. Objective: To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. Design: 2 simulation-modeling approaches. Setting: U.S. population. Patients: Women aged 40 to 74 years. Intervention: Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Measurements: Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100 000 women screened. Results: Annual screening of 100 000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100 000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100 000 women) than other women (113 cancer cases and 15 deaths per 100 000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Limitation: Life-years lost from radiation-induced breast cancer could not be estimated. Conclusion: Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Primary Funding Source: Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.
Effect of Duloxetine on Painful Chemotherapy-Induced Peripheral Neuropathy
Authors: Yasuo Hirayama, Takeshi Terui, Toshiro Kusakabe, Hiroto Horiguchi, Kaoru Ono, Kazuhiko Koike, Junji Kato, Kunihiko Ishitani
Journal: Annals of Oncology (2014)
Multiple Tumors in Female Germfree Inbred Albino Mice Exposed to Bedding Treated With Ethylene Oxide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J A REYNIERS, M R SACKSTEDER, L L ASHBURN
Journal: JNCI Journal of the National Cancer Institute (1964)

Germfree inbred albino mice were accidentally placed, for 150 days, on ground corncob bedding treated with ethylene oxide by the manufacturer. All the males died with massive hemorrhages in the thoracic and abdominal cavities, multiple hemorrhages in other sites, failure of the blood to clot, and jaundice. These effects confirm the results of Allen et al. [Nature (London) 193: 387–388, 1962], with conventional inbred mice. Few females were so affected. The first indication of a disturbance in the colony was failure to reproduce. The surviving, exposed females were held for observation. Over 90 percent of them, 400 to 900 days old, developed tumors of various kinds and in various sites. The ovaries were abnormal in almost all the animals examined. Graafian follicles and corpora lutea were rarely found. The history of the colony before exposure to ground corncob bedding treated with ethylene oxide, but in contact with nontreated ground corncobs from the same source, showed excellent reproduction and no tumors in either males or females up to 600 days of age. The blood-clotting time of these nonexposed mice and the blood picture were within the normal range for germfree animals.
Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials
Authors: Shing M. Lee, Daniel Backenroth, Ying Kuen Ken Cheung, Dawn L. Hershman, Diana Vulih, Barry Anderson, Percy Ivy, Lori Minasian
Journal: Journal of Clinical Oncology (2016)

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose.We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib.A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%.When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials.
Lactic Dehydrogenase Activity of Certain Tumors and Normal Tissues
Authors: Alton Meister
Journal: JNCI Journal of the National Cancer Institute (1950)

Lactic Dehydrogenase Activity of Certain Tumors and Normal Tissues Alton Meister Alton Meister National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 6, June 1950, Pages 1263–1271, https://doi.org/10.1093/jnci/10.6.1263 Published: 01 June 1950 Article history Received: 21 March 1950 Published: 01 June 1950
A longitudinal assessment of haloperidol doses and serum concentrations in Asian and Caucasian schizophrenic patients
Authors: K M Lin, R E Poland, I Nuccio, K Matsuda, N Hathuc, T P Su, P Fu
Journal: American Journal of Psychiatry (1989)

Over 3 months, 13 Caucasian and 16 Asian schizophrenic patients were sequentially treated with weight-adjusted fixed doses and clinically determined, variable doses of haloperidol. During the fixed-dose phase, Asians had a slightly higher mean serum haloperidol concentration and a significantly higher rating for extrapyramidal symptoms. During the variable-dose phase, the Asian patients' mean required dose was significantly lower, resulting in lower serum haloperidol concentrations at the first emergence of extrapyramidal symptoms and for optimal clinical response. These results indicate pharmacodynamic differences in therapeutic response but no significant difference in steady-state serum concentration between the two groups.
Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase
Authors: Yasuko Iwakiri
Journal: Clinical and Molecular Hepatology (2015)

The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions. Keywords: iNOS; NO; Liver sinusoidal endothelial cell; Hepatic stellate cell; Kupffer cell
Abstract 27: A Novel Variant Cell Cycle-related Kinase Provides Cardioprotection Upon Pressure Overload By Promoting Autophagy
Authors: Hongyu Qiu, Lo Lai
Journal: Circulation Research (2014)

Background: One approach to discovering novel targets for heart failure (HF) therapy is to determine which genes are down-regulated in HF. We found previously that cardiac cell cycle-related kinase (cCCRK), a novel variant of CCRK in heart, is down-regulated by 50% in failed heart vs control, and over-expression of the cCCRK decreases the susceptibility of cardiac myocytes to pro-apoptotic agents, indicating that cCCRK might be a potential target of HF. We tested here our hypothesis that cCCRK provides cardiaoprotection upon stress of pressure overload. Methods and Results: A transgenic (TG) mouse model with cardiac-specific over-expression of cCCRK was generated. Both wild type (WT) and TG mice were submitted to aortic banding for two weeks. In basal condition, no significant differences were found between TG and WT in left ventricular (LV) /body weight (3.5±0.3 in TG vs. 3.6±0.2 in WT) and contractility (LV ejection fraction (EF): 72.7±1 in TG vs 72.7±1 % in WT). After two weeks banding, EF was significantly impaired in the WT (62±2%, P&lt;0.05 vs sham), but maintained in the TG (71.1±2 %, P&lt;0.05 vs WT). Lung /tibial length ratio, an index of pulmonary congestion and heart failure was lower (p&lt;0.05) in banded heart of TG (9.9±1) vs WT (13.1±1). A cyclin-dependent kinase inhibitor p21, which is also an important regulator of autophagy, was significantly upregulated in TG by 5 folds vs WT (P&lt;0.05). Overexpression of cCCRK in rat neonatal cardiomyocyte (RNC) stimulated autophagy in a dose-dependent manner representing by the enhanced LC3-II (autophagy marker) (P&lt;0.05 vs β-gal). To test its effect in response to stress, glucose starvation was induced to in RNC. cCCRK induced an early response to cardiac stress via the activation of autophagy by increasing LC3-II at 0.5 hrs vs the control at 2 hrs after starvation. Conclusions: over-expression of cCCRK in heart provides protection against pressure overload via activation of autophagy signaling pathways.
Abstract 155: Mutations In ABCA8 Result In HDL Deficiency And Cholesterol Efflux Defects
Authors: Roshni Singaraja, Julian van Capelleveen, Kees Hovingh, Linhua Zhang, Geesje Dallinga-Thie, Ian Tietjen, Kenny Wong, John J Kastelein, Michael R Hayden
Journal: Circulation Research (2013)

The molecular basis of extreme HDL-C levels is incompletely understood. To identify mutations in novel putative HDL genes, we sequenced select genes in 80 unrelated individuals with extreme low HDLc (HDL %ile≤10th) and as controls, 120 individuals with high HDL (HDL %ile≥90th). We identified two variants in ABCA8 in subjects with low HDL-C levels. The E18-2T&gt;C mutation is located in a highly conserved region and gives rise to a disruption of a splice site. The G&gt;C variant occurs at a site conserved in vertebrates, at position 64425884 (build HG18), and results in Pro609Arg substitution. No ABCA8 mutations were identified in HHDL individuals. These represent the first mutations identified in ABCA8, which belongs to the family of ATP binding cassette transporters. Family expansion followed by genotyping identified additional mutation carriers and first degree relative controls in whom segregation analyses were performed. Compared with controls, mutation carriers showed a significant 32.6% decrease in plasma HDLc levels and decreased HDL percentiles (HDLc: controls = 1.23±0.26, mutation carriers = 0.83±0.37, mmol/L, p=0.0007; HDL%ile: controls = 41.8±21.2, mutation carriers = 17.3±19.2, p=0.004, n=23 controls and 12 carriers). No changes in LDLc, triglycerides or BMI were observed. Since mutations in ABCA8 reduce plasma HDLc levels, we assessed the role of ABCA8 in lipid efflux. Cholesterol efflux to lipid-free APOA-I was significantly reduced by 62.1% in fibroblasts from the proband with the E18-2 T&gt;C mutation. In comparison, fibroblasts from heterozygous ABCA1 mutation carriers showed a 30-60% decrease in efflux to APOA-I depending on mutation severity. Wild type and P609R ABCA8 cDNA clones were generated from human liver RNA. A significant ~200% increase in cholesterol efflux to lipid free APOA-I was observed with wild type ABCA8, further suggesting that ABCA8 is a lipid transporter. A significant 75% decrease in the efflux of cholesterol to lipid-free APOA-I (p=0.02) was observed with the mutant P609R ABCA8 protein compared to wild-type. We show here that ABCA8 is a cholesterol transporter, and that mutations in ABCA8 are a novel cause for reduced plasma HDLc levels in humans.
Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1
Authors: L Zanotti, R Angioni, B Calì, C Soldani, C Ploia, F Moalli, M Gargesha, G D'Amico, S Elliman, G Tedeschi, E Maffioli, A Negri, S Zacchigna, A Sarukhan, J V Stein, A Viola
Journal: Leukemia (2016)

Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases.
Adaptive Genetic Robustness of<i>Escherichia coli</i>Metabolic Fluxes
Authors: Wei-Chin Ho, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2016)

Genetic robustness refers to phenotypic invariance in the face of mutation and is a common characteristic of life, but its evolutionary origin is highly controversial. Genetic robustness could be an intrinsic property of biological systems, a result of direct natural selection, or a byproduct of selection for environmental robustness. To differentiate among these hypotheses, we analyze the metabolic network of Escherichia coli and comparable functional random networks. Treating the flux of each reaction as a trait and computationally predicting trait values upon mutations or environmental shifts, we discover that 1) genetic robustness is greater for the actual network than the random networks, 2) the genetic robustness of a trait increases with trait importance and this correlation is stronger in the actual network than in the random networks, and 3) the above result holds even after the control of environmental robustness. These findings demonstrate an adaptive origin of genetic robustness, consistent with the theoretical prediction that, under certain conditions, direct selection is sufficiently powerful to promote genetic robustness in cellular organisms.
Immunologic and Virologic Studies of a Non-producer Tumor Induced by Murine Sarcoma Virus (Harvey)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: McCoy, J. L., Ting, R. C., Morton, D. L., Law, L. W.
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Immunologic and Virologic Studies of a Non-producer Tumor Induced by Murine Sarcoma Virus (Harvey) Get access J. L. McCoy, J. L. McCoy Bionetics Research Laboratory and National Cancer Institute,7Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. C. Ting, R. C. Ting Bionetics Research Laboratory and National Cancer Institute,7Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar D. L. Morton, D. L. Morton Bionetics Research Laboratory and National Cancer Institute,7Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar L. W. Law L. W. Law Bionetics Research Laboratory and National Cancer Institute,7Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 2, February 1972, Pages 383–391, https://doi.org/10.1093/jnci/48.2.383 Published: 01 February 1972 Article history Received: 01 July 1971 Accepted: 20 October 1971 Published: 01 February 1972
Frontal Fibrosing Alopecia Severity Index ( <scp>FFASI</scp> ): a validated scoring system for assessing frontal fibrosing alopecia
Authors: S. Holmes, T. Ryan, D. Young, M. Harries
Journal: British Journal of Dermatology (2016)

The incidence of frontal fibrosing alopecia (FFA) appears to be increasing(1-6) and response to treatment has been largely disappointing(1-3) . However, assessment of treatment interventions is confounded by slow disease progression and lack of robust means of assessing disease severity and activity. To address the latter, we have developed a validated clinical scoring system - the FFA severity index (FFASI), which provides a standardised framework for FFA assessment and patient.