tbuckley/cabot-search huggingface dataset:
The Epidemiology of Sepsis in the United States from 1979 through 2000
Authors: Greg S. Martin, David M. Mannino, Stephanie Eaton, Marc Moss
Journal: New England Journal of Medicine (2003)

Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of patients, and the incidence and outcome.
CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma
Authors: Jian Hong, Kaishun Hu, Yunfei Yuan, Yi Sang, Qiangui Bu, Guihua Chen, Longjun Yang, Binkui Li, Pinzhu Huang, Dongtai Chen, Yi Liang, Ruhua Zhang, Jingxuan Pan, Yi-Xin Zeng, Tiebang Kang
Journal: Journal of Clinical Investigation (2012)

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies resistant to current chemotherapies or radiotherapies, which makes it urgent to identify new therapeutic targets for HCC. In this study, we found that checkpoint kinase 1 (CHK1) was frequently overexpressed and correlated with poor clinical outcome in patients with HCC. We further showed that the CHK1 inhibitor GÖ6976 was capable of sensitizing HCC cells to cisplatin, indicating that CHK1 may have oncogenic function in HCC. We found that CHK1 phosphorylated the tumor suppressor spleen tyrosine kinase (L) (SYK[L]) and identified the phosphorylation site at Ser295. Furthermore, CHK1 phosphorylation of SYK(L) promoted its subsequent proteasomal degradation. Expression of a nonphosphorylated mutant of SYK(L) was more efficient at suppressing proliferation, colony formation, mobility, and tumor growth in HCC lines. Importantly, a strong inverse correlation between the expression levels of CHK1 and SYK(L) was observed in patients with HCC. Collectively, our data demonstrate that SYK(L) is a substrate of CHK1 in tumor cells and suggest that targeting the CHK1/SYK(L) pathway may be a promising strategy for treating HCC.
A rat model of progressive chronic glomerular sclerosis
Authors: R A Stahl, F Thaiss, U Wenzel, W Schoeppe, U Helmchen
Journal: Journal of the American Society of Nephrology (1992)

In order to evaluate a possible role of thromboxane A2 (TxA2) in the pathophysiology of chronic glomerular disease, we studied the effect of a 12-wk combined treatment with the thromboxane receptor blocker Daltroban (D) and the thromboxane synthesis inhibitor UK 38485 (UK) on glomerular function and morphology in a rat model of chronic progressive glomerular injury. The glomerular lesion was induced in unilaterally nephrectomized rats by the repeated i.v. injection of an antibody directed against mesangial cells. Control rats were uninephrectomized. Three months after the first antibody injection before D and UK treatment, albuminuria (35.8 +/- 3.6 mg/24 h) and glomerular TxB2 formation (146 +/- 20 pg/mg of protein/min) were significantly higher compared with control values (albuminuria, 14.3 +/- 3.5 mg/24 h; TxB2, 59 +/- 16 pg/mg/min). Six months after antibody, albuminuria in nephritic rats had increased to 135 +/- 17 mg/24 h. In nephritic rats treated with D plus UK, albuminuria (44 +/- 12 mg/24 h), however, was significantly (P less than 0.001) inhibited. Quantitative morphological analysis (glomerular damage index) 6 months after antibody revealed significantly (P less than 0.001) increased glomerular lesions in nephritic rats (0.353 +/- 0.095) compared with that in uninephrectomized controls (0.045 +/- 0.014). The treatment of rats with D and UK significantly (P less than 0.001) reduced the glomerular damage index (0.101 +/- 0.004) in nephritic rats. D plus UK treatment reduced glomerular TxB2 formation but increased prostaglandin E2 and 6-keto prostaglandin F1 alpha release by isolated glomeruli. This study demonstrates that interventional treatment with D and UK ameliorates albuminuria and glomerular morphological lesions in a rat model of immunologically induced progressive glomerular injury.
Maternal–Fetal Microtransfusions and HIV-1 Mother-to-Child Transmission in Malawi
Authors: Jesse J Kwiek, Victor Mwapasa, Danny A Milner, Alisa P Alker, William C Miller, Eyob Tadesse, Malcolm E Molyneux, Stephen J Rogerson, Steven R Meshnick
Journal: PLoS Medicine (2005)

Background Between 25% and 35% of infants born to HIV-infected mothers become HIV-1 infected. One potential route of mother-to-child transmission (MTCT) could be through a breakdown in the placental barrier (i.e., maternal–fetal microtransfusions). Methods and Findings Placental alkaline phosphatase (PLAP) is a 130-kD maternal enzyme that cannot cross the intact placental barrier. We measured PLAP activity in umbilical vein serum as an indicator of maternal–fetal microtransfusion, and related this to the risk of HIV-1 MTCT. A case-cohort study was conducted of 149 women randomly selected from a cohort of HIV-1-infected pregnant Malawians; these women served as a reference group for 36 cases of in utero MTCT and 43 cases of intrapartum (IP) MTCT. Cord PLAP activity was measured with an immunocatalytic assay. Infant HIV status was determined by real-time PCR. The association between cord PLAP activity and HIV-1 MTCT was measured with logistic regression using generalized estimating equations. Among vaginal deliveries, PLAP was associated with IP MTCT (risk ratio, 2.25 per log10 ng/ml PLAP; 95% confidence interval, 0.95–5.32) but not in utero MTCT. In a multivariable model adjusted for HIV-1 RNA load, chorioamnionitis, and self-reported fever, the risk of IP MTCT almost tripled for every log10 increase in cord PLAP activity (risk ratio, 2.87; 95% confidence interval, 1.05–7.83). Conclusion These results suggest that during vaginal deliveries, placental microtransfusions are a risk factor for IP HIV-1 MTCT. Future studies are needed to identify factors that increase the risk for microtransfusions in order to prevent IP HIV-1 MTCT.
Life-table analysis of etanercept with or without methotrexate in patients with psoriatic arthritis
Authors: A Spadaro, F Ceccarelli, R Scrivo, G Valesini
Journal: Annals of the Rheumatic Diseases (2008)

The recent analysis of data included in the Stockholm TNFα Follow- Up (STURE) registry showed that the concomitant use of methotrexate (MTX) with etanercept (ETN), adalimumab or infliximab was associated with long-term drug survival of anti-tumour necrosis factor (TNF) agents in patients with psoriatic arthritis (PsA).1 The positive effect of MTX was primarily linked to fewer drop-outs due to adverse events.1 This analysis did not consider each anti-TNF drug subgroup. For this reason we determined the cumulative probability of taking ETN with or without MTX in a large cohort of patients.

We prospectively studied 82 patients, admitted to our rheumatological unit since 2001, affected by PsA, classified …
Supervenience and qualia
Authors: Ken Mogi
Journal: Behavioral and Brain Sciences (1999)

The privileged position of neural activity in biological neuroscience might be justified on the grounds of the nonlinear and all-or-none character of neural firing. To justify the neuron doctrine in cognitive neuroscience and make it both plausible and radical, we must consider the supervenience of elementary mental properties such as qualia on neural activity.
A novel type 2A von Willebrand factor mutation located at the last nucleotide of exon 26 (3538G&amp;gt;A) causes skipping of 2 nonadjacent exons
Authors: Paula D. James, Lee A. O'Brien, Carol A. Hegadorn, Colleen R. P. Notley, Gary D. Sinclair, Christine Hough, Man-Chiu Poon, David Lillicrap
Journal: Blood (2004)
Retinopathy Predicts Cardiovascular Mortality in Type 2 Diabetic Men and Women
Authors: Auni Juutilainen, Seppo Lehto, Tapani Rönnemaa, Kalevi Pyörälä, Markku Laakso
Journal: Diabetes Care (2007)

To investigate the association of retinopathy with the risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in type 2 diabetic subjects in a population-based 18-year follow-up study with particular emphasis on sex differences.Our study cohort comprised 425 Finnish type 2 diabetic men and 399 type 2 diabetic women who were free of CVD at baseline. The findings were classified based on standardized clinical ophthalmoscopy to categories of no retinopathy, background retinopathy, and proliferative retinopathy. The study end points were all-cause, CVD, and CHD mortality.Adjusted Cox model hazard ratios (95% CIs) of all-cause, CVD, and CHD mortality in men were 1.34 (0.98-1.83), 1.30 (0.86-1.96), and 1.18 (0.74-1.89), respectively, for background retinopathy and 3.05 (1.70-5.45), 3.32 (1.61-6.78), and 2.54 (1.07-6.04), respectively, for proliferative retinopathy and in women 1.61 (1.17-2.22), 1.71 (1.17-2.51), and 1.79 (1.13-2.85), respectively, for background retinopathy and 2.92 (1.41-6.06), 3.17 (1.38-7.30), and 4.98 (2.06-12.06), respectively, for proliferative retinopathy.Proliferative retinopathy in both sexes and background retinopathy in women predicted all-cause, CVD, and CHD death. These associations were independent of current smoking, hypertension, total cholesterol, HDL cholesterol, glycemic control of diabetes, duration of diabetes, and proteinuria. This suggests the presence of common background pathways for diabetic microvascular and macrovascular disease other than those included in the conventional risk assessment of CVD. The sex difference observed in the association of background retinopathy with macrovascular disease warrants closer examination.
Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial
Authors: S. Boeck, K. Weigang-Köhler, M. Fuchs, E. Kettner, D. Quietzsch, J. Trojan, O. Stötzer, S. Zeuzem, F. Lordick, C-H. Köhne, H. Kröning, T. Steinmetz, H. Depenbrock, V. Heinemann
Journal: Annals of Oncology (2007)
Pancreatic function and the absorption of fat, iron, vitamin B12, and calcium after total gastrectomy for gastric cancer.
Authors: K Fischermann, S Harly, H Worning, A Zacho
Journal: Gut (1967)

Twelve patients who had had a total gastrectomy have been carefully studied.No difference was found in those patients who had had either a Roux or an interposition type of operation.
Small Heat Shock Protein 20 Interacts With Protein Phosphatase-1 and Enhances Sarcoplasmic Reticulum Calcium Cycling
Authors: Jiang Qian, Elizabeth Vafiadaki, Stela M. Florea, Vivek P. Singh, Weizhong Song, Chi Kung Lam, Yigang Wang, Qunying Yuan, Tracy J. Pritchard, Wenfeng Cai, Kobra Haghighi, Patricia Rodriguez, Hong-Sheng Wang, Despina Sanoudou, Guo-Chang Fan, Evangelia G. Kranias
Journal: Circulation Research (2011)

Background: Heat shock proteins (Hsp) are known to enhance cell survival under various stress conditions. In the heart, the small Hsp20 has emerged as a key mediator of protection against apoptosis, remodeling, and ischemia/reperfusion injury. Moreover, Hsp20 has been implicated in modulation of cardiac contractility ex vivo. The objective of this study was to determine the in vivo role of Hsp20 in the heart and the mechanisms underlying its regulatory effects in calcium (Ca) cycling. Methods and Results: Hsp20 overexpression in intact animals resulted in significant enhancement of cardiac function, coupled with augmented Ca cycling and sarcoplasmic reticulum Ca load in isolated cardiomyocytes. This was associated with specific increases in phosphorylation of phospholamban (PLN) at both Ser16 and Thr17, relieving its inhibition of the apparent Ca affinity of SERCA2a. Accordingly, the inotropic effects of Hsp20 were abrogated in cardiomyocytes expressing nonphosphorylatable PLN (S16A/T17A). Interestingly, the activity of type 1 protein phosphatase (PP1), a known regulator of PLN signaling, was significantly reduced by Hsp20 overexpression, suggesting that the Hsp20 stimulatory effects are partially mediated through the PP1–PLN axis. This hypothesis was supported by cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, which revealed an association between Hsp20, PP1, and PLN. Furthermore, recombinant protein studies confirmed a physical interaction between AA 73 to 160 in Hsp20 and AA 163 to 330 in PP1. Conclusions: Hsp20 is a novel regulator of sarcoplasmic reticulum Ca cycling by targeting the PP1–PLN axis. These findings, coupled with the well-recognized cardioprotective role of Hsp20, suggest a dual benefit of targeting Hsp20 in heart disease.
Autotransporters and virulence of enteroaggregative<i>E. coli</i>
Authors: Fernando Navarro-Garcia, Waldir P. Elias
Journal: Gut Microbes (2011)

Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen associated with acute and persistent diarrhea in children and adults. EAEC strains are very heterogeneous and the pathogenesis of EAEC diarrhea is complex and not completely understood. Studies have suggested three major features of EAEC pathogenesis: abundant adherence to the intestinal mucosa, elaboration of enterotoxins and cytotoxins, and induction of mucosal inflammation. Here, we discuss the role of the virulence factors involved in these three major features, focusing in the EAEC adhesion including fimbrial and afimbrial factors, EAEC toxins and autotransporter proteins, such as Pet (plasmid encoded toxin) and Pic (protein involved in colonization); both proteins play a role in two EAEC pathogenic features: cytotoxicity and mucosal colonization, including the bacterium-mucus biofilm. Finally we discuss relevant factors involved in the inflammatory process induce by EAEC, such as flagellin, fimbria and regulator factors (AggR). Interestingly, all these factors are not present in all EAEC strain, contributing to EAEC heterogeneity.
A majority of parents of children with peanut allergy fear using the epinephrine auto-injector
Authors: L. Chad, M. Ben-Shoshan, Y. Asai, S. Cherkaoui, R. Alizadehfar, Y. St-Pierre, L. Harada, M. Allen, A. Clarke
Journal: Allergy (2013)

Prompt epinephrine administration is crucial in managing anaphylaxis, but epinephrine auto-injectors (EAIs) are underutilized by patients and their families. Children with peanut allergy were recruited from the Allergy Clinics at the Montreal Children's Hospital, food allergy advocacy organizations and organizations providing products to allergic individuals. Parents of children who had been prescribed an EAI were queried on whether they were fearful of using it and on factors that may contribute to fear. A majority of parents (672/1209 = 56%) expressed fear regarding the use of the EAI. Parents attributed the fear to hurting the child, using the EAI incorrectly or a bad outcome. Parents whose child had longer disease duration or a severe reaction and parents who were satisfied with the EAI training or found it easy to use were less likely to be afraid. Families may benefit from simulation training and more education on the recognition and management of anaphylaxis.
Unstressing intemperate models: how cold stress undermines mouse modeling
Authors: Christopher L. Karp
Journal: The Journal of Experimental Medicine (2012)

Mus musculus enjoys pride of place at the center of contemporary biomedical research. Despite being the current model system of choice for in vivo mechanistic analysis, mice have clear limitations. The literature is littered with examples of therapeutic approaches that showed promise in mouse models but failed in clinical trials. More generally, mice often provide poor mimics of the human diseases being modeled. Available data suggest that the cold stress to which laboratory mice are ubiquitously subjected profoundly affects mouse physiology in ways that impair the modeling of human homeostasis and disease. Experimental attention to this key, albeit largely ignored, environmental variable is likely to have a broad transformative effect on biomedical research.
Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized Placebo-Controlled Trial
Authors: Jun J. Mao, Marjorie A. Bowman, Sharon X. Xie, Deborah Bruner, Angela DeMichele, John T. Farrar
Journal: Journal of Clinical Oncology (2015)

Hot flashes are a common and debilitating symptom among survivors of breast cancer. This study aimed at evaluating the effects of electroacupuncture (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer, with a specific focus on the placebo and nocebo effects.We conducted a randomized controlled trial involving 120 survivors of breast cancer experiencing bothersome hot flashes twice per day or greater. Participants were randomly assigned to receive 8 weeks of EA or GP once per day with validated placebo controls (sham acupuncture [SA] or placebo pills [PPs]). The primary end point was change in the hot flash composite score (HFCS) between SA and PP at week 8, with secondary end points including group comparisons and additional evaluation at week 24 for durability of treatment effects.By week 8, SA produced significantly greater reduction in HFCS than did PP (-2.39; 95% CI, -4.60 to -0.17). Among all treatment groups, the mean reduction in HFCS was greatest in the EA group, followed by SA, GP, and PP (-7.4 v -5.9 v -5.2 v -3.4; P = < .001). The pill groups had more treatment-related adverse events than did the acupuncture groups: GP (39.3%), PP (20.0%), EA (16.7%), and SA (3.1%), with P = .005. By week 24, HFCS reduction was greatest in the EA group, followed by SA, PP, and GP (-8.5 v -6.1 v -4.6 v -2.8; P = .002).Acupuncture produced larger placebo and smaller nocebo effects than did pills for the treatment of hot flashes. EA may be more effective than GP, with fewer adverse effects for managing hot flashes among breast cancer survivors; however, these preliminary findings need to be confirmed in larger randomized controlled trials with long-term follow-up.
Involvement of Egr-1/RelA Synergy in Distinguishing T Cell Activation from Tumor Necrosis Factor-α–induced <i>NF-κB1</i> Transcription
Authors: Patricia C. Cogswell, Marty W. Mayo, Albert S. Baldwin
Journal: The Journal of Experimental Medicine (1997)

NF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha, despite the fact that both stimuli activate NF-kappa B. Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-kappa B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression.
Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis
Authors: Sophie A Jamal, Ben Vandermeer, Paolo Raggi, David C Mendelssohn, Trish Chatterley, Marlene Dorgan, Charmaine E Lok, David Fitchett, Ross T Tsuyuki
Journal: The Lancet (2013)
Primary Importance of Zwitterionic Over Anionic Phospholipids in the Surface-active Function of Calf Lung Surfactant Extract
Authors: ZHENGDONG WANG, OKYANUS GUREL, SUSAN WEINBACH, ROBERT H. NOTTER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The relative contributions of zwitterionic and anionic phospholipids to the surface-active function of calf lung surfactant extract (CLSE) were assessed by measurements of surface properties in vitro and pressure-volume (P-V) mechanics in excised rat lungs in situ. Surface activity and mechanical effects were compared for chromatographically purified CLSE subfractions containing the complete mix of phospholipids (PPL) or modified phospholipids depleted in anionic components (mPPL), alone or combined with 1.3% (by weight) of hydrophobic surfactant proteins (SP-B and SP-C). Surface pressure-time ( π -t) adsorption isotherms at 37 ° C were very similar for dispersions of PPL and mPPL in a Teflon dish with a stirred subphase to minimize diffusion resistance. Combination of either PPL or mPPL with hydrophobic SP substantially improved adsorption, but mixtures of PPL : SP and mPPL : SP had only small differences in π -t isotherms and reached the same final equilibrium π of ∼ 47 mN/m achieved by CLSE. Surface pressure-area ( π -A) isotherms and maximum surface pressures were also very similar for spread films of PPL versus mPPL and PPL : SP versus mPPL : SP on the Wilhelmy balance (23 ° C and 37 ° C). Respreading based on π -A isotherm area calculations was slightly better in surface-excess films of PPL versus mPPL and PPL : SP versus mPPL : SP, but differences were minor and were smaller at 37 ° C than at 23 ° C. Overall dynamic surface activity in oscillating bubble studies was not significantly different for PPL versus mPPL or for PPL : SP versus mPPL : SP, and the latter two mixtures both reached minimum surface tensions < 1 mN/m (37 ° C, 20 cycles/min, 0.5 mM phospholipid). Dispersions of PPL : SP, mPPL : SP, and CLSE were also not significantly different in improving P-V mechanics almost to normal when instilled in lavaged, excised rat lungs at 37 ° C (30 mg/2.5 ml saline). These data suggest that zwitterionic phospholipids have a major role over anionic phospholipids in interacting with hydrophobic SP in the adsorption, dynamic surface tension lowering, film respreading, and pulmonary mechanical activity of the hydrophobic components of calf lung surfactant in CLSE.