tbuckley/cabot-search huggingface dataset:
The Immune Response to Pneumococcal Proteins during Experimental Human Carriage
Authors: Tera L. McCool, Thomas R. Cate, Gregory Moy, Jeffrey N. Weiser
Journal: The Journal of Experimental Medicine (2002)

Colonization of the nasopharynx is the initial step in all infections caused by Streptococcus pneumoniae. The antibody response to carriage was examined in an experimental model of human colonization in healthy adults. Asymptomatic colonization was detected in 6/14 subjects and continued for up to 122 d. Susceptibility to carriage did not correlate with total serum immunoglobulin (Ig)G to the homotypic capsular polysaccharide. All of the colonized subjects, in contrast, developed a serum IgG and secretory IgA response to a 22 kD protein, whereas 7 of 8 subjects who did not become colonized had preexisting antibody to this protein. Analysis of the 22 kD protein identified it as the NH2-terminal region of pneumococcal surface protein A (PspA). Our findings provide evidence for the role of antibody to this protein fragment in preventing pneumococcal carriage by humans.
Comparative transcriptomics among floral organs of the basal eudicot Eschscholzia californica as reference for floral evolutionary developmental studies
Authors: Laura M Zahn, Xuan Ma, Naomi S Altman, Qing Zhang, P Kerr Wall, Donglan Tian, Cynthia J Gibas, Raad Gharaibeh, James H Leebens-Mack, Claude W dePamphilis, Hong Ma
Journal: Genome biology (2010)

Molecular genetic studies of floral development have concentrated on several core eudicots and grasses (monocots), which have canalized floral forms. Basal eudicots possess a wider range of floral morphologies than the core eudicots and grasses and can serve as an evolutionary link between core eudicots and monocots, and provide a reference for studies of other basal angiosperms. Recent advances in genomics have enabled researchers to profile gene activities during floral development, primarily in the eudicot Arabidopsis thaliana and the monocots rice and maize. However, our understanding of floral developmental processes among the basal eudicots remains limited. Using a recently generated expressed sequence tag (EST) set, we have designed an oligonucleotide microarray for the basal eudicot Eschscholzia californica (California poppy). We performed microarray experiments with an interwoven-loop design in order to characterize the E. californica floral transcriptome and to identify differentially expressed genes in flower buds with pre-meiotic and meiotic cells, four floral organs at pre-anthesis stages (sepals, petals, stamens and carpels), developing fruits, and leaves. Our results provide a foundation for comparative gene expression studies between eudicots and basal angiosperms. We identified whorl-specific gene expression patterns in E. californica and examined the floral expression of several gene families. Interestingly, most E. californica homologs of Arabidopsis genes important for flower development, except for genes encoding MADS-box transcription factors, show different expression patterns between the two species. Our comparative transcriptomics study highlights the unique evolutionary position of E. californica compared with basal angiosperms and core eudicots.
Widespread body pain and mortality: prospective population based study Commentary: An interesting finding, but what does it
Authors: G. J Macfarlane, J. McBeth, A. J Silman, I K Crombie
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine whether there is excess mortality in groups of people who report widespread body pain, and if so to establish the nature and extent of any excess. <b>Design:</b> Prospective follow up study over eight years. Mortality rate ratios were adjusted for age group, sex, and study location. <b>Setting:</b> North west England. <b>Participants:</b> 6569 people who took part in two pain surveys during 1991-2. <b>Main outcome measures:</b> Pain status at baseline and subsequent mortality. <b>Results:</b> 1005 (15%) participants had widespread pain, 3176 (48%) had regional pain, and 2388 (36%) had no pain. During follow up mortality was higher in people with regional pain (mortality rate ratio 1.21, 95% confidence interval 1.01 to 1.44) and widespread pain (1.31, 1.05 to 1.65) than in those who reported no pain. The excess mortality among people with regional and widespread pain was almost entirely related to deaths from cancer (1.55 (1.09 to 2.19) for regional pain and 2.07 (1.37 to 3.13) for widespread pain). The excess cancer mortality remained after exclusion of people in whom cancer had been diagnosed before the original survey and after adjustment for potential confounding factors. There were also more deaths from causes other than disease (for example, accidents, suicide, violence) among people with widespread pain (5.21, 0.94 to 28.78). <b>Conclusion:</b> There is an intriguing association between the report of widespread pain and subsequent death from cancer in the medium and long term. This may have implications for the long term follow up of patients with "unexplained" widespread pain symptoms, such as those with fibromyalgia. <h3>What is already known on this topic</h3> Widespread body pain, the cardinal symptom of fibromyalgia, is common An organic basis for symptoms is found in only a small proportion of people Treatment is difficult, and studies with short term follow up have shown that symptoms commonly persist <h3>What this study adds</h3> This was the first study with long term follow up of people with widespread pain in the community These people experience an increased mortality and the excess is principally related to deaths from cancer
Silibinin Sensitizes Human Glioma Cells to TRAIL-Mediated Apoptosis via DR5 Up-regulation and Down-regulation of c-FLIP and Survivin
Authors: Yong-gyu Son, Eun Hee Kim, Jin Yeop Kim, Seung U. Kim, Taeg Kyu Kwon, A-Rum Yoon, Chae-Ok Yun, Kyeong Sook Choi
Journal: Cancer Research (2007)

Abstract Silibinin, a flavonoid isolated from Silybum marianum, has been reported to have cancer chemopreventive and therapeutic effects. Here, we show that treatment with subtoxic doses of silibinin in combination with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, but not in human astrocytes, suggesting that this combined treatment may offer an attractive strategy for safely treating gliomas. Although the proteolytic processing of procaspase-3 by TRAIL was partially blocked in glioma cells, cotreatment with silibinin efficiently recovered TRAIL-induced caspase activation in these cells. Silibinin treatment up-regulated DR5, a death receptor of TRAIL, in a transcription factor CHOP-dependent manner. Furthermore, treatment with silibinin down-regulated the protein levels of the antiapoptotic proteins FLIPL, FLIPS, and survivin through proteasome-mediated degradation. Taken together, our results show that the activity of silibinin to modulate multiple components in the death receptor–mediated apoptotic pathway is responsible for its ability to recover TRAIL sensitivity in TRAIL-resistant glioma cells. [Cancer Res 2007;67(17):8274–84]
Molecular Classification of Malignant Pleural Mesothelioma: Identification of a Poor Prognosis Subgroup Linked to the Epithelial-to-Mesenchymal Transition
Authors: Aurélien de Reyniès, Marie-Claude Jaurand, Annie Renier, Gabrielle Couchy, Ilir Hysi, Nabila Elarouci, Françoise Galateau-Sallé, Marie-Christine Copin, Paul Hofman, Aurélie Cazes, Pascal Andujar, Sandrine Imbeaud, Fabien Petel, Jean-Claude Pairon, Francoise Le Pimpec-Barthes, Jessica Zucman-Rossi, Didier Jean
Journal: Clinical Cancer Research (2014)

Despite research efforts to develop more effective diagnostic and therapeutic approaches, malignant pleural mesothelioma (MPM) prognosis remains poor. The assessment of tumor response to therapy can be improved by a deeper phenotypical classification of the tumor, with emphasis on its clinico-biological heterogeneity. The identification of molecular profiles is a powerful approach to better define MPM subclasses and targeted therapies.Molecular subclasses were defined by transcriptomic microarray on 38 primary MPM cultures. A three-gene predictor, identified by quantitative reverse transcription PCR, was used to classify an independent series of 108 frozen tumor samples. Gene mutations were determined in BAP1, CDKN2A, CDKN2B, NF2, and TP53. Epithelial-to-mesenchymal transition (EMT) markers were studied at the mRNA and protein levels.Unsupervised hierarchical clustering on transcriptomic data defined two robust MPM subgroups (C1 and C2), closely related to prognosis and partly to histologic subtypes. All sarcomatoid/desmoplastic MPM were included in the C2 subgroup. Epithelioid MPM were found in both subgroups, with a worse survival prognosis in the C2 subgroup. This classification and its association with histologic subtypes and survival were validated in our independent series using the three-gene predictor. Similar subgroups were found after classification of other MPM series from transcriptomic public datasets. C1 subgroup exhibited more frequent BAP1 alterations. Pathway analysis revealed that EMT was differentially regulated between MPM subgroups. C2 subgroup is characterized by a mesenchymal phenotype.A robust classification of MPM that defines two subgroups of epithelioid MPM, characterized by different molecular profiles, gene alterations, and survival outcomes, was established.
Fulminant Hepatic Failure Caused by Acute Fatty Liver of Pregnancy Treated by Orthotopic Liver Transplantation
Authors: Samuel A. Ockner, Elizabeth M. Brunt, Steven M. Cohn, Elaine S. Krul, Douglas W. Hanto, Marion G. Peters
Journal: Hepatology (1990)

A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.
An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas
Authors: M. Agulnik, J.L. Yarber, S.H. Okuno, M. von Mehren, B.D. Jovanovic, B.E. Brockstein, A.M. Evens, R.S. Benjamin
Journal: Annals of Oncology (2012)

To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas.In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15 mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days.Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable.Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.
Risk of hepatitis B infections in Olympic wrestling
Authors: S Bereket-Yücel
Journal: British Journal of Sports Medicine (2007)

Objective: First, to investigate the prevalence of the hepatitis B virus (HBV) and occult HBV infection (OC-HBV) in Turkish Olympic wrestlers. Second, to examine the relationship between HBV DNA values in sweat and blood. Methods: A total of 70 male Olympic wrestlers were recruited as the study sample. Results: As a result of the standard monoclonal antibody based hepatitis B surface antigen (HBsAg) detection, none of the Olympic wrestlers carried HBsAg in this study. On the other hand, according to real time PCR for serum HBV DNA detection in this study, 9 (13%) of the wrestlers had OC-HBV infection. Eight (11%) of the participants had HBV DNA in their sweat. In addition, there was a significant relationship between HBV DNA values in the blood and sweat of the wrestlers ( r = 0.52, p&lt;0.01). Conclusions: In addition to bleeding wounds and mucous membranes, sweating may be another way of transmitting HBV infections in contact sports. An HBV test should be done and each wrestler should be vaccinated at the start of his career.
Running in new and worn shoes: a comparison of three types of cushioning footwear
Authors: P W Kong, N G Candelaria, D R Smith
Journal: British Journal of Sports Medicine (2008)

Objectives: In this study, the effect of shoe degradation on running biomechanics by comparing the kinetics and kinematics of running in new and worn shoes was investigated. Three types of footwear using different cushioning technologies were compared. Design: Longitudinal study. Setting: Pre- and post-tests on overground running at 4.5 m s −1 on a 20-m laboratory runway; performance measured using a force platform and a motion capture system. Participants: 24 runners (14 men and 10 women) Interventions: 200 miles of road running in the same pair of shoes. Within-group factor: shoe condition (new/worn); between-group factor: footwear type (air/gel/spring). Main outcome measurements: Stance time was calculated from force data. External loads were measured by maximum vertical force and loading rate. Kinematic changes were indicated by sagittal plane angles of the torso, hip, knee and ankle at critical events during the stance phase. Results: Stance time increased (p = 0.035) in worn shoes. The torso displayed less maximum forward lean (p&lt;0.001) and less forward lean at toe-off (p&lt;0.001), while the ankle displayed reduced maximum dorsiflexion (p = 0.013) and increased plantar flexion at toe-off (p&lt;0.001) in worn shoes. No changes in the hip and knee angles. No between-group difference among the three footwear groups or condition by type interaction was found in any measured variables. Conclusions: As shoe cushioning capability decreases, runners modify their patterns to maintain constant external loads. The adaptation strategies to shoe degradation were unaffected by different cushioning technologies, suggesting runners should choose shoes for reasons other than cushioning technology.
Central nervous system stimulants and sport practice
Authors: L Avois, N Robinson, C Saudan, N Baume, P Mangin, M Saugy
Journal: British Journal of Sports Medicine (2006)

Background and objectives: Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. Methods: Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. Results: CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti-doping laboratories statistics and the media, and their potentially serious adverse effects. Conclusions: Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced.
Pay-for-Performance and Accountability: Related Themes in Improving Health Care
Authors: John W. Rowe
Journal: Annals of Internal Medicine (2006)

Value-based purchasing, or pay-for-performance, is a major emerging theme in U.S. health care. Forces enhancing adoption of pay-for-performance programs include continued increases in medical costs beyond overall economic growth, a body of evidence that the quality of health care provided to patients is not directly related to the volume of services received, increasing evidence to serve as a basis for the development of standards against which to measure clinical performance, and increasing acceptance by physician organizations and individual practitioners of the rationale underlying these efforts. In this context, employers, government payers, and health plans are establishing a wide variety of pay-for-performance programs. This article reviews the critical design features of such efforts, describes the current types of programs on offer, and comments on the implications of this emerging movement for the future of health care in the United States.
Consider non-invasive follow-up and malabsorption in old age
Authors: J. Schneede
Journal: BMJ (2010)

Hudson describes the classic clinical signs of vitamin B-12 deficiency in an elderly patient and recommends traditional diagnostic procedures such as measuring vitamin B-12 values and determining antibodies against intrinsic factor and parietal cells.1 However, old age itself poses a dilemma for further diagnostic strategies.2 Of course, invasive procedures such as gastroscopy and bone …
Peroxisome proliferator-activated receptor ? transcriptional regulation is involved in platelet-derived growth factor-induced proliferation of human hepatic stellate cells
Authors: Andrea Galli, David Crabb, Donna Price, Elisabetta Ceni, Renata Salzano, Calogero Surrenti, Alessandro Casini
Journal: Hepatology (2000)

During liver injury, hepatic stellate cells (HSC) acquire a myofibroblast-like phenotype associated with reduction of lipid droplets, increased collagen synthesis, and proliferation. Peroxisome proliferator-activated receptor γ (PPARγ) regulates adipocyte differentiation and controls gene transcription in response to various activators including prostanoids and antidiabetic thiazolidinediones. We explored whether the presence of PPARγ and its transcriptional activity were involved in control of HSC proliferation in vitro . PPARγ ligands, 15-deoxy-△ 12 14 prostaglandin J 2 (15d-PGJ 2 ) and ciglitizone, significantly decrease platelet-derived growth factor (PDGF)-induced proliferation in activated human HSC and inhibit α smooth muscle actin (α-SMA) expression during HSC transdifferentiation. Treatment with 9-cis retinoic acid (9-cisRA) and LG268, ligands of the heterodimerization partner retinoic X receptor (RXR), had a negligible effect in PDGF-treated cells but caused a further reduction of proliferation when used in combination with ciglitizone. Transfection experiments with a reporter gene consisting of 3 copies of a PPAR response element (peroxisome proliferator response element [PPRE] 3 -tk-luciferase) showed a progressive reduction of PPAR transcriptional activity during plastic-induced HSC transdifferentiation. Cotransfection with human PPARγ expression vector restored the PPRE 3 -tk-luciferase reporter expression and the increased level of the receptor in activated HSC-inhibited cell proliferation in a dose-dependent manner. Incubation of human PPARγ-cotransfected HSC with PDGF strongly inhibited luciferase activity and this effect was blocked by the inhibition of the mitogen-activated protein (MAP) kinase signal cascade. Our results indicate that depression of PPARγ expression and activity is involved in HSC proliferation and that the PPARγ ligand-mediated activation exerts a previously unrecognized inhibition of PDGF-induced mitogenesis in activated human HSC.
Anthropometric Prediction of Total Body Water in Children Who Are on Pediatric Peritoneal Dialysis
Authors: Bruce Z. Morgenstern, Elke Wühl, K. Sreekumaran Nair, Bradley A. Warady, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2005)

Accurate estimation of total body water (TBW) is a critical component of dialysis prescription in peritoneal dialysis (PD). Gold-standard isotope dilution techniques are laborious and costly; therefore, anthropometric prediction equations that are based on height and weight are commonly used to estimate TBW. Equations have been established in healthy populations, but their validity is unclear in children who undergo PD, in whom altered states of hydration and other confounding alterations in normal physiology, particularly retarded growth and pubertal delay, may exist. TBW was measured by heavy water (H2O18 or D2O) dilution in 64 pediatric patients who were aged 1 mo to 23 yr and receiving chronic PD in the United States and Germany to establish and validate population-specific anthropometric TBW prediction equations and to compare the predictive power of these equations with formulas that have been established in healthy children. The best-fitting equations are as follows: For boys, TBW = 0.10 x (HtWt)0.68 - 0.37 x weight; for girls, TBW = 0.14 x (HtWt)0.64 - 0.35 x weight. The height x weight parameter also predicts body surface area (BSA). These equations can be simplified, with slightly less precision, to the following: For boys, TBW = 20.88 x BSA - 4.29; for girls, TBW = 16.92 x BSA - 1.81. TBW is predicted without systematic deviations and equally well in boys and girls, North American and European, obese and nonobese, growth-retarded and normally sized, and pre- and postpubertal children. In contrast, previous anthropometric equations that were derived from healthy children systematically overpredicted TBW and were less precise in this pediatric PD population. In summary, a new set of anthropometric TBW prediction equations that are suited specifically for use in pediatric PD patients have been provided.