tbuckley/cabot-search huggingface dataset:
Autograft Reinforcement to Preserve Autograft Function After the Ross Procedure
Authors: Efstratios I. Charitos, Thorsten Hanke, Ulrich Stierle, Derek R. Robinson, Ad J.J.C. Bogers, Wolfgang Hemmer, Matthias Bechtel, Martin Misfeld, Armin Gorski, Juergen O. Boehm, Joachim G. Rein, Cornelius A. Botha, Ruediger Lange, Juergen Hoerer, Anton Moritz, Thorsten Wahlers, Ulrich F.W. Franke, Martin Breuer, Katharina Ferrari-Kuehne, Roland Hetzer, Michael Huebler, Gerhard Ziemer, Johanna J.M. Takkenberg, Hans H. Sievers
Journal: Circulation (2009)

Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis.1335 adult patients (mean age:43.5+/-12.0 years) underwent a Ross procedure (subcoronary, SC, n=637; root replacement, Root, n=698). 592 patients received R of the annulus, sinotubular junction, or both. Regular clinical and echocardiographic follow-up was performed (mean:6.09+/-3.97, range:0.01 to 19.2 years). Longitudinal assessment of autograft function with time was performed using multilevel modeling techniques. The Root without R (Root-R) group was associated with a 6x increased reoperation rate compared to Root with R (Root+R), SC with R (SC+R), and without R (SC-R; 12.9% versus 2.3% versus 2.5%.versus 2.6%, respectively; P<0.001). SC and Root groups had similar rate of aortic regurgitation (AR) development over time. Root+R patients had no progression of AR, whereas Root-R had 6 times higher AR development compared to Root+R. In SC, R had no remarkable effect on the annual AR progression. The SC technique was associated with lower rates of autograft dilatation at all levels of the aortic root compared to the Root techniques. R did not influence autograft dilatation rates in the Root group.For the time period of the study surgical autograft stabilization techniques preserve autograft function and result in significantly lower reoperation rates. The nonreinforced Root was associated with significant adverse outcome. Therefore, surgical stabilization of the autograft is advisable to preserve long-term autograft function, especially in the Root Ross procedure.
Sex Steroids and the Construction and Conservation of the Adult Skeleton
Authors: B. Lawrence Riggs, Sundeep Khosla, L. Joseph Melton
Journal: Endocrine Reviews (2002)

Abstract Here we review and extend a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) as the key hormone for maintaining bone mass and E deficiency as the major cause of age-related bone loss in both sexes. Also, both E and testosterone (T) are key regulators of skeletal growth and maturation, and E, together with GH and IGF-I, initiate a 3- to 4-yr pubertal growth spurt that doubles skeletal mass. Although E is required for the attainment of maximal peak bone mass in both sexes, the additional action of T on stimulating periosteal apposition accounts for the larger size and thicker cortices of the adult male skeleton. Aging women undergo two phases of bone loss, whereas aging men undergo only one. In women, the menopause initiates an accelerated phase of predominantly cancellous bone loss that declines rapidly over 4–8 yr to become asymptotic with a subsequent slow phase that continues indefinitely. The accelerated phase results from the loss of the direct restraining effects of E on bone turnover, an action mediated by E receptors in both osteoblasts and osteoclasts. In the ensuing slow phase, the rate of cancellous bone loss is reduced, but the rate of cortical bone loss is unchanged or increased. This phase is mediated largely by secondary hyperparathyroidism that results from the loss of E actions on extraskeletal calcium metabolism. The resultant external calcium losses increase the level of dietary calcium intake that is required to maintain bone balance. Impaired osteoblast function due to E deficiency, aging, or both also contributes to the slow phase of bone loss. Although both serum bioavailable (Bio) E and Bio T decline in aging men, Bio E is the major predictor of their bone loss. Thus, both sex steroids are important for developing peak bone mass, but E deficiency is the major determinant of age-related bone loss in both sexes.
Effects of the introduction of new vaccines in Guinea-Bissau on vaccine coverage, vaccine timeliness, and child survival: an observational study
Authors: Ane B Fisker, Linda Hornshøj, Amabelia Rodrigues, Ibraima Balde, Manuel Fernandes, Christine S Benn, Peter Aaby
Journal: The Lancet Global Health (2014)

In 2008, the GAVI Alliance funded the introduction of new vaccines (including pentavalent diphtheria-tetanus-pertussis [DTP] plus hepatitis B and Haemophilus influenzae type b antigens) in Guinea-Bissau. The introduction was accompanied by increased vaccination outreach services and a more restrictive wastage policy, including only vaccinating children younger than 12 months. We assessed coverage of all vaccines in the Expanded Program on Immunizations before and after the new vaccines' introduction, and the implications on child survival.This observational cohort study used data from the Bandim Health Project, which has monitored vaccination status and mortality in randomly selected village clusters in Guinea-Bissau since 1990. We assessed the change in vaccination coverage using cohort data from children born in 2007 and 2009; analysed the proportion of children who received measles vaccine after 12 months of age using data from 1999-2006; and compared child mortality after age 12 months in children who had received measles vaccine and those who had not using data from 1999 to 2006.The proportion of children who were fully vaccinated by 12 months of age was 53% (468 of 878) in the 2007 cohort and 53% (467 of 879) in the 2009 cohort (relative risk [RR] 1·00, 95% CI 0·89-1·11). Coverage of DTP-3 and pentavalent-3 increased from 73% (644 of 878) in 2007 to 81% (712 of 879) in 2009 (RR 1·10, 95% CI 1·04 -1·17); by contrast, the coverage of measles vaccination declined from 71% (620 of 878) to 66% (577 of 879; RR 0·93, 0·85-1·01). The effect of the changes was significantly different for DTP-3 coverage compared with measles vaccine coverage (p=0·002). After 12 months of age, the adjusted mortality rate ratio was 0·71 (95% CI 0·56-0·90) for children who had received measles vaccine compared with those who had not (0·59 [0·43-0·80] for girls and 0·87 [0·62-1·23] for boys).The introduction of the new vaccination programme in 2008 was associated with increased coverage of DTP, but decreased coverage of measles vaccine. In 1999-2006, child mortality was higher in children who had not received measles vaccine than in those who had.DANIDA, European Research Council, the Danish Independent Research Council, European Union FP7 via OPTIMUNISE, and Danish National Research Foundation.
Isolation and partial characterization of the human homologue of Thy-1.
Authors: E W Ades, R K Zwerner, R T Acton, C M Balch
Journal: The Journal of Experimental Medicine (1980)

A glycoprotein of 25,000 daltons was isolated from a human T lymphoblastoid cell line (MOLT-3). A monovalent antiserum raised against this antigen precipitated mouse Thy-1.1 antigen as well as a 25,000-dalton antigen from human blood T cells. The unabsorbed serum was also cytotoxic for both mouse and human T cells. By multiple criteria, this human T antigen appears to be homologous with mouse Thy-1.
Abdominal Aortic Aneurysm with Rupture into the Inferior Vena Cava
Authors: WILLIAM N. VIAR, THOMAS A. LOMBARDO
Journal: Circulation (1952)

A patient is presented with an arteriosclerotic abdominal aneurysm that ruptured into the inferior vena cava. Clinically, the picture was that of a peripheral arteriovenous communication with heart failure of the "high-output" type. Intestinal bleeding occurred as a result of venous engorgement and hemorrhagic colitis.
Bedside to bench: a look at experimental research with a clinical trial checklist
Authors: K. R. Sipido, B. Casadei, P. Holvoet, S. Janssens, A. Luttun, M. Sampaolesi
Journal: Cardiovascular Research (2013)

Editors across all disciplines and approaches ask the same questions to reviewers and judge the merit of a study against a similar checklist: is the study well designed and does it provide reliable findings? Have we learnt something new? Are the results relevant to the community of scientists and/or medical professionals? In short, does the study make an important contribution to existing knowledge?

As clinical practice has become increasingly evidence-based, the number of clinical trials has increased significantly (Presently, >6500 trials with ‘heart’ as keyword are registered and are open or recruiting; www.clinicaltrials.gov.) and stringent criteria have been put into place to guide the design, execution, and analysis of clinical investigations.These are the standards of good clinical practice (“GCP is an international ethical and scientific quality standard for designing, recording, and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety, and wellbeing of trial subjects are protected, and that clinical-trial data are credible”; http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general\_content\_000072.jsp). Training courses are available to educate clinicians in GCP and the management of patient-based studies. In the past 10 years, the impact factor of journals that focus on clinical research has steadily increased, due, to a large extent, to the recognition that large, well-designed clinical trials are able to produce robust findings that are immediately relevant to patient management and underpin practice guidelines. (The AHA and ACC published more than 70 guidelines in their journals since 2005; http://my.americanheart.org/professional/StatementsGuidelines, and the ESC similarly published more than 30; http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/GuidelinesList.aspx.) Not surprisingly, this results in widespread citation of the work, reflecting its impact on the community.1,2

The care in the design, conduct, and analysis of a clinical trial, and the subsequent further scrutiny in meta-analysis, outcome research, and registries are motivated by …
Janus Kinase 3–Activating Mutations Identified in Natural Killer/T-cell Lymphoma
Authors: Ghee Chong Koo, Soo Yong Tan, Tiffany Tang, Song Ling Poon, George E. Allen, Leonard Tan, Soo Ching Chong, Whee Sze Ong, Kevin Tay, Miriam Tao, Richard Quek, Susan Loong, Kheng-Wei Yeoh, Swee Peng Yap, Kuo Ann Lee, Lay Cheng Lim, Daryl Tan, Christopher Goh, Ioana Cutcutache, Willie Yu, Cedric Chuan Young Ng, Vikneswari Rajasegaran, Hong Lee Heng, Anna Gan, Choon Kiat Ong, Steve Rozen, Patrick Tan, Bin Tean Teh, Soon Thye Lim
Journal: Cancer Discovery (2012)

The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs.Gene mutations causing NKTCL have not been fully identified. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Our findings have important implications for the management of patients with NKTCLs.
<i>Coxiella burnetii</i>pneumonia
Authors: T.J. Marrie
Journal: European Respiratory Journal (2003)

This report reviews the pulmonary and extrapulmonary manifestation of infections due to Coxiella burnetii . Q fever, a zoonosis, is due to infection with C. burnetii . This spore-forming microorganism is a small Gram-negative coccobacillus that is an obligate intracellular parasite. The most common animal reservoirs are goats, cattle, sheep, cats, and occasionally dogs. The organism reaches high concentrations in the placenta of infected animals. Aerosolisation occurs at the time of parturition and infection follows inhalation of this aerosol. There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis. The chronic form of Q fever is almost always endocarditis, but occasionally it is manifest as hepatitis, osteomyelitis or endovascular infection. The pneumonic form of the illness can range from very mild-to-severe pneumonia requiring assisted ventilation. Multiple round opacities are a common finding on chest radiography. Treatment with doxycycline or a fluoroquinolone is preferred. Susceptibility to macrolides is variable. In conclusion, Coxiella burnetii pneumonia should be considered when there is a suitable exposure history and when outbreaks of a pneumonic illness are being investigated.
Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice.
Authors: E Montaña, S Bonner-Weir, G C Weir
Journal: Journal of Clinical Investigation (1993)

In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication.
Psoriasis: an evidence-based update. Report of the 9th Evidenced Based Update Meeting, 12 May 2011, Loughborough, U.K.
Authors: P. De Mozzi, G.A. Johnston, A.B. Alexandroff
Journal: British Journal of Dermatology (2012)

The Centre of Evidence Based Dermatology, University of Nottingham, U.K. holds an annual Evidence Based Update (EBU) Meeting focused on important dermatological topics, which have in the past included eczema, urticaria, blistering disorders, skin infections, skin cancer and hair disorders. These one-day meetings aim to summarize the most recent evidence in the form of systematic reviews and recently completed clinical trials. This year, the 9th EBU meeting took place in Loughborough, U.K. on 12 May 2011 and was devoted to psoriasis. The latest updates on topical treatments, nail psoriasis, genetics and clinical implications, rational use of biologics, new and unpublished studies on combination of phototherapy and biologics for psoriasis, and on treatments of palmoplantar pustular psoriasis were discussed by a panel of renowned international speakers.
Development of a Scottish physical activity questionnaire: a tool for use in physical activity interventions.
Authors: M Lowther, N Mutrie, C Loughlan, C McFarlane
Journal: British Journal of Sports Medicine (1999)

Three studies were undertaken to establish the reliability and validity of the Scottish physical activity questionnaire (SPAQ), developed to aid seven day recall of leisure and occupational physical activity.To establish reliability, SPAQs (n = 34) were completed on a Monday and the following Wednesday. Thus each questionnaire measured four identical days. To establish concurrent validity, 94 participants completed a SPAQ and an adapted stage of exercise behaviour change questionnaire. Responses to SPAQ were then analysed by stage of exercise behaviour change. In a further study of criterion validity, 30 volunteers wore a Caltrac motion sensor for four consecutive days, after which they completed a SPAQ.In the first study, total physical activity had a coefficient of repeatability (R) of 53 minutes. Occupational physical activity showed a similar variance (R = 54.6 minutes) but leisure physical activity was more reliable (R = 29.3 minutes). The main variation in occupational physical activity was found to be walking (R = 39.8 minutes). In study 2, a one way analysis of variance showed the expected relation between physical activity and stage of exercise behaviour change, confirming the concurrent validity of SPAQ with the stage of exercise behaviour change model. In study 3, several erroneous recordings affected both SPAQ and the Caltrac results (kcal). After relevant corrections had been made, the correlation between the two measurement devices was 0.52 (p < 0.05).SPAQ has been shown to be reliable and to hold strong concurrent validity and limited criterion validity. The main limitation in SPAQ appears to be the measurement of occupational walking. It is therefore recommended that further work be conducted to refine the measurement of this physical activity component. It is evident nonetheless that SPAQ can be used with confidence to measure outcomes in physical activity interventions when account is taken of its limitations.
RNAi: a novel strategy for the treatment of prion diseases
Authors: Qingzhong Kong
Journal: Journal of Clinical Investigation (2006)

Prion disease refers to a group of fatal transmissible neurodegenerative diseases for which no pharmacological treatment is available. The cellular prion protein (PrP(C)) is required for both prion replication and pathogenesis, and reducing PrP(C) levels has been shown to extend survival time after prion infection. RNA interference (RNAi) is a sequence-specific posttranscriptional gene silencing mechanism. In this issue of the JCI, Pfeifer et al. report that lentivector-mediated RNAi significantly reduced neuronal PrP(C) expression; effectively suppressed accumulation of the infectious protease-resistant form of PrP (PrP(Sc)) in a persistently infected neuroblastoma cell line; and markedly slowed the progression of prion disease in a unique chimeric mouse model (see the related article beginning on page 3204). These findings indicate that lentivector-mediated RNAi could, in principle, be developed for the therapy of prion disease.
Myogenic Endothelial Cells Purified From Human Skeletal Muscle Improve Cardiac Function After Transplantation Into Infarcted Myocardium
Authors: Masaho Okada, Thomas R. Payne, Bo Zheng, Hideki Oshima, Nobuo Momoi, Kimimasa Tobita, Bradley B. Keller, Julie A. Phillippi, Bruno Péault, Johnny Huard
Journal: Journal of the American College of Cardiology (2008)
Screening older cancer patients: first evaluation of the G-8 geriatric screening tool
Authors: C.A. Bellera, M. Rainfray, S. Mathoulin-Pélissier, C. Mertens, F. Delva, M. Fonck, P.L. Soubeyran
Journal: Annals of Oncology (2012)

Development of a geriatric screening tool is necessary to identify elderly cancer patients who would benefit from comprehensive geriatric assessment (CGA). We develop and evaluate the G-8 screening tool against various reference tests.
Genome-wide mapping of human loci for essential hypertension
Authors: Mark Caulfield, Patricia Munroe, Janine Pembroke, Nilesh Samani, Anna Dominiczak, Morris Brown, John Webster, Peter Ratcliffe, Suzanne O'Shea, Jeanette Papp, Elizabeth Taylor, Richard Dobson, Joanne Knight, Stephen Newhouse, Joel Hooper, Wai Lee, Nick Brain, David Clayton, G Mark Lathrop, Martin Farrall, John Connell, Nigel Benjamin
Journal: The Lancet (2003)
Sex Differences in the Phosphorylation of Mitochondrial Proteins Result in Reduced Production of Reactive Oxygen Species and Cardioprotection in Females
Authors: Claudia J. Lagranha, Anne Deschamps, Angel Aponte, Charles Steenbergen, Elizabeth Murphy
Journal: Circulation Research (2010)

Although premenopausal females have a lower risk for cardiovascular disease, the mechanism(s) are poorly understood.We tested the hypothesis that cardioprotection in females is mediated by altered mitochondrial protein levels and/or posttranslational modifications.Using both an in vivo and an isolated heart model of ischemia and reperfusion (I/R), we found that females had less injury than males. Using proteomic methods we found that female hearts had increased phosphorylation and activity of aldehyde dehydrogenase (ALDH)2, an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts, and that an activator of ALDH2 reduced I/R injury in males but had no significant effect in females. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, blocked the protection and the increased phosphorylation of ALDH2 in females, but had no effect in males. Furthermore, we found an increase in phosphorylation of alpha-ketoglutarate dehydrogenase (alphaKGDH) in female hearts. alphaKGDH is a major source of ROS generation particularly with a high NADH/NAD ratio which occurs during I/R. We found decreased ROS generation in permeabilized female mitochondria given alphaKGDH substrates and NADH, suggesting that increased phosphorylation of alphaKGDH might reduce ROS generation by alphaKGDH. In support of this hypothesis, we found that protein kinase C-dependent phosphorylation of purified alphaKGDH reduced ROS generation. Additionally, myocytes from female hearts had less ROS generation following I/R than males and addition of wortmannin increased ROS generation in females to the same levels as in males.These data suggest that posttranslational modifications can modify ROS handling and play an important role in female cardioprotection.