tbuckley/cabot-search huggingface dataset:
The effects of creatine supplementation on selected factors of tennis specific training
Authors: B M Pluim, A Ferrauti, F Broekhof, M Deutekom, A Gotzmann, H Kuipers, K Weber
Journal: British Journal of Sports Medicine (2006)

Creatine supplementation is popular among tennis players but it is not clear whether it actually enhances tennis performance.To examine the effects of creatine supplementation on tennis specific performance indices.In a randomised, double blind design, 36 competitive male tennis players (24 creatine, mean (SD) age, 22.5 (4.9) years; 12 placebo, 22.8 (4.8) years) were tested at baseline, after six days of creatine loading, and after a maintenance phase of four weeks (14 creatine, 10 placebo). Serving velocity (10 serves), forehand and backhand velocity (three series of 5x8 strokes), arm and leg strength (bench press and leg press), and intermittent running speed (three series of five 20 metre sprints) were measured.Compared with placebo, neither six days nor five weeks of creatine supplementation had a significant effect on serving velocity (creatine: +2 km/h; placebo: +2 km/h, p = 0.90); forehand velocity (creatine: +4 km/h; placebo: +4 km/h, p = 0.80), or backhand velocity (creatine: +3 km/h; placebo: +1 km/h, p = 0.38). There was also no significant effect of creatine supplementation on repetitive sprint power after 5, 10, and 20 metres, (creatine 20 m: -0.03 m/s; placebo 20 m: +0.01 m/s, p = 0.18), or in the strength of the upper and lower extremities.Creatine supplementation is not effective in improving selected factors of tennis specific performance and should not be recommended to tennis players.
Characterization of Torin2, an ATP-Competitive Inhibitor of mTOR, ATM, and ATR
Authors: Qingsong Liu, Chunxiao Xu, Sivapriya Kirubakaran, Xin Zhang, Wooyoung Hur, Yan Liu, Nicholas P. Kwiatkowski, Jinhua Wang, Kenneth D. Westover, Peng Gao, Dalia Ercan, Mario Niepel, Carson C. Thoreen, Seong A. Kang, Matthew P. Patricelli, Yuchuan Wang, Tanya Tupper, Abigail Altabef, Hidemasa Kawamura, Kathryn D. Held, Danny M. Chou, Stephen J. Elledge, Pasi A. Janne, Kwok-Kin Wong, David M. Sabatini, Nathanael S. Gray
Journal: Cancer Research (2013)

Abstract mTOR is a highly conserved serine/threonine protein kinase that serves as a central regulator of cell growth, survival, and autophagy. Deregulation of the PI3K/Akt/mTOR signaling pathway occurs commonly in cancer and numerous inhibitors targeting the ATP-binding site of these kinases are currently undergoing clinical evaluation. Here, we report the characterization of Torin2, a second-generation ATP-competitive inhibitor that is potent and selective for mTOR with a superior pharmacokinetic profile to previous inhibitors. Torin2 inhibited mTORC1-dependent T389 phosphorylation on S6K (RPS6KB1) with an EC50 of 250 pmol/L with approximately 800-fold selectivity for cellular mTOR versus phosphoinositide 3-kinase (PI3K). Torin2 also exhibited potent biochemical and cellular activity against phosphatidylinositol-3 kinase–like kinase (PIKK) family kinases including ATM (EC50, 28 nmol/L), ATR (EC50, 35 nmol/L), and DNA-PK (EC50, 118 nmol/L; PRKDC), the inhibition of which sensitized cells to Irradiation. Similar to the earlier generation compound Torin1 and in contrast to other reported mTOR inhibitors, Torin2 inhibited mTOR kinase and mTORC1 signaling activities in a sustained manner suggestive of a slow dissociation from the kinase. Cancer cell treatment with Torin2 for 24 hours resulted in a prolonged block in negative feedback and consequent T308 phosphorylation on Akt. These effects were associated with strong growth inhibition in vitro. Single-agent treatment with Torin2 in vivo did not yield significant efficacy against KRAS-driven lung tumors, but the combination of Torin2 with mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibitor AZD6244 yielded a significant growth inhibition. Taken together, our findings establish Torin2 as a strong candidate for clinical evaluation in a broad number of oncologic settings where mTOR signaling has a pathogenic role. Cancer Res; 73(8); 2574–86. ©2013 AACR.
Noma: an “infectious” disease of unknown aetiology
Authors: Denise Baratti-Mayer, Brigitte Pittet, Denys Montandon, Ignacio Bolivar, Jacques-Etienne Bornand, Stéphane Hugonnet, Alexandre Jaquinet, Jacques Schrenzel, Didier Pittet
Journal: The Lancet Infectious Diseases (2003)
Seeking Proof Where the Subject is Ill-Defined and the Outcomes Limited
Authors: Karolyn Leslea White, Michael Carey, Ian Kerridge
Journal: The American Journal of Bioethics (2008)

The authors of this study concludes that ethics education has a positive influence on moral confidence, moral action and the use of ethics resources by nurses and social workers.A crucial limitation of the study is that it does not provide any way for respondents to indicate what they understand by ethics nor the ethical content of their educational programs, thus we cannot properly assess the basis of the respondents confidence about their professional and ethical responsibilities.This is reinforced by the possibility that respondents' ethical understandings have been shaped by experiences independent of formal education programs.Moreover, the findings that inservice ethical training is strongly correlated with moral confidence and action are problematic because what counts as ethics, rather than law or hospital policy for example, is not elucidated.
Detection of rheumatoid arthritis bone erosions by two different dedicated extremity MRI units and conventional radiography
Authors: A Duer-Jensen, A Vestergaard, U M Dohn, B Ejbjerg, M L Hetland, E Albrecht-Beste, M Ostergaard
Journal: Annals of the Rheumatic Diseases (2007)

To compare the ability of two different dedicated extremity MRI (E-MRI) units and conventional radiography (CR) for identifying bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) and wrist joints.CR and two MRI examinations (using 0.2 T Esaote Artoscan and 0.2 T portable MagneVu MV1000 units) of 418 bones in the dominant wrist and second to fifth MCP joints of 15 patients with RA and 4 healthy controls were performed and evaluated blindly for bones being visible and for erosions.In MCP joints, MagneVu visualised 18.5% of bones entirely and 71.1% were 67-99% visualised. In wrists, MagneVu visualised 1.5% of bones entirely, 39.8% were 67-99% visualised and 19% were not visualised at all. Artoscan and CR visualised all bones entirely. Artoscan, MagneVu and CR found 22, 19 and 15 bones with erosions in MCP joints and 66, 40 and 13 bones with erosions in wrist joints, respectively. With the previously validated Artoscan unit as standard reference, MagneVu and CR had sensitivities of 0.82 and 0.55, respectively, in MCP joint bones and 0.41 and 0.14 in wrist bones. Specificities of CR and MagneVu were comparable (0.82-0.99). The MagneVu unit was particularly more sensitive than CR for metacarpal heads and carpal bones. MagneVu MRI and CR detected 100% and 89%, respectively, of large erosions (Outcome Measures in Rheumatoid Arthritis Clinical Trials-Rheumatoid Arthritis MRI Scoring System (OMERACT-RAMRIS) score >1 on Artoscan) in MCP joints and 69% and 15.8% of large erosions in wrists.Both E-MRI units detected more erosions than CR, in particular due to a higher sensitivity in metacarpal heads and carpal bones. The MagneVu unit detected fewer erosions than the Artoscan unit due to a lower average image quality and a smaller proportion of bones being visualised.
CD19 is a major B cell receptor–independent activator of MYC-driven B-lymphomagenesis
Authors: Elaine Y. Chung, James N. Psathas, Duonan Yu, Yimei Li, Mitchell J. Weiss, Andrei Thomas-Tikhonenko
Journal: Journal of Clinical Investigation (2012)

PAX5, a B cell-specific transcription factor, is overexpressed through chromosomal translocations in a subset of B cell lymphomas. Previously, we had shown that activation of immunoreceptor tyrosine-based activation motif (ITAM) proteins and B cell receptor (BCR) signaling by PAX5 contributes to B-lymphomagenesis. However, the effect of PAX5 on other oncogenic transcription factor-controlled pathways is unknown. Using a MYC-induced murine lymphoma model as well as MYC-transformed human B cell lines, we found that PAX5 controls c-MYC protein stability and steady-state levels. This promoter-independent, posttranslational mechanism of c-MYC regulation was independent of ITAM/BCR activity. Instead it was controlled by another PAX5 target, CD19, through the PI3K-AKT-GSK3β axis. Consequently, MYC levels in B cells from CD19-deficient mice were sharply reduced. Conversely, reexpression of CD19 in murine lymphomas with spontaneous silencing of PAX5 boosted MYC levels, expression of its key target genes, cell proliferation in vitro, and overall tumor growth in vivo. In human B-lymphomas, CD19 mRNA levels were found to correlate with those of MYC-activated genes. They also negatively correlated with the overall survival of patients with lymphoma in the same way that MYC levels do. Thus, CD19 is a major BCR-independent regulator of MYC-driven neoplastic growth in B cell neoplasms.
Craniopharyngioma in Two Siblings
Authors: J. Rodolfo Vargas
Journal: JAMA (1981)

WE DESCRIBE two siblings, both with gradual development of symptoms of diabetes insipidus and panhypopituitarism, in whom craniopharyngiomas were found. <h3>Report of Cases</h3><h3>Case 1.—</h3> A boy who had been treated intermittently for diabetes insipidus for seven years and for panhypopituitarism for five years came under our care in 1974 at age 16 years. He was prepubertal, weighed 20.6 kg, was 140 cm tall, and had grown 3 cm in height during the preceding five years. Physical examination revealed bitemporal hemianopsia and bilateral nasal optic disc atrophy. The neurological examination findings were normal. Simultaneous urine and plasma osmolalities were 207 and 295 mOsm/kg, respectively. The EEG revealed occasional focal slowing in the bitemporal region. Endocrine studies indicated panhypopituitarism (Table). Radiological studies revealed generalized enlargement of the sella turcica with ballooned floor and erosion of the dorsum sellae. A pneumoencephalogram demonstrated an intrasellar mass with 7 mm of suprasellar extension. The
SEROLOGICAL RELATIONSHIP BETWEEN PNEUMOCOCCUS TYPE I AND AN ENCAPSULATED STRAIN OF ESCHERICHIA COLI
Authors: L. A. Barnes, Eleanor C. Wight
Journal: The Journal of Experimental Medicine (1935)

An encapsulated strain of Escherichia coli has been isolated which is hemolytic, pathogenic for mice, and which has served to illustrate further evidence of heterogenetic specificity. The relationship appears to be limited to the serological reactions between the colon organism and Type I antipneumococcic horse serum. Type I antipneumococcic rabbit serum failed to agglutinate the organism and no reactions occurred with Types II and III antipneumococcic horse serums, normal horse serum, and a variety of other immune horse serums. Serum from rabbits immunized with the colon bacillus agglutinated the homologous organism and precipitated its soluble substance, but failed to cause agglutination of Type I pneumococci or to precipitate Type I pneumococcic polysaccharide. The evidence indicates a connection somewhat analogous to that between Type II pneumococcus and Type B Friedländer's bacillus.
The Confirmatory Trial in Comparative-Effectiveness Research
Authors: Alan M. Garber, Mark A. Hlatky
Journal: New England Journal of Medicine (2009)

Despite the infusion of more than $1 billion through the American Recovery and Reinvestment Act of 2009 and the potential commitment of much more money, there will never be enough funding to perform all the comparative-effectiveness studies that we want. The depth of interest in such studies became apparent when the Committee on Comparative Effectiveness Research Prioritization of the Institute of Medicine received more than 1200 nominations of distinct topics to be among the first supported under the act.1 Thus, a critical question is how to choose the studies that will be supported with substantial, but not unlimited, funds. How . . .
Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials
Authors: C Salliot, M Dougados, L Gossec
Journal: Annals of the Rheumatic Diseases (2008)

Background: Tumour necrosis factor α blockers in rheumatoid arthritis are known to increase the risk of serious infections defined as life-threatening, requiring hospitalisation or intravenous antibiotics. Recently, new biological agents have become available. Their safety is an important issue. Purpose: To assess if biological agents, ie rituximab, abatacept and anakinra increase the risk of serious infections in patients with rheumatoid arthritis in published randomised controlled trials. Data source: A systematic review of the literature using PUBMED, EMBASE, Cochrane library and abstracts databases (American College of Rheumatology and European League Against Rheumatism annual meetings) was performed up to October 2007. This search was completed with data from the Food and Drug Administration, the European Agency for the Evaluation of Medicinal Products and manufacturers. Data extraction: Three fixed-effect meta-analyses were performed to compare serious infection rates between each biological agent and placebo. Pooled odds ratios (ORs) were calculated, using the Mantel–Haenszel method with a continuity correction. Data synthesis: Twelve randomised controlled trials with data concerning serious infections were analysed (three for rituximab, five for abatacept and four for anakinra). They included 745 patients, 1960 patients, 2062 patients and 2112 patients treated by rituximab, abatacept, anakinra and placebo respectively. The overall pooled ORs did not reveal a statistically significant increased risk of serious infection for abatacept and rituximab; this risk was increased for high doses of anakinra (⩾100 mg daily) versus low dose and placebo (ORs = 9.63 (95% CI, 1.31 to 70.91) and 3.40 (95% CI, 1.11 to 10.46) respectively). Conclusions: These meta-analyses did not reveal a significant increase in the risk of serious infections during rituximab or abatacept treatments in patients with rheumatoid arthritis; however, high doses of anakinra may increase this risk, especially when patients have comorbidity factors. Large studies must be performed to confirm this safety profile in daily practice.
Smoking is associated with the incidence of AMS: a large-sample cohort study
Authors: Pan Song, Ji-hang Zhang, Jun Qin, Xu-bin Gao, Jie Yu, Xu-gang Tang, Cai-fa Tang, Lan Huang
Journal: Military Medical Research (2014)

In recent years, the number of people visiting high altitudes has increased. After rapidly ascending to a high altitude, some of these individuals, who reside on plains or other areas of low altitude, have suffered from acute mountain sickness (AMS). Smoking interferes with the body's oxygen metabolism, but research about the relationship between smoking and AMS has yielded controversial results. We collected demographic data, conducted a smoking history and performed physical examinations on 2000 potential study participants, at sea level. Blood pressure (BP) and pulse oxygen saturation (SpO2) were measured for only some of the patients due to time and manpower limitations. We ultimately recruited 520 smokers and 450 nonsmokers according to the inclusion and exclusion criteria of our study. Following acute high-altitude exposure, we examined their Lake Louise Symptom (LLS) scores, BP, HR and SpO2; however, cerebral blood flow (CBF) was measured for only some of the subjects due to limited time, manpower and equipment. Both the incidence of AMS and Lake Louise Symptom (LLS) scores were lower in smokers than in nonsmokers. Comparing AMS-related symptoms between nonsmokers and smokers, the incidence and severity of headaches and the incidence of sleep difficulties were lower in smokers than in nonsmokers. The incidences of both cough and mental status change were higher in smokers than in nonsmokers; blood pressure, HR and cerebral blood flow velocity were lower in smokers than in nonsmokers. Our findings suggest that the incidence of AMS is lower in the smoking group, possibly related to a retardation of cerebral blood flow and a relief of AMS-related symptoms, such as headache.
Telomere Loss as a Mechanism for Chromosome Instability in Human Cancer
Authors: John P. Murnane
Journal: Cancer Research (2010)

Cancer cells commonly have a high rate of telomere loss, even when expressing telomerase, contributing to chromosome instability and tumor cell progression. This review addresses the hypothesis that this high rate of telomere loss results from a combination of four factors. The first factor is an increase in the frequency of double-strand breaks (DSB) at fragile sites in cancer cells due to replication stress. The second factor is that telomeres are fragile sites. The third factor is that subtelomeric regions are highly sensitive to DSBs, so that DSBs near telomeres have an increased probability of resulting in chromosome instability. The fourth factor is that cancer cells may be deficient in chromosome healing, the de novo addition of telomeres to the sites of DSBs, a mechanism that prevents chromosome instability resulting from DSBs near telomeres. Understanding these factors and how they influence telomere loss will provide important insights into the mechanisms of chromosome instability and the development of novel approaches for anti-cancer therapy. Cancer Res; 70(11); 4255-9. (c)2010 AACR.
Apolipoprotein E genotypes and risk of diabetic nephropathy.
Authors: T Onuma, L M Laffel, M C Angelico, A S Krolewski
Journal: Journal of the American Society of Nephrology (1996)

Genetic susceptibility contributes to the development of diabetic nephropathy. In considering potentially important genetic factors, this study examined the association between genetic polymorphisms in apolipoprotein (apo) E and diabetic nephropathy in 146 patients with insulin-dependent diabetes mellitus (IDDM) of 15 to 21 years' duration. Using a case-control study design, patients with proteinuria (N = 41) (albumin excretion rate (AER) > or = 250 micrograms/min) and patients with microalbuminuria (N = 31) (AER 20 to 250 micrograms/min) were compared with patients who had normoalbuminuria (N = 74) (AER < 20 micrograms/min). Genetic polymorphisms at the apo E locus were identified by the method of denaturing gradient-gel electrophoresis. There was no significant difference in allele frequencies in the proteinuric, microalbuminuric, or normoalbuminuric groups (e2 7.3%, 9.7%, 9.5%; e3 78.1%, 72.6%, 68.2%; e4 14.6%, 17.7%, 22.3%; respectively). The distribution of the apo E genotypes among the three groups of patients was also similar. These results suggest that apo E genotypes are not associated with the development of early or advanced diabetic nephropathy in patients with IDDM.
A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor–deficient mice
Authors: Natalie A. Sims, Philippe Clément-Lacroix, Dominique Minet, Caroline Fraslon-Vanhulle, Martine Gaillard-Kelly, Michèle Resche-Rigon, Roland Baron
Journal: Journal of Clinical Investigation (2003)

Although the role of estradiol in maintaining bone mass is well established, the relative contributions of the estradiol receptors ERα and ERβ and of the androgen receptor (AR) remain controversial. To determine the role of ERα-mediated, ERβ-mediated, and non–ER-mediated mechanisms in maintaining bone mass, gonadectomy and estradiol treatment were studied in ER-knockout mice. Estradiol treatment of ovariectomized ERαβ–/– mice failed to prevent bone loss, precluding significant effects of estradiol on bone through non–ER-signaling pathways. In contrast, estradiol prevented ovariectomy-induced bone loss in ERβ–/– mice, as in WT males and females, indicating that ERα is the major mediator of estradiol effects in bone. No response of bone to estradiol was detected in orchidectomized ERα–/– mice, suggesting estradiol cannot protect bone mass via the AR in vivo. In contrast to female ERαβ–/– and male ERα–/– mice, female ERα–/– mice were partially protected against ovariectomy-induced bone loss by estradiol, confirming that ERβ mediates estradiol effects in bone, but only in females and with a lower efficacy than ERα. We conclude that ERα is the main effector of estradiol’s protective function in bone in both male and female mice, and that, in its absence, AR is not sufficient to mediate this response.
Cytoreductive Surgery Combined With Perioperative Intraperitoneal Chemotherapy for the Management of Peritoneal Carcinomatosis From Colorectal Cancer: A Multi-Institutional Study
Authors: O. Glehen, F. Kwiatkowski, P.H. Sugarbaker, D. Elias, E.A. Levine, M. De Simone, R. Barone, Y. Yonemura, F. Cavaliere, F. Quenet, M. Gutman, A.A.K. Tentes, G. Lorimier, J.L. Bernard, J.M. Bereder, J. Porcheron, A. Gomez-Portilla, P. Shen, M. Deraco, P. Rat
Journal: Journal of Clinical Oncology (2004)

The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival.A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded.The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators.The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.