tbuckley/cabot-search huggingface dataset:
High-Producer Haplotypes of Tumor Necrosis Factor Alpha and Lymphotoxin Alpha Are Associated With an Increased Risk of Myeloma and Have an Improved Progression-Free Survival After Treatment
Authors: Faith E. Davies, Sara J. Rollinson, Andrew C. Rawstron, Eve Roman, Stephen Richards, Mark Drayson, J. Anthony Child, Gareth J. Morgan
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the effect of polymorphic variations in the tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTα) genes on the predisposition to myeloma and the effect of these polymorphisms on response to treatment and overall survival. PATIENTS AND METHODS: Genotype distribution was determined in 63 patients with monoclonal gammopathy of uncertain significance (MGUS) and 198 patients with myeloma and compared with that in 250 age- and sex-matched population-based controls. The effect on treatment response and survival was determined in 171 myeloma patients treated with either conventional or high-dose chemotherapy. RESULTS: Comparison of the extended TNFα/LTα haplotype in the myeloma cases and controls showed a significant excess of high-producer alleles in the cases. The double heterozygotes TNF1/2 and LT10.5/5.5 were present in 35.8% of cases but in only 18% of the controls; this presence was associated with a significant increased risk of myeloma (odds ratio, 2.05; 95% confidence interval, 1.26 to 3.35). A similar odds ratio was seen in the MGUS cases, suggesting that this genotype is associated with the initiation of plasma-cell disorders rather than the progression of MGUS to myeloma. The median overall survival time of myeloma patients was 53.8 months and showed no difference with regard to TNFα/LTα polymorphic status. A trend toward an improved progression-free survival was apparent in cases with a high-producer haplotype, although this effect was seen only in patients receiving high-dose chemotherapy. CONCLUSION: Individuals with polymorphisms associated with a high production of TNFα/LTα are at a significantly increased risk of developing MGUS and myeloma. The impact of polymorphic status on overall survival is minimal, although there is a trend toward an increased progression-free survival in the high-producer group.
Cardioprotection and Second Malignant Neoplasms Associated With Dexrazoxane in Children Receiving Anthracycline Chemotherapy: A Systematic Review and Meta-Analysis
Authors: Furqan Shaikh, L. Lee Dupuis, Sarah Alexander, Abha Gupta, Luc Mertens, Paul C. Nathan
Journal: JNCI Journal of the National Cancer Institute (2015)

Several randomized controlled trials (RCTs) have demonstrated that dexrazoxane reduces anthracycline cardiotoxicity in adults, but use in children has been hindered by lack of direct evidence of cardioprotection and concerns regarding second malignant neoplasms (SMNs). This study aimed to systematically review the evidence regarding dexrazoxane in children. We searched Medline, Embase, the Cochrane Library, and abstracts for RCTs and nonrandomized studies (NRSs) that compared dexrazoxane to no cardioprotection among children. We combined findings using random-effects models. All statistical tests were two-sided. Eleven eligible publications reported results from five RCTs (1254 patients), and 15 publications reported results from 12 NRSs (3385 patients). Dexrazoxane did not impact clinical cardiotoxicity in RCTs because of a low cardiotoxic event rate (three events among all patients) but was associated with a reduction in subclinical cardiotoxicity. Among NRSs, dexrazoxane was associated with a reduction in clinical cardiotoxicity (relative risk (RR) = 0.29, P = .001) and clinical+subclinical cardiotoxicity (RR = 0.43, P < .001). Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of acute myeloid leukemia, while one that used cranial radiation reported an increased risk of brain tumors. Event-free survival did not differ ( P = .91). Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol.
Alarming weight cutting behaviours in mixed martial arts: a cause for concern and a call for action
Authors: Ben Crighton, Graeme L Close, James P Morton
Journal: British Journal of Sports Medicine (2015)

Some nutritional practices in mixed martial arts (MMA) are dangerous to health, may contribute to death, and are largely unsupervised. MMA is a full contact combat sport (often referred to as cage fighting) that emerged to western audiences in 1993 via the Ultimate Fighting Championship (UFC). MMA is one of the world's fastest growing sports and now broadcasts to over 129 countries and 800 million households worldwide.

Underpinning the focus on weight controlling practices, lies MMA's competition structure of 11 weight classes (atomweight, 47.6 kg; strawweight 52.2 kg; flyweight, 56.7 kg; bantamweight, 61.2 kg; featherweight, 65.8 kg; lightweight, 70.3 kg; welterweight, 77.1 kg; middleweight, 83.9 kg; light-heavyweight, 93 kg; heavyweight, 120.2 kg; super-heavyweight, no limit) that are intended to promote fair competition by matching opponents of equal body mass. Athletes aim to compete at the lowest possible weight, usually achieved by rapid weight loss methods reliant on acute/chronic dehydration (eg, saunas, sweat suits, diuretics, hot baths, etc). Weigh-in occurs on the day before (24–36 h prior) competition therefore …
In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy
Authors: Grazia Serino, Francesco Pesce, Fabio Sallustio, Giuseppe De Palma, Sharon N. Cox, Claudia Curci, Gianluigi Zaza, Kar N. Lai, Joseph C.K. Leung, Sydney C.W. Tang, Aikaterini Papagianni, Maria Stangou, Dimitrios Goumenos, Miltiadis Gerolymos, Kazuo Takahashi, Yukio Yuzawa, Shoichi Maruyama, Enyu Imai, Francesco P. Schena
Journal: Kidney International (2015)
Biomaterials: Design of Hydrogels for Biomedical Applications (Adv. Healthcare Mater. 16/2015)
Authors: Hiroyuki Kamata, Xiang Li, Ung-il Chung, Takamasa Sakai
Journal: Advanced Healthcare Materials (2015)

Biomedical applications of hydrogels are often hindered by the difficulty in controlling their temporal change in shape in vivo. This morphological change may cause not only the slippage from the installation site but also local nerve compression. On page 2360, T. Sakai and co-workers show that the design of hydrogels that can retain their original shape and mechanical properties under physiological conditions is of great importance.
Vincristine and prednisone prolong the survival of patients receiving intravenous or oral melphalan for multiple myeloma: Cancer and Leukemia Group B experience.
Authors: G G Cornwell, T F Pajak, S Kochwa, O R McIntyre, L P Glowienka, K Brunner, S Rafla, M Coleman, M R Cooper, E Henderson
Journal: Journal of Clinical Oncology (1988)

A total of 589 patients with previously untreated multiple myeloma were randomized to receive daily oral melphalan, pulse-dose intravenous (IV) melphalan, carmustine (BCNU), or lomustine (CCNU). All patients received an initial tapering course of prednisone (Pred). During week 22 (day 154), patients were randomized to receive or not to receive additional therapy with vincristine (VCR) (1 mg/m2) and prednisone (0.6 mg/kg/d for seven days) at 8-week intervals. The influence of VCR/Pred was determined in 302 patients who remained on study beyond 22 weeks after initial therapy. VCR/Pred converted a significant percentage of nonresponders to responders in patients treated with melphalan (55% v 19%, P = .002), but not in patients treated with a nitrosourea (48% v 23%, P = .06). Survival beyond week 22 was significantly longer following the addition of VCR/Pred in patients receiving melphalan (median, 35.3 months v 27.0 months; P = .003) but not in patients receiving BCNU or CCNU (median, 28.1 months v 26.2 months; P = .91). These differences were seen both for oral and IV melphalan. A trend for beneficial effect of VCR/Pred was definitely seen in the good-risk patients (P = .03) but only suggestive for poor-risk patients (P = .12). Following adjustment for VCR/Pred effects, there were no differences in the survival of patients receiving any of the four initial treatments.
Consensus statement on the methodology of injury and illness surveillance in FINA (aquatic sports)
Authors: M Mountjoy, A Junge, J M Alonso, B Clarsen, B M Pluim, I Shrier, C van den Hoogenband, S Marks, D Gerrard, P Heyns, K Kaneoka, H P Dijkstra, K M Khan
Journal: British Journal of Sports Medicine (2015)

Background Injury and illness surveillance in the aquatic disciplines has been conducted during the FINA World Championships and Olympic Games. The development of an aquatic-specific injury and illness surveillance system will improve the quality of the data collected and the development of preventive measures. Our ultimate objective is to enhance aquatic athlete health and performance. Objective The objective was to refine the injury and illness surveillance protocols to develop aquatic-specific definitions of injury and illness; define aquatic-specific injury location and causation; better describe overuse injuries; regard pre-existing and recurrent injuries; more accurately define aquatic athlete exposures and develop a protocol to capture out-of-competition aquatic athlete health parameters. Methods FINA compiled an Injury and Illness Surveillance Expert Working Group comprised of international experts to review the scientific literature in the field. A consensus meeting was convened to provide an opportunity for debate, following which recommendations were collated. Results Aquatic-specific injury and illness surveillance protocols covering both the in-competition and out-of-competition time periods were developed. Definitions for all relevant variables were outlined, and documentation forms for athletes and for clinicians were proposed. Recommendations for the implementation of an injury and illness surveillance system for FINA are presented. Conclusion The FINA consensus authors recommend ongoing in-competition and out-of-competition surveillance to determine injury and illness trends over time. The implementation of the definitions and methodology outlined in this paper will improve the accuracy and value of injury and illness surveillance, and provide important information for injury prevention.
Nosocomial transmission of avian influenza virus A (H7N9)
Authors: M. A. B. van der Sande, W. van der Hoek
Journal: BMJ (2015)

We should not accept nosocomial transmission, of any pathogen, in any setting

Since the first notification in March 2013 through to 15 October 2015, a total of 679 laboratory confirmed cases of human infection with avian influenza A (H7N9) viruses, including 275 (40%) deaths, have been reported to the World Health Organization.1 These individuals have presumably contracted their infection in China directly from infected birds or their environment, particularly when visiting live poultry markets. Limited human to human transmission has been suspected in a few clusters of cases of family members.2 In a linked article, Fang and colleagues report on a presumed case of nosocomial, human to human, transmission of influenza A (H7N9) between unrelated individuals.3 Both patients, showing symptoms, spent time in the same hospital room, were infected with comparable strains, and—because no other common exposure was identified—the authors concluded that nosocomial infection was the most likely route of transmission.

Although Fang and colleagues’ report does not prove nosocomial transmission beyond any doubt, …
Palliative care for patients with advanced fibrotic lung disease: a randomised controlled phase II and feasibility trial of a community case conference intervention
Authors: Sabrina Bajwah, Joy R Ross, Athol U Wells, Kabir Mohammed, Christina Oyebode, Surinder S Birring, Amit S Patel, Jonathan Koffman, Irene J Higginson, Julia Riley
Journal: Thorax (2015)

<h3>Background</h3> Those affected by advanced fibrotic interstitial lung diseases (ILDs) have considerable unmet symptom and psychological needs. Case conferencing has been proposed to address these issues, but requires evaluation. <h3>Aim</h3> To obtain preliminary information on the impact of a case conference intervention delivered in the home (Hospital2Home) on palliative care concerns of patients and their carers, and to evaluate feasibility and acceptability. <h3>Methods</h3> Hospital2Home was trialled at a specialist centre using a Phase II fast-track randomised controlled trial with qualitative interviews. The primary outcome for effect was mean change from baseline of Palliative Care Outcome Scale (POS) (a measure of symptoms and concerns) at 4 weeks. Secondary outcomes included symptom control, quality of life, consent and recruitment rates and percentage of patients in the fast-track group receiving case conferences within 14 days. <h3>Results</h3> 53 patients were recruited (26 fast-track, 27 controls). Mean (SD) POS scores at 4 weeks were −5.7 (7.5) fast-track vs −0.4 (8.0) control, (mean change difference between the two arms was −5.3 (95% CI −9.8 to −0.7) independent t test p=0.02); effect size (95% CI) −0.7 (−1.2 to −0.1). The secondary outcomes of quality of life, anxiety and depression were superior in the fast-track arm, and none were worse. Qualitative findings corroborate these data. Recruitment was successful and 53/67 (79%) of eligible patients consented. 6/25 (24%) had case conferences within 14 days. <h3>Conclusions</h3> Community case conferences improve palliative symptoms and quality of life after 4 weeks. Hospital2Home for the most part is both feasible and acceptable. It now requires further testing in multicentre trials. <h3>Trial registration number</h3> NCT01450644
IL-15 is an inflammatory mediator in the tumor microenvironment
Authors: Scott M Anthony, Gabriel Pham, Kimberly S Schluns
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Previous studies have shown that activation of the Stimulator of Interferon Genes (STING) pathway is important for regulating type I Interferons (IFN) in tumors. Furthermore, tumor DNA induces IL-15 and IL-15Rα mRNA in cultured dendritic cells (DC) in a STING-dependent manner.
Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients.
Authors: M C Etienne, G Milano, M Frenay, N Renee, E Francois, A Thyss, M Schneider, M Namer
Journal: Journal of Clinical Oncology (1992)

PURPOSE Medroxyprogesterone acetate (MPA) is one of the major drugs used in endocrine therapy for advanced breast cancer. However, its optimal dose still has not been clearly established. Response to treatment and drug-related side effects were analyzed as a function of plasma MPA concentrations during prolonged MPA treatment. PATIENTS AND METHODS MPA plasma concentrations were measured (high-performance liquid chromatography [HPLC] assay) at steady state (Css min) in 129 patients (mean age, 63 years; range, 34 to 87) treated by MPA (86% were treated orally exclusively with daily doses ranging from 400 to 2,000 mg). RESULTS A wide interpatient variability was noted in MPA Css min for the 70 patients who received 1,000 mg/d orally (median, 51 ng/mL; range, 10 to 269 ng/mL). Intrapatient analysis of the evolution of MPA Css min during prolonged treatment showed relative stability of MPA concentrations (mean CV, 20.6%). A weak but significant correlation was demonstrated between oral doses and MPA Css min (P = .016). Thirty-five percent of patients (45 of 129) developed MPA-related side effects that were associated with the highest plasma MPA concentrations; medians were 81 and 32 ng/mL for toxic and nontoxic treatments, respectively (P less than .001). Objective response was assessable in 55 patients who were treated by MPA exclusively. Plasma MPA concentrations were significantly different (P = .025) between patients with progressive disease (PD) (median, 46 ng/mL) and those with complete response (CR), partial response (PR), or stable disease (SD) (median 65 ng/mL). Comparison of CR plus PR versus SD versus PD showed only a tendency toward significant differences in MPA Css min (P = .07). Analysis of toxicity and response as a function of the oral dose did not show any significant relationship. These data suggested an optimal therapeutic window for MPA Css min located within 50 to 70 ng/mL. CONCLUSION This study demonstrates that plasma MPA concentration, as opposed to the administered dose, is a determining factor for toxicity and response therapy [corrected].
Altered von Willebrand factor molecule in children with thrombosis following asparaginase-prednisone-vincristine therapy for leukemia.
Authors: C H Pui, C M Chesney, J Weed, C W Jackson
Journal: Journal of Clinical Oncology (1985)

Eleven consecutive leukemia patients with thrombosis induced by asparaginase-prednisone-vincristine therapy were studied to gain insight into the pathogenesis of this complication. Measurement of anti-thrombin III, plasminogen, factor V, and fibrin degradation products as well as platelet aggregation sensitivity to adenosine diphosphate disclosed no consistent abnormalities that would explain pathologic thrombus formation. A decrease in platelet counts observed in nine of 11 patients, prompted us to investigate the possible involvement of factor VIII in this disorder. Levels of factor VIII procoagulant activity, von Willebrand factor (vWF) and ristocetin cofactor were similar to findings for an identically treated comparison group who remained free of thrombotic complications. However, qualitative examination of vWF by crossed immunoelectrophoresis (CIE) revealed a distinct right shift of the immunoprecipitin lines in each of three thrombotic patients tested, whereas a normal profile was found in three similarly treated patients without the complication. This altered pattern had reverted to normal when CIE was repeated 2 to 7 months later. We postulate that the abnormal vWF is related to the development of thrombosis.
<i>Drosophila</i>X-Linked Genes Have Lower Translation Rates than Autosomal Genes
Authors: Zhenguo Zhang, Daven C. Presgraves
Journal: Molecular Biology and Evolution (2015)

In Drosophila, X-linked and autosomal genes achieve comparable expression at the mRNA level. Whether comparable X-autosome gene expression is realized at the translational and, ultimately, the protein levels is, however, unknown. Previous studies suggest the possibility of higher translation rates for X-linked genes owing to stronger usage of preferred codons. In this study, we use public ribosome profiling data from Drosophila melanogaster to infer translation rates on the X chromosome versus the autosomes. We find that X-linked genes have consistently lower ribosome densities than autosomal genes in S2 cells, early embryos, eggs, and mature oocytes. Surprisingly, the lower ribosome densities of X-linked genes are not consistent with faster translation elongation but instead imply slower translation initiation. In particular, X-linked genes have sequence features known to slow translation initiation such as stronger mRNA structure near start codons and longer 5′-UTRs. Comparison to outgroup species suggests that stronger mRNA structure is an evolved feature of Drosophila X chromosomes. Finally, we find that the magnitude of the X-autosome difference in ribosome densities is smaller for genes encoding members of protein complexes, suggesting that stoichiometry constrains the evolution of translation rates. In sum, our analyses suggest that Drosophila X-linked genes have evolved lower translation rates than autosomal genes despite stronger usage of preferred codons.
Extrarenal Progenitor Cells Do Not Contribute to Renal Endothelial Repair
Authors: Jan Sradnick, Song Rong, Anika Luedemann, Simon P. Parmentier, Christoph Bartaun, Vladimir T. Todorov, Faikah Gueler, Christian P. Hugo, Bernd Hohenstein
Journal: Journal of the American Society of Nephrology (2015)

Endothelial progenitor cells (EPCs) may be relevant contributors to endothelial cell (EC) repair in various organ systems. In this study, we investigated the potential role of EPCs in renal EC repair. We analyzed the major EPC subtypes in murine kidneys, blood, and spleens after induction of selective EC injury using the concanavalin A/anti-concanavalin A model and after ischemia/reperfusion (I/R) injury as well as the potential of extrarenal cells to substitute for injured local EC. Bone marrow transplantation (BMTx), kidney transplantation, or a combination of both were performed before EC injury to allow distinction of extrarenal or BM-derived cells from intrinsic renal cells. During endothelial regeneration, cells expressing markers of endothelial colony-forming cells (ECFCs) were the most abundant EPC subtype in kidneys, but were not detected in blood or spleen. Few cells expressing markers of EC colony-forming units (EC-CFUs) were detected. In BM chimeric mice (C57BL/6 with tandem dimer Tomato-positive [tdT+] BM cells), circulating and splenic EC-CFUs were BM-derived (tdT+), whereas cells positive for ECFC markers in kidneys were not. Indeed, most BM-derived tdT+ cells in injured kidneys were inflammatory cells. Kidneys from C57BL/6 donors transplanted into tdT+ recipients with or without prior BMTx from C57BL/6 mice were negative for BM-derived or extrarenal ECFCs. Overall, extrarenal cells did not substitute for any intrinsic ECs. These results demonstrate that endothelial repair in mouse kidneys with acute endothelial lesions depends exclusively on local mechanisms.
Massive benzodiazepine requirements during acute alcohol withdrawal
Authors: E Woo, D J Greenblatt
Journal: American Journal of Psychiatry (1979)

Severe alcohol withdrawal developed in an abstinent chronic alcoholic man. Massive doses of benzodiazepines (2,335 mg of diazepam intravenously, 21,225 mg of oxazepam orally) achieved only marginal control of delirium and agitation. Analysis of multiple blood samples drawn during and after the withdrawal episode indicated, as expected, very high concentrations of diazepam and metabolites and of oxazepam. There was no evidence of an abnormal pharmacokinetic profile. Benzodiazepine resistance in withdrawing alcoholics probably reflects a receptor-site phenomenon rather than an abnormal drug disposition.