bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Therapeutic Efficacy of a Novel Pharmacologic Inducer of Apoptosis in Malignant Peripheral Nerve Sheath Tumors
Authors: Chau Vincent , Lim S. Kyun , Mo Wei , Liu Chiachi , Patel Amish J. , McKay Renée M. , Wei Shuguang , Posner Bruce A. , De Brabander Jef K. , Williams Noelle S. , Parada Luis F. , Le Lu Q. 
Published: November 2013

AbstractNeurofibromatosis type I (NF1) is an autosomal disorder that affects neural crest-derived tissues, leading to a wide spectrum of clinical presentations. Patients commonly present with plexiform neurofibromas, benign but debilitating growths that can transform into malignant peripheral nerve sheath tumors (MPNST), a main cause of mortality. Currently, surgery is the primary course of treatment for MPNST, but with the limitation that these tumors are highly invasive. Radiotherapy is another treatment option, but is undesirable because it can induce additional mutations. Patients with MPNST may also receive doxorubicin as therapy, but this DNA-intercalating agent has relatively low tumor specificity and limited efficacy. In this study, we exploited a robust genetically engineered mouse model of MPNST that recapitulates human NF1-associated MPNST to identify a novel small chemical compound that inhibits tumor cell growth. Compound 21 (Cpd21) inhibits growth of all available in vitro models of MPNST and human MPNST cell lines, while remaining nontoxic to normally dividing Schwann cells or mouse embryonic fibroblasts. We show that this compound delays the cell cycle and leads to cellular apoptosis. Moreover, Cpd21 can reduce MPNST burden in a mouse allograft model, underscoring the compound's potential as a novel chemotherapeutic agent. Cancer Res; 74(2); 586–97. ©2013 AACR.
Blocking Lactate Export by Inhibiting the Myc Target MCT1 Disables Glycolysis and Glutathione Synthesis
Authors: Doherty Joanne R. , Yang Chunying , Scott Kristen E.N. , Cameron Michael D. , Fallahi Mohammad , Li Weimin , Hall Mark A. , Amelio Antonio L. , Mishra Jitendra K. , Li Fangzheng , Tortosa Mariola , Genau Heide Marika , Rounbehler Robert J. , Lu Yunqi , Dang Chi V. , Kumar K. Ganesh , Butler Andrew A. , Bannister Thomas D. , Hooper Andrea T. , Unsal-Kacmaz Keziban , Roush William R. , Cleveland John L. 
Published: November 2013

Abstract
Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here, we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1 and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, reductions in glucose transport, and in levels of ATP, NADPH, and ultimately, glutathione (GSH). Reductions in GSH then lead to increases in hydrogen peroxide, mitochondrial damage, and ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies. Cancer Res; 74(3); 908–20. ©2013 AACR.
Targeting Epithelial-to-Mesenchymal Transition with Met Inhibitors Reverts Chemoresistance in Small Cell Lung Cancer
Authors: Cañadas Israel , Rojo Federico , Taus Álvaro , Arpí Oriol , Arumí-Uría Montserrat , Pijuan Lara , Menéndez Silvia , Zazo Sandra , Dómine Manuel , Salido Marta , Mojal Sergi , García de Herreros Antonio , Rovira Ana , Albanell Joan , Arriola Edurne 
Published: November 2013

Abstract
Purpose: Met receptor phosphorylation is associated with poor prognosis in human small cell lung cancer (SCLC). The aim of our work was to investigate the effects of hepatocyte growth factor (HGF)/Met–mediated epithelial-to-mesenchymal transition (EMT) in SCLC and to evaluate the role of Met inhibition in mesenchymal/chemorefractory SCLC models.
Experimental Design: SCLC models of HGF-induced EMT were evaluated in vitro and in vivo (subcutaneous xenografts in BALB/c nude mice) for chemosensitivity and response to Met inhibition with PF-2341066 (crizotinib). Human SCLC samples at diagnosis (N = 87) and relapse (N = 5) were evaluated by immunohistochemistry and immunofluorescence for EMT markers and Met status and these were correlated with patient outcome.
Results: We identified that the activation of the Met receptor through HGF induced expression of mesenchymal markers, an aggressive phenotype, and chemoresistance. Blockade of this process with the Met inhibitor resensitized cells to chemotherapy in vitro and in vivo. Moreover, mesenchymal markers in human SCLC specimens were associated with Met activation, predicted worse survival, and were upregulated in chemorefractory disease.
Conclusion: These results provide novel evidence on an important role of Met-dependent EMT in the adverse clinical behavior of SCLC and support clinical trials of Met inhibitors and chemotherapy in this fatal disease. Clin Cancer Res; 20(4); 938–50. ©2013 AACR.
Cabozantinib and Prostate Cancer: Inhibiting Seed and Disrupting Soil?
Authors: Lee Richard J. , Smith Matthew R. 
Published: November 2013

Abstract
Treatment with cabozantinib, an inhibitor of MET and VEGFR2 signaling, has demonstrated clinical benefit in early trials in men with metastatic prostate cancer. Preclinical evidence suggests that cabozantinib can kill cancer cell seeds while disrupting angiogenesis and stromal cells in the metastatic soil. Clin Cancer Res; 20(3); 525–7. ©2013 AACR.
Medical literature, vena cava filters and evidence of efficacy
Authors: Meyer Guy , Parent Florence , Mismetti Patrick , Girard Philippe 
Published: November 2013

SummaryUp to 15% of all patients with venous thromboembolism (VTE) receive an inferior vena cava filter, and prophylactic placements are increasing. To determine whether current use of filters is based on robust evidence, a global review of the recent (2001–2012) literature on filters was undertaken. The MEDLINE database was searched for articles related to filters appearing during the period 2001–2012, updating a prior search of literature from 1975–2001. All retrieved articles were analysed, classified into predetermined categories and compared to the prior analysis; randomised and large (>100 patients with a filter) comparative non-randomised clinical studies were read in full. The 651 articles, vs 568 in the period 1975–2000, consisted mainly of retrospective series (37.8%), case reports (31.7%), reviews (14.7%, vs 6.7%, p<0.001), animal and/or in vitro studies (7.5%, vs 12.9%, p=0.002), and prospective series or trials (4.9%, vs 7.4%, p=0.07). Of 4 new randomised trials (RCT), none were designed to test the efficacy of the device; to date, only one RCT has attempted to ascertain efficacy, occurring during the period 1975–2000. Eleven large non-randomised studies compared clinical outcomes of patients with and without filters, in VTE patients (n=5) or prophylactic indications (n=6); two studies found statistically significant relationships between filter use and lower mortality rates, though none could demonstrate a causal relationship. Hence, the plethoric literature on filters parallels growing experience with these devices, but still fails to provide reliable evidence that filter use improves relevant clinical outcomes. No indication for filter placement is based on appropriate scientific evidence.
Update on selective treatments targeting neutrophilic inflammation in atherogenesis and atherothrombosis
Authors: Quinderé Ana Luíza Gomes , Benevides Norma Maria Barros , Carbone Federico , Mach François , Vuilleumier Nicolas , Montecucco Fabrizio 
Published: November 2013

SummaryAtherosclerosis is the most common pathological process underlying cardiovascular diseases. Current therapies are largely focused on alleviating hyperlipidaemia and preventing thrombotic complications, but do not completely eliminate risk of suffering recurrent acute ischaemic events. Specifically targeting the inflammatory processes may help to reduce this residual risk of major adverse cardiovascular events in atherosclerotic patients. The involvement of neutrophils in the pathophysiology of atherosclerosis is an emerging field, where evidence for their causal contribution during various stages of atherosclerosis is accumulating. Therefore, the identification of neutrophils as a potential therapeutic target may offer new therapeutic perspective to reduce the current atherosclerotic burden. This narrative review highlights the expanding role of neutrophils in atherogenesis and discusses on the potential treatment targeting neutrophil-related inflammation and associated atherosclerotic plaque vulnerability.
Unanswered questions and research priorities to optimise stroke prevention in atrial fibrillation with the new oral anticoagulants
Authors: Hankey Graeme J. 
Published: November 2013

SummaryThis review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can “cut-off points” between which anticoagulation is therapeutic (i.e. the “therapeutic range”) be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?
Changes in Ultrasound-Assessed Carotid Intima-Media Thickness and Plaque With a Mediterranean Diet
Authors: Sala-Vila Aleix , Romero-Mamani Edwin-Saúl , Gilabert Rosa , Núñez Isabel , de la Torre Rafael , Corella Dolores , Ruiz-Gutiérrez Valentina , López-Sabater María-Carmen , Pintó Xavier , Rekondo Javier , Martínez-González Miguel-Ángel , Estruch Ramon , Ros Emilio 
Published: November 2013

Objective—
The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk.

Approach and Results—

In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [−0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (−0.084 mm [−0.158 to −0.010 mm];
P
=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, −0.030 mm [−0.153 to 0.093 mm];
P
=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, −0.091 mm [−0.206 to 0.023 mm];
P
=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil.

Conclusions—
Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN35739639.
Outcome of mood disorders before psychopharmacology: A systematic review
Authors: Mulder Roger T , Frampton Christopher MA 
Published: November 2013

Objectives: This paper systematically reviews all outcome studies of patients with mood disorders treated prior to the widespread use of antidepressants, mood stabilizers, and major tranquillizers. The aim is to estimate recovery and sustained recovery rates and to provide some evidence about the efficacy of modern drug treatments in changing the long-term outcome of mood disorders. Methods: MEDLINE and PSYCHINFO searches for studies on mood disorders published prior to 1970 were performed. Most studies were obtained by hand searching and extensive cross referencing. Information was independently extracted by the two authors. Results: A total of 29 relevant articles were obtained. The studies reviewed over 14,000 patients in total. Patients were mainly inpatients with a predominance of females. The majority of patients suffered from depression. The cohorts were followed up for 1–30 years. The median rate of recovery was 69% (range 17–91%). The time to recovery was generally several months. The median rate of recovering and remaining well was 51% (range 21–67%). Conclusions: The median rate of recovery is less than modern cohorts and the time to recovery longer. However, the rate of recovering and remaining well appears high compared to modern cohorts, although this result may reflect methodological issues. This review provides no support to the belief that pharmacological treatments have resulted in an improvement in the long-term outcome of patients with mood disorders.
Anthropology of Islam: History, culture and power
Authors: Ahmad Irfan 
Published: November 2013

NILE GREEN, BOMBAY ISLAM: The Religious Economy of the West Indian Ocean, 1840–1915 (Cambridge: Cambridge University Press), 2011, pp. 327 HUMEIRA IQTIDAR, SECULARIZING ISLAMISTS? Jama’at-e-Islami and Jama’at-ud-da’wa in Urban Pakistan (Ranikhet: Permanent Black), 2011, pp. 216.
Lymphocyte sensitivity assay as a marker for glucocorticoid resistance in lupus: report of two sisters with systemic lupus erythematosus
Authors: Fajardo-Hermosillo LD , Rodríguez-Navedo Y , Nadal AJ , Vilá LM 
Published: November 2013

Glucocorticoid sensitivity can be measured in vitro using the lymphocyte sensitivity assay (LSA). In this test, dexamethasone is used to inhibit the proliferation of peripheral blood mononuclear cells (PBMC) in response to mitogens. If the proliferation of PBMC is suppressed the subjects are considered to be GC sensitive; if not, they are considered to be resistant. The LSA has been used to test GC sensitivity in some inflammatory diseases but its clinical value in systemic lupus erythematosus (SLE) has not been determined. Herein, we present the results of the LSA from two sisters with SLE who had different disease outcomes. Patient 1 presented with higher disease activity and damage accrual, and poorer response to corticosteroids than patient 2. In the LSA, patient 1 had a lower dexamethasone suppression of mitogen-stimulated PBMC than patient 2 and one control subject. The LSA could be helpful in identifying patients with GC resistance, thus allowing the consideration of alternative immunosuppressive drugs.
Discordant minimum inhibitory concentration analysis: A new path to licensure for anti-infective drugs
Authors: Follmann Dean , Brittain Erica , Powers John H 
Published: November 2013

Background Evaluation of anti-infective drugs for licensure often relies on a noninferiority (NI) design where new drug B is noninferior to comparator drug A if the difference in success rates is reliably not worse than some fixed margin. The margin must be based on historical studies that estimate the magnitude of the benefit of drug A over placebo. This approach hampers drug development because the obligatory evidence for margin determination is often nonexistent. Purpose To develop a new method for licensure of anti-infective drugs when there is no historical evidence for reliable construction of the NI margin. Methods The minimum inhibitory concentration (MIC) measures the minimum amount of drug that it takes to inhibit growth of bacteria in vitro. Patients who are infected with bacteria that have a low MIC to a given drug are expected to have good outcomes when treated with that drug. Thus, a differential effect of drug B versus drug A, if it exists, is likely to occur in patients whose pathogens have discordant MICs (e.g., low MIC for drug B, high MIC for drug A, or vice versa). A new paradigm for licensure of anti-infective drugs is proposed where a clinically acceptable NI margin is selected and licensure supported if the NI margin is met and B is reliably demonstrated superior to A in a subset of patients whose paired MICs favor B. The requirement for some evidence of superiority encourages a study that is carefully designed and executed. Results Simulations indicate that the approach shows promise in realistic settings, provided adequate data are available. A simulated example illustrates use of the methods. Limitations If the data have small sample size, weak MIC/success relationship, or high correlation between MIC-A, MIC-B, this procedure will have poor power. Conclusion Discordant MIC analysis may offer a novel path to licensure for certain anti-infective drugs.
Phylogenetic and transcriptional analysis of an expanded bZIP transcription factor family in Phytophthora sojae
Authors: Ye Wenwu , Wang Yang , Dong Suomeng , Tyler Brett M , Wang Yuanchao 
Published: November 2013

Abstract

Background
Basic leucine zipper (bZIP) transcription factors are present exclusively in eukaryotes and constitute one of the largest and most diverse transcription factor families. The proteins are responsible for central developmental and physiological processes in plants, animals, and fungi, including the pathogenicity of fungal plant pathogens. However, there is limited understanding of bZIPs in oomycetes, which are fungus-like organisms in the kingdom Stramenopila. Oomycetes include many destructive plant pathogens, including the well-studied species Phytophthora sojae, which causes soybean stem and root rot.

Results
Candidate bZIPs encoded in the genomes of P. sojae and four other oomycetes, two diatoms, and two fungal species were predicted using bioinformatic methods. Comparative analysis revealed expanded numbers of bZIP candidates in oomycetes, especially the Phytophthora species, due to the expansion of several novel bZIP classes whose highly conserved asparagines in basic DNA-binding regions were substituted by other residues such as cysteine. The majority of these novel bZIP classes were mostly restricted to oomycetes. The large number of novel bZIPs appears to be the result of widespread gene duplications during oomycete evolution. The majority of P. sojae bZIP candidates, including both conventional and novel bZIP classes, were predicted to contain canonical protein secondary structures. Detection of gene transcripts using digital gene expression profiling and qRT-PCR suggested that most of the candidates were not pseudogenes. The major transcriptional shifts of bZIPs occurred during the zoosporangia/zoospore/cyst and host infection stages. Several infection-associated bZIP genes were identified that were positively regulated by H2O2 exposure.

Conclusions
The identification of large classes of bZIP proteins in oomycetes with novel bZIP motif variants, that are conserved and developmentally regulated and thus presumably functional, extends our knowledge of this important family of eukaryotic transcription factors. It also lays the foundation for detailed studies of the roles of these proteins in development and infection in P. sojae and other oomycetes.
Family history of cancer, personal history of medical conditions and risk of oral cavity cancer in France: the ICARE study
Authors: Radoï Loredana , Paget-Bailly Sophie , Guida Florence , Cyr Diane , Menvielle Gwenn , Schmaus Annie , Carton Matthieu , Cénée Sylvie , Sanchez Marie , Guizard Anne-Valérie , Trétarre Brigitte , Stücker Isabelle , Luce Danièle 
Published: November 2013

AbstractBackgroundThe aim of this study was to evaluate the role of family history of cancer and personal history of other medical conditions in the aetiology of the oral cavity cancer in France.MethodsWe used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls included in a population-based case–control study, the ICARE study. Odds-ratios (ORs) associated with family history of cancer and personal medical conditions and their 95% confidence intervals (95% CI) were estimated by unconditional logistic regression and were adjusted for age, gender, area of residence, education, body mass index, tobacco smoking and alcohol drinking.ResultsPersonal history of oral candidiasis was related to a significantly increased risk of oral cavity cancer (OR 5.0, 95% CI 2.1-12.1). History of head and neck cancers among the first-degree relatives was associated with an OR of 1.9 (95% CI 1.2-2.8). The risk increased with the number of first-degree relatives with head and neck cancer.ConclusionA family history of head and neck cancer is a marker of an increased risk of oral cavity cancer and should be taken into account to target prevention efforts and screening. Further studies are needed to clarify the association between oral cavity cancer and personal history of candidiasis.
Surface-exposed proteins of pathogenic mycobacteria and the role of cu-zn superoxide dismutase in macrophages and neutrophil survival
Authors: McNamara Michael , Tzeng Shin-Cheng , Maier Claudia , Wu Martin , Bermudez Luiz E 
Published: November 2013

AbstractPathogenic mycobacteria are important agents causing human disease.Mycobacterium aviumsubsp.hominissuis(M. avium) is a species of recalcitrant environmental pathogen. The bacterium forms robust biofilms that allow it to colonize and persist in austere environments, such as residential and commercial water systems.M. aviumis also an opportunistic pathogen that is a significant source of mortality for immune-compromised individuals. Proteins exposed at the bacterial surface play a central role in mediating the relationship between the bacterium and its environment. The processes underlying both biofilm formation and pathogenesis are directly dependent on this essential subset of the bacterial proteome. Therefore, the characterization of the surface-exposed proteome is an important step towards an improved understanding of the mycobacterial biology and pathogenesis. Here we examined the complement of surface exposed proteins fromMycobacterium avium 104, a clinical isolate and reference strain ofMycobacterium aviumsubsp.hominissuis.To profile the surface-exposed proteins of viableM. avium 104,bacteria were covalently labeled with a membrane impermeable biotinylation reagent and labeled proteins were affinity purified via the biotin-streptavidin interaction. The results provide a helpful snapshot of the surface-exposed proteome of this frequently utilized reference strain ofM. avium.A Cu-Zn SOD knockout mutant, MAV_2043, a surface identified protein, was evaluated regarding its role in the survival in both macrophages and neutrophils.