bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulating the Epigenome in Germinal Center Lymphomas: Is It Getting Easier and EZier?
Authors: Amengual Jennifer E. , O'Connor Owen A. 
Published: May 2014

Abstract
Mutations affecting key epigenetic modifiers tend to cluster in malignancies in which cells of origin lie in the germinal center (GC). EZH2, as transcriptional repressor, is mutated in high frequency in Chinese and Western patients with follicular lymphoma and may represent a rational target for GC-derived lymphomas. Clin Cancer Res; 20(12); 3047–9. ©2014 AACR.
Targeting Mitochondrial Metabolism by Inhibiting Autophagy in BRAF-Driven Cancers
Authors: Strohecker Anne M. , White Eileen 
Published: May 2014

Abstract
Metabolomic analyses of human tumors and mouse models of cancer have identified key roles for autophagy in supporting mitochondrial metabolism and homeostasis. In this review, we highlight data suggesting that autophagy inhibition may be particularly effective in BRAF-driven malignancies. Catalytic BRAF inhibitors have profound efficacy in tumors carrying activating mutations in Braf but are limited by the rapid emergence of resistance due in part to increased mitochondrial biogenesis and heightened rates of oxidative phosphorylation. We suggest that combined inhibition of autophagy and BRAF may overcome this limitation.
Significance: Braf V600E-driven tumors require autophagy and likely autophagy-provided substrates to maintain mitochondrial metabolism and to promote tumor growth, suggesting that autophagy ablation may improve cancer therapy. Cancer Discov; 4(7); 766–72. ©2014 AACR.
Ablation of Epicardial Ganglionated Plexi Increases Atrial Vulnerability to Arrhythmias in Dogs
Authors: Mao Jun , Yin Xiandong , Zhang Ying , Yan Qian , Dong Jianzeng , Ma Changsheng , Liu Xingpeng 
Published: May 2014

Background—
Previous studies have suggested that systematic ablation of ganglionated plexi (GP) could increase the short-term success rate of radiofrequency ablation for atrial fibrillation, but the long-term efficacy of this approach is not fully established.

Methods and Results—
Twenty-four mongrel dogs were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial GP ablation group 2 (n=8), and a sham operation group (n=8). In the 2 epicardial GP ablation groups, the 4 major GP and the ligament of Marshall were systematically ablated. The effective refractory period and inducibility of tachyarrhythmias were measured before and immediately after GP ablation in epicardial GP ablation group 1 and 8 weeks later in the other 2 groups. Tyrosine hydroxylase and choline acetyltransferase expressions were also determined immunohistochemically 8 weeks later in the latter groups. Compared with epicardial GP ablation group 1 and the sham operation group, epicardial GP ablation group 2 had the shortest atrial and ventricular effective refractory period and the highest inducibility of atrial tachyarrhythmias. The inducibility of ventricular tachyarrhythmias among the 3 groups was comparable. The density of tyrosine hydroxylase– and choline acetyltransferase–positive nerves in the atrium was the highest in epicardial GP group 2, whereas there were no significant intergroup differences in the densities of these 2 types of nerves in the ventricle.

Conclusions—
After 8 weeks of healing, epicardial GP ablation without additional atrial ablation was potentially proarrhythmic, which may be attributable to decreased atrial effective refractory period and hyper-reinnervation involving both sympathetic and parasympathetic nerves.
Perceived Stigma Among People With Chronic Health Conditions
Authors: Brown Robyn Lewis 
Published: May 2014

Objectives: This study addresses whether age, functional limitation and other stressor exposure, and psychosocial coping resources influence variation in perceived stigma and the form this influence takes (i.e., independent and/or interdependent). Methods: Using data from two waves of a large community study of adults (age 20–93) with chronic health conditions ( n = 417), a residual change regression analysis considers direct and moderating factors influencing perceived stigma over a 3-year period. Results: Age, functional limitation, the experience of discrimination, and self-esteem independently account for variation in perceived stigma. Moderation tests reveal that age is associated with a greater increase in stigma in the context of greater functional limitation and increases in limitation. Functional limitation and stressor exposure are also associated with declines in stigma in the context of greater mastery and self-esteem. Discussion: Multiple processes bear on perceived stigma among people with chronic health conditions. Implications for stigma and stress research are discussed.
Evidence-based use of FFP: the influence of a priming strategy without FFP during CPB on postoperative coagulation and recovery in pediatric patients
Authors: Miao X , Liu J , Zhao M , Cui Y , Feng Z , Zhao J , Long C , Li S , Yan F , Wang X , Hu S 
Published: May 2014

Objective: Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP. Method: Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected. Results: After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups. Conclusion: In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients.
The Effect of Smoking on Rotator Cuff and Glenoid Labrum Surgery
Authors: Santiago-Torres Juan , Flanigan David C. , Butler R. Bryan , Bishop Julie Y. 
Published: May 2014

Background: Several orthopaedic conditions have been reported to be adversely affected by smoking. Only a few studies have looked at outcomes related to smoking in shoulder surgery. Purpose/Hypothesis: To determine whether smoking has a negative influence on tendinous, ligamentous, and cartilaginous shoulder surgery. The hypothesis was that smoking has a negative influence from both a basic science and clinical outcomes perspective on soft tissue shoulder surgery. Study Design: Systematic review. Methods: A systematic review of multiple medical databases was performed evaluating clinical outcomes and basic science studies to determine the effects of smoking on tendinous, ligamentous, and cartilaginous shoulder surgery. The search strategy was based on “shoulder AND [smoke OR smoking OR nicotine OR tobacco].” English language clinical outcomes or basic science studies following soft tissue surgery of the shoulder were included. Studies excluded consisted of those with evidence level 5, partial or total shoulder arthroplasty, fracture reduction and fixation, oncologic mass excision, and osteotomy around the shoulder. Results: Ten studies were identified for inclusion and analysis. Eight of these studies, which included 1 basic science study, investigated the relationship between smoking and outcomes of rotator cuff repair (RCR), and 2 examined the effects of smoking on outcomes of glenoid labrum repair. No studies were found that specifically explored the effects of smoking on cartilaginous shoulder surgery. The basic science study and 3 of the 7 clinical outcomes studies investigating smoking and rotator cuff (RTC) surgery outcomes found a statistically significant negative association resulting in decreased RTC tendon repair quality, decreased biomechanics, poorer clinical outcomes, and impaired healing of small-medium RTC tears as assessed by magnetic resonance imaging. In addition, 1 of 2 clinical outcomes studies examining smoking and glenoid labrum repair reported an increased need for surgical revision of superior labral anterior to posterior (SLAP) tears in smokers. No basic science studies were found that investigated the effects of smoking on glenoid labrum surgery. Conclusion: Smoking has a negative influence on RCR clinical outcomes and is associated with decreased healing of small-medium RTC tears after repair. The current literature suggests a negative influence of nicotine and smoking on RCR from both a basic science and clinical outcomes perspective. Smoking cessation would benefit patients undergoing RCR and improve clinical outcomes. The relationship of smoking and labral/SLAP repair or articular cartilage is less clear. Further research is needed to evaluate associations with these surgeries and outcomes. Clinical Relevance: Smoking has a negative influence on RCR clinical outcomes and is associated with decreased healing of small-medium RTC tears after repair.
How Youth-Serving Organizations Enable Acquaintance Molesters
Authors: Boyle Patrick 
Published: May 2014

In recent years, some of the country’s most prominent institutions have been ensnared in child sex abuse scandals. While each abuse incident features its own particular circumstances, institutions that have been the subject of these scandals have displayed similar patterns of organizational behavior that allowed molesting to occur and molesters to escape accountability. We can learn from those patterns to better understand and combat acquaintance molestation in youth-serving organizations. Although sex abuse is an inherent risk in youth work, American youth-serving organizations have responded to this risk largely on a case-by-case basis after abuse incidents have been revealed, rather than through proactive strategies to reduce the risk of abuse and to respond effectively to allegations. An examination of abuse scandals reveals common patterns of behavior among paid and volunteer staff in organizations that did not enact comprehensive, proactive strategies: Faith in the organiation blinded staff to the liklihood of abuse; organizations kept workers ignorant about the extent of the abuse problem; when abuse accusations arose, staff gave the benefit of the doubt to the adult; when abuse accusations were confirmed, staffers did not know how to respond; and not knowing how to resopnd, staff prioritized the protection of the organization. As a result, child molesters have been falsely exonerated or not held accountable, abused children have been disbelieved, and abuse has continued. These organizations inadvertently achieved the opposite of their missions: They enabled child molesters at the expense of children.
Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes
Authors: Scully Marie , Thomas Mari , Underwood Mary , Watson Henry , Langley Katherine , Camilleri Raymond S. , Clark Amanda , Creagh Desmond , Rayment Rachel , Mcdonald Vickie , Roy Ashok , Evans Gillian , McGuckin Siobhan , Ni Ainle Fionnuala , Maclean Rhona , Lester William , Nash Michael , Scott Rosemary , O Brien Patrick ,   collaborators of the UK TTP Registry
Published: May 2014

Key Points
In women presenting with an initial diagnosis of TTP during pregnancy, cTTP was more common than acquired TTP. Active monitoring and management during pregnancy results in positive pregnancy outcomes.
Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study
Authors: Abrahamsson Anna , Albertsson-Lindblad Alexandra , Brown Peter N. , Baumgartner-Wennerholm Stefanie , Pedersen Lars M. , D’Amore Francesco , Nilsson-Ehle Herman , Jensen Paw , Pedersen Michael , Geisler Christian H. , Jerkeman Mats 
Published: May 2014

Key Points
Rituximab and autologous stem cell transplantation are both independently associated with improved overall survival in mantle cell lymphoma. Male gender is an independent negative prognostic factor in mantle cell lymphoma.
Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia
Authors: Treon Steven P. , Tripsas Christina K. , Meid Kirsten , Kanan Sandra , Sheehy Patricia , Chuma Stacey , Xu Lian , Cao Yang , Yang Guang , Liu Xia , Patterson Christopher J. , Warren Diane , Hunter Zachary R. , Turnbull Barry , Ghobrial Irene M. , Castillo Jorge J. 
Published: May 2014

Key Points
Carfilzomib, rituximab, and dexamethasone (CaRD) produce overall and CR/VGPR responses in 87% and 36% of frontline WM patients, respectively. CaRD activity was not impacted by MYD88 and CXCR4 mutations and represents a neuropathy-sparing option for treating WM patients.
Prevalence of gastrointestinal stromal tumour (GIST) in the United Kingdom at different therapeutic lines: an epidemiologic model
Authors: Starczewska Amelio Justyna M , Cid Ruzafa Javier , Desai Kamal , Tzivelekis Spiros , Muston Dominic , Khalid Javaria Mona , Ashman Philip , Maguire Andrew 
Published: May 2014

Abstract

Background
The prevalence of patients with gastrointestinal stromal tumourgst (GIST) who fail currently available treatments imatinib and sunitinib (third-line treatment-eligible GIST) is unknown, but is expected to be below an ultra-orphan disease threshold of 2/100,000 population used in England and Wales. Our study was designed to estimate the prevalence and absolute number of UK patients with unresectable/metastatic GIST at first-, second- and eventually third-line treatment.

Methods
Our open population model estimates the probability that the prevalence of UK third-line treatment-eligible GIST patients will remain under the ultra-orphan disease threshold. Model parameters for incidence, proportion of unresectable/metastatic disease and survival estimates for GIST patients were obtained from a targeted literature review and a UK cancer register. The robustness of the results was checked through differing scenarios taking extreme values of the input parameters.

Results
The base-case scenario estimated a prevalence of third-line treatment-eligible GIST of 1/100,000 and a prevalence count of 598 with a 99.9% likelihood of being below the ultra-orphan disease threshold. The extreme scenarios, one-way and probabilistic sensitivity analyses and threshold analysis confirmed the robustness of these results.

Conclusions
The prevalence of third-line treatment-eligible GIST is very low and highly likely below the ultra-orphan disease threshold.
Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells
Authors: Hirschi Benjamin , Gallmeier Eike , Ziesch Andreas , Marschall Maximilian , Kolligs Frank T 
Published: May 2014

Abstract

Background
Colorectal cancers carrying the B-Raf V600E-mutation are associated with a poor prognosis. The purpose of this study was to identify B-RafV600E-mediated traits of cancer cells in a genetic in vitro model and to assess the selective sensitization of B-RafV600E-mutant cancer cells towards therapeutic agents.

Methods
Somatic cell gene targeting was used to generate subclones of the colorectal cancer cell line RKO containing either wild-type or V600E-mutant B-Raf kinase. Cell-biologic analyses were performed in order to link cancer cell traits to the BRAF-mutant genotype. Subsequently, the corresponding tumor cell clones were characterized pharmacogenetically to identify therapeutic agents exhibiting selective sensitivity in B-RafV600E-mutant cells.

Results
Genetic targeting of mutant BRAF resulted in restoration of sensitivity to serum starvation-induced apoptosis and efficiently inhibited cell proliferation in the absence of growth factors. Among tested agents, the B-Raf inhibitor dabrafenib was found to induce a strong V600E-dependent shift in cell viability. In contrast, no differential sensitizing effect was observed for conventional chemotherapeutic agents (mitomycin C, oxaliplatin, paclitaxel, etoposide, 5-fluorouracil), nor for the targeted agents cetuximab, sorafenib, vemurafenib, RAF265, or for inhibition of PI3 kinase. Treatment with dabrafenib efficiently inhibited phosphorylation of the B-Raf downstream targets Mek 1/2 and Erk 1/2.

Conclusion
Mutant BRAF alleles mediate self-sufficiency of growth signals and serum starvation-induced resistance to apoptosis. Targeting of the BRAF mutation leads to a loss of these hallmarks of cancer. Dabrafenib selectively inhibits cell viability in B-RafV600E mutant cancer cells.
Secondary bile acids: an underrecognized cause of colon cancer
Authors: Ajouz Hana , Mukherji Deborah , Shamseddine Ali 
Published: May 2014

Abstract
Bile acids were first proposed as carcinogens in 1939. Since then, accumulated evidence has linked exposure of cells of the gastrointestinal tract to repeated high physiologic levels of bile acids as an important risk factor for gastrointestinal cancers. High exposure to bile acids may occur in a number of settings, but most importantly, is prevalent among individuals who have a high dietary fat intake.
A rapid effect on cells of high bile acid exposure is the generation of reactive oxygen species and reactive nitrogen species, disruption of the cell membrane and mitochondria, induction of DNA damage, mutation and apoptosis, and development of reduced apoptosis capability upon chronic exposure. Here, we review the substantial evidence of the mechanism of secondary bile acids and their role in colon cancer.
Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study
Authors: Kura Aminu Umar , Cheah Pike-See , Hussein Mohd Zobir , Hassan Zurina , Tengku Azmi Tengku Ibrahim , Hussein Nor Fuzina , Fakurazi Sharida 
Published: May 2014

Abstract
Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.
Generalized MMSE beamforming for multicell MIMO systems with random user geometry and channel feedback latency
Authors: Sohn Illsoo , Lee Hyoungjoo , Lee Kwang Bok 
Published: May 2014

Abstract
In this paper, we propose a generalized minimum mean square error (MMSE) beamforming for downlink multicell multiple-input multiple-output (MIMO) systems with local BS cooperations. Unlike the previous beamforming strategies which have been designed for an idealized multicell MIMO system model, we consider a complicated but realistic multicell MIMO system model. Our realistic multicell MIMO system model captures (i) different average SNRs of users due to random geometrical distribution of users within cells, (ii) channel feedback latency due to air propagation time and signal processing time, and (iii) different channel aging effects for intracell channel information and intercell channel information due to an additional backhaul latency during the exchange of information between pairs of neighboring cells. The key novelty of this paper is that we derive the closed-form beamforming expressions of the generalized MMSE beamforming using convex optimization technique. The closed-form beamforming expression gives insights on how the geometry of users and channel feedback latency affect the construction of optimal beamforming vectors. Numerical results verify that the proposed generalized MMSE beamforming outperforms previous beamforming strategies in both BER and average throughput performances.
Occurrence of Vibrio and Salmonella species in mussels (Mytilus galloprovincialis) collected along the Moroccan Atlantic coast
Authors: Mannas Hasna , Mimouni Rachida , Chaouqy Noureddine , Hamadi Fatima , Martinez-Urtaza Jaime 
Published: May 2014

Abstract
This study reports the occurrence of different Vibrio and Salmonella species in 52 samples of Mytilus galloprovincialis collected from four sites along the Atlantic coast between Agadir and Essaouira (Anza, Cap Ghir, Imssouane and Essaouira). The level of Escherichia coli (E. coli) was also determined to evaluate the degree of microbial pollution in the investigated areas. In this study three methods were used : AFNOR NF EN ISO 6579 V08-013 for Salmonella spp., the provisional method routinely used by several laboratories (Institut Pasteur, Paris,…) for Vibrio cholerae and Vibrio parahaemolyticus in the seafood, and the most probable number method (MPN) using Norm ISO/TS 16649–3 (2005) for E. coli. The most frequently isolated Vibrios were Vibrio alginolyticus (90.4% of samples), followed by V. cholerae non O1 non O139 (15.4%) and V. parahaemolyticus (7.7%). Salmonella spp. was found in 15% of the samples. The number of E. coli ranged between 0.2/100 g and 1.8 103 /100 g of mussel soft tissues. This study indicates the potential sanitary risk associated with the presence of pathogenic bacteria in cultivated mussels in the two populous regions of southern Morocco, where shellfish production and maritime tourism are important to the local economy.