bluuebunny/crossref_metadata_2025_split huggingface dataset:
State Electoral Institutions and Voter Turnout In Presidential Elections, 1920–2000
Authors: Springer Melanie J. 
Published: May 2012

AbstractExpansiveandrestrictive state electoral institutions have been instrumental in structuring the vote throughout American history. Studies focused on a small number of reforms, years, or states lack the scope necessary to comprehensively evaluate the effects of institutional change over time. This work, however, places recent reforms in historical context and offers a long-term perspective. Using an original data set, it identifies the institutions that have generated the most substantial effects on state turnout rates during presidential elections from 1920 to 2000. Findings demonstrate that restrictive laws (those aiming to limit the vote or make voting more costly) produced large and consistently negative effects in the Southern and non-Southern states alike, but the effects associated with expansive reforms (those making participation more convenient or less costly) vary. Although a few expansive laws have increased turnout in the non-Southern states, they have had no effect in the Southern states where turnout rates are lowest.
Essential role of TAK1 in regulating mantle cell lymphoma survival
Authors: Buglio Daniela , Palakurthi Sangeetha , Byth Kate , Vega Francisco , Toader Dorin , Saeh Jamal , Neelapu Sattva S. , Younes Anas 
Published: May 2012

AbstractTGF-β–activated kinase 1 (TAK1), a member of the MAPK kinase family, plays a key role in B-cell growth and development. In the present study, we examined the potential role of TAK1 as a therapeutic target for lymphoma. Here, we show that the active phosphorylated form of TAK1 is abundantly expressed in a panel of lymphoma cell lines, including mantle cell, anaplastic large cell, and Hodgkin lymphoma cell lines. Silencing TAK1 expression via the use of siRNA inhibited the activation of NF-κB and p38 and induced apoptosis in lymphoma cell lines. Moreover, submicromolar concentrations of AZ-TAK1, a novel ATP-competitive small molecule inhibitor of TAK1, dephosphorylated TAK1, p38, and IκB-α in lymphoma cell lines. These molecular events were associated with the release of cytochrome c into the cytosol, down-regulation of X-linked inhibitor of apoptosis, activation of caspase 9, and induction of apoptosis. We also demonstrate that primary lymphoma cells express TAK1 and pTAK1 and were sensitive to AZ-TAK1–mediated cell death. Collectively, our data demonstrate an essential role for TAK1 in regulating critical survival mechanisms in lymphoma and suggest that it may serve as a therapeutic target.
Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children's Oncology Group
Authors: Loken Michael R. , Alonzo Todd A. , Pardo Laura , Gerbing Robert B. , Raimondi Susana C. , Hirsch Betsy A. , Ho Phoenix A. , Franklin Janet , Cooper Todd M. , Gamis Alan S. , Meshinchi Soheil 
Published: May 2012

AbstractEarly response to induction chemotherapy is a predictor of outcome in acute myeloid leukemia (AML). We determined the prevalence and significance of postinduction residual disease (RD) by multidimensional flow cytometry (MDF) in children treated on Children's Oncology Group AML protocol AAML03P1. Postinduction marrow specimens at the end of induction (EOI) 1 or 2 or at the end of therapy from 249 patients were prospectively evaluated by MDF for RD, and presence of RD was correlated with disease characteristics and clinical outcome. Of the 188 patients in morphologic complete remission at EOI1, 46 (24%) had MDF-detectable disease. Those with and without RD at the EOI1 had a 3-year relapse risk of 60% and 29%, respectively (P < .001); the corresponding relapse-free survival was 30% and 65% (P < .001). Presence of RD at the EOI2 and end of therapy was similarly predictive of poor outcome. RD was detected in 28% of standard-risk patients in complete remission and was highly associated with poor relapse-free survival (P = .008). In a multivariate analysis, including cytogenetic and molecular risk factors, RD was an independent predictor of relapse (P < .001). MDF identifies patients at risk of relapse and poor outcome and can be incorporated into clinical trials for risk-based therapy allocation. This study was registered at www.clinicaltrials.gov as NCT00070174.
Monoclonal antibodies against receptor-induced binding sites detect cell-bound plasminogen in blood
Authors: Félez Jordi , Jardí Mercè , Fàbregas Pere , Parmer Robert J. , Miles Lindsey A. 
Published: May 2012

AbstractBinding of Glu-plasminogen (the native, circulating form of the zymogen) to cells results in enhancement of its activation. Cell-associated plasmin proteolytic activity is a key component of physiologic and pathologic processes requiring extracellular matrix degradation. Recently, we developed antiplasminogen mAbs that recognize receptor-induced binding sites (RIBS) in Glu-plasminogen and, therefore, preferentially react with cell-associated Glu-plasminogen in the presence of soluble Glu-plasminogen. Here we have used FACS with a representative antiplasminogen receptor-induced binding site mAb, mAb49, to examine whether plasminogen associates with peripheral blood cells in blood. Plasminogen binding to neutrophils, monocytes, B-lymphocytes, T-lymphocytes, and platelets was clearly detected. Treatment of whole blood with lipopolysaccharide or 12-0 tetradecanoylphorbol-13-acetate up-regulated plasminogen binding to neutrophils and in vivo treatment with all-trans retinoic acid decreased plasminogen binding to acute promyelocytic leukemia blasts. Our results demonstrate that mAb49 can be used to monitor cell-bound plasminogen in blood under both normal and pathologic conditions.
Phenytoin versus Leviteracetam for Seizure Prophylaxis after brain injury – a meta analysis
Authors: Zafar Syed Nabeel , Khan Abdul Ahad , Ghauri Asfar Ayaz , Shamim Muhammad Shahzad 
Published: May 2012

Abstract

Background
Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.

Methods
An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures.

Results
The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate’s Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79).

Conclusions
Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.
Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
Authors: Gamarra-Luques Carlos D , Goyeneche Alicia A , Hapon Maria B , Telleria Carlos M 
Published: May 2012

Abstract

Background
Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.

Methods
We established an in vitro approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.

Results
Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.

Conclusions
Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.
Prevalence of chronic musculoskeletal disorders in elderly Brazilians: a systematic review of the literature
Authors: Miranda Vivian S , deCarvalho Vivielle BF , Machado Luciana AC , Dias João Marcos D 
Published: May 2012

Abstract

Background
Population ageing is a worldwide phenomenon that has recently challenged public healthcare systems. The knowledge of the burden of chronic musculoskeletal disorders in elders is still limited, particularly in the developing world. This systematic review aimed to investigate the prevalence of chronic musculoskeletal disorders in elderly Brazilians.

Methods
A comprehensive literature search was performed in five electronic databases (from inception to January 2012) and completed by additional searches in reference lists. Two review authors independently selected the eligible studies and extracted data on participants’ characteristics and rates of chronic musculoskeletal disorders. One review author extracted methodological quality data. We performed a critical synthesis of the results, which were grouped into the diagnoses “chronic musculoskeletal pain” or “specific musculoskeletal diagnoses”.

Results
Twenty five studies reporting on a total of 116,091 elderly Brazilians were included. Eight studies (32%) were of high methodological quality. There was a large variation in the measure of prevalence used by individual studies and in their definition of chronic pain. Prevalence estimates reached 86% for chronic musculoskeletal pain in any location. Studies investigating multiple pain sites found the lower limb and the spine to be the most prevalent complaints (50% each). Arthritis and rheumatism (including osteoarthritis) were the most prevalent specific musculoskeletal diagnoses (9% to 40%), followed by herniated disc (6% to 27%).

Conclusions
Despite the growth of the elderly population worldwide, high-quality research on the burden of chronic musculoskeletal disorders in the elderly is still scarce. Future healthcare research focusing on this age group should be a priority in developing countries since their public healthcare systems are not yet fully prepared to accommodate the needs of an aging population.
Comparative cross-sectional study of empathy among first year and final year medical students in Jimma University, Ethiopia: Steady state of the heart and opening of the eyes
Authors: Dehning Sandra , Girma Eshetu , Gasperi Sarah , Meyer Sebastian , Tesfaye Markos , Siebeck Matthias 
Published: May 2012

Abstract

Background
There is general consent that empathy is crucial for the physician-patient relationship and thus an important issue in medical education. This comparative study was designed to examine the differences in empathy between first year and final year medical students in Jimma University, Ethiopia.

Methods
A comparative cross-sectional study among 131 first year and 106 final year medical students was conducted in Jimma University, Ethiopia on academic year 2010/11. The study subjects were selected using simple random sampling technique from the list of the students. Study participation was voluntary. The Balanced Emotional Empathy Scale (BEES) was used for the detection of “heart-reading”, i.e. emotional empathy and the Reading the Mind in the Eyes test (RME-R test) to evaluate “mind-reading”, i.e. cognitive empathy. We performed t-test to compare the mean difference in empathy and RME-R scores between the two groups of students. A linear regression was computed to identify potential factors influencing the BEES and RME-R.

Results
Out of the total 237 students, 207 (87.3%) were males. The mean age of first year and final year students was 19.3 ± 1.1 and 24.0 ± 1.4 years respectively. First year students have scored 40.6 ± 23.8 while final year students scored 41.5 ± 20.8 mean in the BEES measuring emotional empathy score. However, this difference was not statistically significant (t = −0.30, df = 231, P-value >0.05). Final year students had significantly higher mean cognitive empathy score (17.8 ± 4.5) than first year students (14.4 ± 4.8) [β = 2.7, 95%CI (1.20, 4.13)]. Males had scored lower cognitive [β = −2.5, 95%CI (−4.37, −0.66)] and emotional empathy [β = −12.0, 95%CI (−21.66, −5.46)].

Conclusions
Low emotional (BEES) and cognitive empathy sores were found in first year and final year students of Jimma University could have implications on the medical education curricula. Medical education targeted at enhancing emotional empathy and increasing cognitive empathy is required by segmenting with gender for effective physician-patient interaction. The influence of empathy on clinical competence should be studied using more rigorous design.
The impact of decision aids to enhance shared decision making for diabetes (the DAD study): protocol of a cluster randomized trial
Authors: LeBlanc Annie , Ruud Kari L , Branda Megan E , Tiedje Kristina , Boehmer Kasey R , Pencille Laurie J , Van Houten Holly , Matthews Marc , Shah Nilay D , May Carl R , Yawn Barbara P , Montori Victor M 
Published: May 2012

Abstract

Background
Shared decision making contributes to high quality healthcare by promoting a patient-centered approach. Patient involvement in selecting the components of a diabetes medication program that best match the patient’s values and preferences may also enhance medication adherence and improve outcomes. Decision aids are tools designed to involve patients in shared decision making, but their adoption in practice has been limited. In this study, we propose to obtain a preliminary estimate of the impact of patient decision aids vs. usual care on measures of patient involvement in decision making, diabetes care processes, medication adherence, glycemic and cardiovascular risk factor control, and resource utilization. In addition, we propose to identify, describe, and explain factors that promote or inhibit the routine embedding of decision aids in practice.

Methods/Design
We will be conducting a mixed-methods study comprised of a cluster-randomized, practical, multicentered trial enrolling clinicians and their patients (n = 240) with type 2 diabetes from rural and suburban primary care practices (n = 8), with an embedded qualitative study to examine factors that influence the incorporation of decision aids into routine practice. The intervention will consist of the use of a decision aid (Statin Choice and Aspirin Choice, or Diabetes Medication Choice) during the clinical encounter. The qualitative study will include analysis of video recordings of clinical encounters and in-depth, semi-structured interviews with participating patients, clinicians, and clinic support staff, in both trial arms.

Discussion
Upon completion of this trial, we will have new knowledge about the effectiveness of diabetes decision aids in these practices. We will also better understand the factors that promote or inhibit the successful implementation and normalization of medication choice decision aids in the care of chronic patients in primary care practices.

Trial registration
NCT00388050
β3 integrin modulates transforming growth factor beta induced (TGFBI) function and paclitaxel response in ovarian cancer cells
Authors: Tumbarello David A , Temple Jillian , Brenton James D 
Published: May 2012

Abstract

Background
The extracellular matrix (ECM) has a key role in facilitating the progression of ovarian cancer and we have shown recently that the secreted ECM protein TGFBI modulates the response of ovarian cancer to paclitaxel-induced cell death.

Results
We have determined TGFBI signaling from the extracellular environment is preferential for the cell surface αvβ3 integrin heterodimer, in contrast to periostin, a TGFBI paralogue, which signals primarily via a β1 integrin-mediated pathway. We demonstrate that suppression of β1 integrin expression, in β3 integrin-expressing ovarian cancer cells, increases adhesion to rTGFBI. In addition, Syndecan-1 and −4 expression is dispensable for adhesion to rTGFBI and loss of Syndecan-1 cooperates with the loss of β1 integrin to further enhance adhesion to rTGFBI. The RGD motif present in the carboxy-terminus of TGFBI is necessary, but not sufficient, for SKOV3 cell adhesion and is dispensable for adhesion of ovarian cancer cells lacking β3 integrin expression. In contrast to TGFBI, the carboxy-terminus of periostin, lacking a RGD motif, is unable to support adhesion of ovarian cancer cells. Suppression of β3 integrin in SKOV3 cells increases resistance to paclitaxel-induced cell death while suppression of β1 integrin has no effect. Furthermore, suppression of TGFBI expression stimulates a paclitaxel resistant phenotype while suppression of fibronectin expression, which primarily signals through a β1 integrin-mediated pathway, increases paclitaxel sensitivity.

Conclusions
Therefore, different ECM components use distinct signaling mechanisms in ovarian cancer cells and in particular, TGFBI preferentially interacts through a β3 integrin receptor mediated mechanism to regulate the response of cells to paclitaxel-induced cell death.
Clinical proteomics and OMICS clues useful in translational medicine research
Authors: López Elena , Madero Luis , López-Pascual Juan , Latterich Martin 
Published: May 2012

Abstract
Since the advent of the new proteomics era more than a decade ago, large-scale studies of protein profiling have been used to identify distinctive molecular signatures in a wide array of biological systems, spanning areas of basic biological research, clinical diagnostics, and biomarker discovery directed toward therapeutic applications. Recent advances in protein separation and identification techniques have significantly improved proteomic approaches, leading to enhancement of the depth and breadth of proteome coverage.
Proteomic signatures, specific for multiple diseases, including cancer and pre-invasive lesions, are emerging. This article combines, in a simple manner, relevant proteomic and OMICS clues used in the discovery and development of diagnostic and prognostic biomarkers that are applicable to all clinical fields, thus helping to improve applications of clinical proteomic strategies for translational medicine research.
SITC 26th annual meeting – summary
Authors: Romano Emanuela , Nardelli-Haefliger Denise , Donda Alena , Corgnac Stephanie , Romero Pedro 
Published: May 2012

Abstract
The 26th annual meeting of the Society for Immunotherapy of Cancer took place in Bethesda on November 4 to 6, 2011 and was organized by Charles G. Drake (Johns Hopkins University) Dolores J. Schendel (Helmholtz Zentrum Muenchen – German Research Center for Environmental Health Institute of Molecular Immunology), Jeffrey Schlom (National Cancer Institute, National Institutes of Health), and Jedd D. Wolchok (Memorial Sloan-Kettering Cancer Center). It was an event marked by a number of extraordinary circumstances: it attracted a record attendance of 805 participants from 24 different countries. The gathering came in the wake of great as well as very sad news for the tumor immunology community. Good news included the approval of anti-CTLA-4 as a therapy for metastatic melanoma in April and the announcement in early October of the Nobel Prize in Physiology and Medicine awarded to pioneering studies in the field of immunology. Indeed, one part of the prize went to Dr. Bruce Beutler, Scripps Research Institute, La Jolla, USA and Dr. Jules Hoffman, Institute for Molecular Cell Biology, Strasbourg, France, for their discoveries in innate immunity and the other part to Dr. Ralph Steinman, The Rockfeller University, New York, for his discovery of dendritic cells. Sad news was the losses of two giants in the field. Jürg Tschopp of the University of Lausanne in March and Ralph Steinman, who passed away just three days before his Nobel Prize announcement. The loss of these two charismatic scientific leaders was particularly sad for the Annual Meeting as both J. Tschopp and R. Steinman were confirmed speakers at this meeting: the former to deliver the keynote lecture and the latter as recipient of the Richard V. Smalley prize.
Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011
Authors: Forero Ivan Martinez , Okada Hideho , Topalian Suzanne L , Gajewski Thomas F , Korman Alan J , Melero Ignacio 
Published: May 2012

Abstract
Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and “perceived” business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace.