bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteins Needed to Activate a Transcriptional Response to the Reactive Oxygen Species Singlet Oxygen
Authors: Nam Tae-Wook , Ziegelhoffer Eva C. , Lemke Rachelle A. S. , Donohue Timothy J. 
Published: January 2013

ABSTRACT

Singlet oxygen (
1
O
2
) is a reactive oxygen species generated by energy transfer from one or more excited donors to molecular oxygen. Many biomolecules are prone to oxidation by
1
O
2
, and cells have evolved systems to protect themselves from damage caused by this compound. One way that the photosynthetic bacterium
Rhodobacter sphaeroides
protects itself from
1
O
2
is by inducing a transcriptional response controlled by ChrR, an anti-σ factor which releases an alternative sigma factor, σ
E
, in the presence of
1
O
2
. Here we report that induction of σ
E
-dependent gene transcription is decreased in the presence of
1
O
2
when two conserved genes in the σ
E
regulon are deleted, including one encoding a cyclopropane fatty acid synthase homologue (RSP2144) or one encoding a protein of unknown function (RSP1091). Thus, we conclude that RSP2144 and RSP1091 are each necessary to increase σ
E
activity in the presence of
1
O
2
. In addition, we found that unlike in wild-type cells, where ChrR is rapidly degraded when
1
O
2
is generated, turnover of this anti-σ factor is slowed when cells lacking RSP2144, RSP1091, or both of these proteins are exposed to
1
O
2
. Further, we demonstrate that the organic hydroperoxide
tert
-butyl hydroperoxide promotes ChrR turnover in both wild-type cells and mutants lacking RSP2144 or RSP1091, suggesting differences in the ways different types of oxidants increase σ
E
activity.

IMPORTANCE
Oxygen serves many crucial functions on Earth; it is produced during photosynthesis and needed for other pathways. While oxygen is relatively inert, it can be converted to reactive oxygen species (ROS) that destroy biomolecules, cause disease, or kill cells. When energy is transferred to oxygen, the ROS singlet oxygen is generated. To understand how singlet oxygen impacts cells, we study the stress response to this ROS in
Rhodobacter sphaeroides
, a bacterium that, like plants, generates this compound as a consequence of photosynthesis. This paper identifies proteins that activate a stress response to singlet oxygen and shows that they act in a specific response to this ROS. The identified proteins are found in many free-living, symbiotic, or pathogenic bacteria that can encounter singlet oxygen in nature. Thus, our findings provide new information about a stress response to a ROS of broad biological, agricultural, and biomedical importance.
Delirium in an adult acute hospital population: predictors, prevalence and detection
Authors: Ryan Daniel James , O'Regan Niamh Annmarie , Caoimh Ronán Ó , Clare Josie , O'Connor Marie , Leonard Maeve , McFarland John , Tighe Sheila , O'Sullivan Kathleen , Trzepacz Paula T , Meagher David , Timmons Suzanne 
Published: January 2013

BackgroundTo date, delirium prevalence and incidence in acute hospitals has been estimated from pooled findings of studies performed in distinct patient populations.ObjectiveTo determine delirium prevalence across an acute care facility.DesignA point prevalence study.SettingA large tertiary care, teaching hospital.Patients311 general hospital adult inpatients were assessed over a single day. Of those, 280 had full data collected within the study's time frame (90%).MeasurementsInitial screening for inattention was performed using the spatial span forwards and months backwards tests by junior medical staff, followed by two independent formal delirium assessments: first the Confusion Assessment Method (CAM) by trained geriatric medicine consultants and registrars, and, subsequently, the Delirium Rating Scale-Revised-98 (DRS-R98) by experienced psychiatrists. The diagnosis of delirium was ultimately made using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria.ResultsUsing DSM-IV criteria, 55 of 280 patients (19.6%) had delirium versus 17.6% using the CAM. Using the DRS-R98 total score for independent diagnosis, 20.7% had full delirium, and 8.6% had subsyndromal delirium. Prevalence was higher in older patients (4.7% if <50 years and 34.8% if >80 years) and particularly in those with prior dementia (OR=15.33, p<0.001), even when adjusted for potential confounders. Although 50.9% of delirious patients had pre-existing dementia, it was poorly documented in the medical notes. Delirium symptoms detected by medical notes, nurse interview and patient reports did not overlap much, with inattention noted by professional staff, and acute change and sleep-wake disturbance noted by patients.ConclusionsOur point prevalence study confirms that delirium occurs in about 1/5 of general hospital inpatients and particularly in those with prior cognitive impairment. Recognition strategies may need to be tailored to the symptoms most noticed by the detector (patient, nurse or primary physician) if formal assessments are not available.
Can the London 2012 Olympics ‘inspire a generation’ to do more physical or sporting activities? An overview of systematic reviews
Authors: Mahtani Kamal Ram , Protheroe Joanne , Slight Sarah Patricia , Demarzo Marcelo Marcos Piva , Blakeman Thomas , Barton Christopher A , Brijnath Bianca , Roberts Nia 
Published: January 2013

ObjectiveTo examine if there is an increased participation in physical or sporting activities following an Olympic or Paralympic games.DesignOverview of systematic reviews.MethodsWe searched the Medline, Embase, Cochrane, DARE, SportDISCUS and Web of Knowledge databases. In addition, we searched for ‘grey literature’ in Google, Google scholar and on the International Olympic Committee websites. We restricted our search to those reviews published in English. We used the AMSTAR tool to assess the methodological quality of those systematic reviews included.Primary and secondary outcome measuresThe primary outcome was evidence for an increased participation in physical or sporting activities. Secondary outcomes included public perceptions of sport during and after an Olympic games, barriers to increased sports participation and any other non-sporting health benefits.ResultsOur systematic search revealed 844 citations, of which only two matched our inclusion criteria. The quality of these two reviews was assessed by three independent reviewers as ‘good’ using the AMSTAR tool for quality appraisal. Both reviews reported little evidence of an increased uptake of sporting activity following an Olympic Games event. Other effects on health, for example, changes in hospital admissions, suicide rates and drug use, were cited although there was insufficient evidence to see an overall effect.ConclusionThere is a paucity of evidence to support the notion that hosting an Olympic games leads to an increased participation in physical or sporting activities for host countries. We also found little evidence to suggest other health benefits. We conclude that the true success of these and future games should be evaluated by high-quality, evidence-based studies that have been commissioned before, during and following the completion of the event. Only then can the true success and legacy of the games be established.
Left ventricular assist device withdrawal: an ethical discussion
Authors: McLean Sarah , Dhonnchu Tara Ni , Mahon Niall , McQuillan Regina , Gordijn Bert , Ryan Karen 
Published: January 2013

Specialist palliative care (SPC) services are increasingly integrated with chronic heart failure (CHF) services. Left ventricular assist devices (LVADs) represent an advance in the management of advanced CHF, but may pose ethical challenges for SPC services providing care to this population.The patient received an LVAD as ‘bridge-to-heart-transplant,’ but subsequently experienced multiple cerebral haemorrhages, resulting in neurological deficits, and severe functional impairment. The risk of further cerebral events precluded ongoing anticoagulation, and she was transferred to an SPC inpatient unit for symptom control and end-of-life care. Following discussion within the multi-disciplinary team and with the patient's family, LVAD support was withdrawn, and the patient died peacefully. This piece reviews the ethical considerations that informed decision-making, in particular, autonomy, informed consent and futility. In addition, the question of the nature of LVADs is debated and how the perceptions of the patient, and others, of the device may influence decision-making around withdrawal of treatment.
The SPEED study: initial clinical evaluation of the Penumbra novel 054 Reperfusion Catheter
Authors: Frei Don , Gerber Johannes , Turk Aquilla , McPherson Malia , Heck Don , Hui Ferdinand , Joseph Gregory , Jahan Reza , Miskolczi Laszlo , Carpenter Jeffrey , Grobelny Thomas , Goddard Jim , Turner Raymond D , Huddle Dan , Bellon Richard , Chaudry Imran 
Published: January 2013

Background and purposeRevascularization of acute ischemic stroke from a large vessel occlusion continues to be a challenge with current thrombectomy devices. The purpose of the SPEED study was to report the safety and effectiveness of the Penumbra 054 Reperfusion Catheter System in revascularizing large vessel occlusions.MethodsIn this retrospective multicenter study, data were collected from patients with angiographic evidence of large vessel occlusion treated with the Penumbra 054 device as the intended primary therapy. Clinical outcome data were collected with 90-day follow-up and the results were compared with those from the Penumbra Pivotal trial.ResultsEighty-seven target vessels in 86 consecutive patients treated with the Penumbra 054 device were included. The Thrombolysis In Myocardial Infarction (TIMI) 2 or 3 revascularization rate was 91% compared with a reported 82% in the Penumbra Pivotal trial. This was accomplished in a median time of 20 min compared with 45 min in the Penumbra Pivotal trial (p<0.0001). Eighteen (21%) patients experienced an intracranial hemorrhage of which 12 (14%) were symptomatic. Good neurologic outcome (modified Rankin scores ≤ 2) at 90-day follow-up was achieved in 34.9% of patients compared with 25% reported in the Penumbra Pivotal trial. All-cause mortality was 25.6%.ConclusionsThese results suggest that the Penumbra 054 is a fast, safe and effective revascularization tool for patients experiencing ischemic stroke secondary to large vessel occlusive disease. Improvements in speed and effectiveness of revascularization probably contributed to improved outcomes.
A Conversation with Paul Greengard
Authors: Greengard Paul , Nestler Eric J. 
Published: January 2013

Introduction Paul Greengard was born in New York City in 1925. After completing high school, he served three years in the US Navy during World War II and then completed his bachelor's degree at Hamilton College where he majored in physics and mathematics. He obtained a PhD in biophysics from Johns Hopkins University in 1953 and pursued postdoctoral training with Wilhelm Feldberg at the National Institute for Medical Research in England. After eight years as head of biochemistry at Geigy, and sabbaticals at Albert Einstein College of Medicine and Vanderbilt University, he joined the Yale University faculty as a full professor of pharmacology in 1968. While he was at Yale, Greengard's laboratory performed groundbreaking research, which demonstrated a role for cyclic nucleotides, protein kinases and protein phosphatases, and their protein substrates in the regulation of synaptic transmission. In 1983, Greengard moved to The Rockefeller University, where he has since served as the Vincent Astor Professor and Head of the Laboratory of Molecular and Cellular Neuroscience. Greengard's paradigm-shifting research has continued at Rockefeller and has informed our understanding and possible treatment of a host of brain disorders, including schizophrenia, Alzheimer's disease, Parkinson's disease, and depression. He is the author of more than 950 research articles and reviews. Greengard has received numerous awards and honors, including the Nobel Prize in Physiology or Medicine in 2000, the Metropolitan Life Foundation Award for Medical Research, The National Academy of Sciences Award in Neuroscience, the Ralph W. Gerard Prize in Neuroscience for the Society for Neuroscience, and the Karolinska Institutet's Bicentennial Gold Medal. He is a member of the US National Academy of Sciences and the Institute of Medicine of the National Academies. The following interview was conducted on May 29, 2012.
Global DNA Hypomethylation in Peripheral Blood Mononuclear Cells as a Biomarker of Cancer Risk
Authors: Friso Simonetta , Udali Silvia , Guarini Patrizia , Pellegrini Camilla , Pattini Patrizia , Moruzzi Sara , Girelli Domenico , Pizzolo Francesca , Martinelli Nicola , Corrocher Roberto , Olivieri Oliviero , Choi Sang-Woon 
Published: January 2013

Abstract
Background: Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells (PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established.
Methods: From an original sample-set of 753 male and female adults (ages 64.8 ± 7.3 years), PBMCs DNA methylation was measured in 68 subjects with history of cancer at time of enrollment and 62 who developed cancer during follow-up. Age- and sex-matched controls for prevalent and incident cancer cases (n = 68 and 58, respectively) were also selected. Global DNA methylation was assessed by liquid chromatography/mass spectrometry (LC/MS). Methylenetetrahydrofolate reductase (MTHFR) 677C&gt;T genotype and plasma folate concentrations were also determined for the known gene-nutrient interaction affecting DNA methylation.
Results: Cancer subjects had significantly lower PBMCs-DNA methylation than controls [4.39 (95% confidence intervals (CI), 4.25–4.53) vs. 5.13 (95% CI, 5.03–5.21) %mCyt/(mCyt+Cyt); P &lt; 0.0001]. A DNA methylation threshold of 4.74% clearly categorized patients with cancer from controls so that those with DNA methylation less than 4.74% showed an increased prevalence of cancer than those with higher levels (91.5% vs. 19%; P &lt; 0.001). Subjects with cancer at follow-up had, already at enrollment, reduced DNA methylation as compared with controls [4.34 (95% CI, 4.24–4.51) vs. 5.08 (95% CI, 5.05–5.22) %mCyt/(mCyt+Cyt); P &lt; 0.0001]. Moreover, MTHFR677C&gt;T genotype and folate interact for determining DNA methylation, so that MTHFR677TT carriers with low folate had the lowest DNA methylation and concordantly showed a higher prevalence of cancer history (OR, 7.04; 95% CI, 1.52–32.63; P = 0.013).
Conclusions: Genomic PBMCs-DNA methylation may be a useful epigenetic biomarker for early detection and cancer risk estimation.
Impact: This study identifies a threshold for PBMCs-DNA methylation to detect cancer-affected from cancer-free subjects and an at-risk condition for cancer based on genomic DNA methylation and MTHFR677C&gt;T-folate status. Cancer Epidemiol Biomarkers Prev; 22(3); 348–55. ©2012 AACR.
Health Behaviors Predict Higher Interleukin-6 Levels among Patients Newly Diagnosed with Head and Neck Squamous Cell Carcinoma
Authors: Duffy Sonia A. , Teknos Theodoros , Taylor Jeremy M.G. , Fowler Karen E. , Islam Mozaffarul , Wolf Gregory T. , McLean Scott , Ghanem Tamer A. , Terrell Jeffrey E. 
Published: January 2013

Abstract
Background: Health behaviors have been shown to be associated with recurrence risk and survival rates in patients with cancer and are also associated with interleukin-6 (IL-6) levels, but few epidemiologic studies have investigated the relationship of health behaviors and IL-6 among cancer populations. The purpose of the study is to look at the relationship between five health behaviors, viz.: smoking, alcohol problems, body mass index (BMI; a marker of nutritional status), physical activity, and sleep and pretreatment IL-6 levels in persons with head and neck cancer.
Methods: Patients (N = 409) were recruited in otolaryngology clinic waiting rooms and invited to complete written surveys. A medical record audit was also conducted. Descriptive statistics and multivariate analyses were conducted to determine which health behaviors were associated with higher IL-6 levels controlling for demographic and clinical variables among patients with newly diagnosed head and neck cancer.
Results: While smoking, alcohol problems, BMI, physical activity, and sleep were associated with IL-6 levels in bivariate analysis, only smoking (current and former) and decreased sleep were independent predictors of higher IL-6 levels in multivariate regression analysis. Covariates associated with higher IL-6 levels were age and higher tumor stage, whereas comorbidities were marginally significant.
Conclusion: Health behaviors, particularly smoking and sleep disturbances, are associated with higher IL-6 levels among patients with head and neck cancer.
Impact: Treating health behavior problems, especially smoking and sleep disturbances, may be beneficial to decreasing IL-6 levels, which could have a beneficial effect on overall cancer treatment outcomes. Cancer Epidemiol Biomarkers Prev; 22(3); 374–81. ©2012 AACR.
Serum Amyloid A Is Associated with Obesity and Estrogen Receptor–Negative Tumors in Postmenopausal Women with Breast Cancer
Authors: Santana Aline Barros , Gurgel Maria Salete Costa , de Oliveira Montanari Joelma Ferreira , Bonini Flavia Muraro , de Barros-Mazon Silvia 
Published: January 2013

Abstract
Serum amyloid A (SAA) is an acute-phase protein and also an adipokine, which has been associated with the development and prognosis of breast cancer. In the present study, we investigated the association between obesity and SAA in postmenopausal women with breast cancer and its relationship with clinicopathologic characteristics of tumors. Patients were grouped as nonobese or overweight/obese based on body mass index (BMI) plus waist circumference measurement. Serum SAA concentrations were determined by high-sensitivity micro-latex agglutination tests, detected by nephelometry. Serum SAA concentrations were higher in overweight/obese (P = 0.008) patients and this condition was dependent on obesity (BMI and waist circumference), as further shown by multivariate linear regression analysis done for SAA (P = 0.01). Concentrations of SAA were also higher in patients with estrogen receptor–negative (ER−) tumors than in those with estrogen receptor–positive (ER+; P = 0.033). Our results suggest a possible role for SAA in the development and prognosis of obesity-related breast cancer. A follow-up study of this population to assess overall and disease-free survival is in course and should bring contribution to evaluate the clinical role of SAA in breast cancer in the context of obesity. Cancer Epidemiol Biomarkers Prev; 22(2); 270–4. ©2013 AACR.
From Differences in Means between Cases and Controls to Risk Stratification: A Business Plan for Biomarker Development
Authors: Wentzensen Nicolas , Wacholder Sholom 
Published: January 2013

AbstractResearchers developing biomarkers for early detection can determine the potential for clinical benefit at early stages of development. We provide the theoretical background showing the quantitative connection between biomarker levels in cases and controls and clinically meaningful risk measures, as well as a spreadsheet for researchers to use in their own research. We provide researchers with tools to decide whether a test is useful, whether it needs technical improvement, whether it may work only in specific populations, or whether any further development is futile. The methods described here apply to any method that aims to estimate risk of disease based on biomarkers, clinical tests, genetics, environment, or behavior.Significance: Many efforts go into futile biomarker development and premature clinical testing. In many instances, predictions for translational success or failure can be made early, simply based on critical analysis of case–control data. Our article presents well-established theory in a form that can be appreciated by biomarker researchers. Furthermore, we provide an interactive spreadsheet that links biomarker performance with specific disease characteristics to evaluate the promise of biomarker candidates at an early stage. Cancer Discov; 3(2); 148–57. ©2012 AACR.
Prophylaxis Against Venous Thromboembolism in Hospitalized Medically Ill Patients
Authors: Pendergraft Trudy , Liu Xianchen , Edelsberg John , Phatak Hemant , Vera-Llonch Montserrat , Liu Larry Z. , Oster Gerry 
Published: January 2013

Background—
Many hospitalized medically ill patients are at risk of venous thromboembolism (VTE). Risk factors include prior VTE, older age, immobility, obesity, cardiac or respiratory failure, and cancer (at-risk patients). Although guidelines recommend use of VTE prophylaxis for at-risk patients, many may not receive it.

Methods and Results—
Using a database linking admission records from >150 US hospitals to health insurance claims, we identified people ≥40 years of age, hospitalized from 2003 to 2008. We excluded patients who: (1) were treated for VTE or hospitalized in the previous 30 days; (2) were admitted for traumatic injury or surgery; (3) had hypercoagulability at admission; or (4) received therapeutic dosages of low-molecular weight heparin, unfractionated heparin, or fondaparinux at admission. We examined the use of VTE prophylaxis (both pharmacological and nonpharmacological) on day 1 or 2 in hospital among at-risk patients; predictors of receipt of prophylaxis were examined using multivariate logistic regression. The study population consisted of 49 948 patients, of whom 34 374 (69%) were at risk. Only 18% of at-risk patients received VTE prophylaxis on day 1 or 2 in hospital, typically with low-molecular weight heparin (56% of patients receiving prophylaxis), intermittent pneumatic compression (25%), warfarin (16%), or graduated compression stockings (11%). Use of prophylaxis exceeded 25% only in patients admitted from nursing homes and those with prior VTE. Although there were several significant predictors of receipt of VTE prophylaxis, model discrimination was relatively poor (C-statistic=0.61).

Conclusion—
The majority of at-risk hospitalized medically ill patients do not receive VTE prophylaxis.
Prediction of Cardiovascular Events and All-Cause Mortality With Erectile Dysfunction
Authors: Vlachopoulos Charalambos V. , Terentes-Printzios Dimitrios G. , Ioakeimidis Nikolaos K. , Aznaouridis Konstantinos A. , Stefanadis Christodoulos I. 
Published: January 2013

Background—
Erectile dysfunction (ED) carries an independent risk for cardiovascular (CV) events. We conducted a meta-analysis of all longitudinal studies for determining the ability of ED to predict risk of clinical events and to dissect factors influencing this ability.

Methods and Results—

We conducted a comprehensive search of electronic databases through July 2012. Longitudinal studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) were included. Of the 14 studies included (92 757 participants; mean follow-up, 6.1 years; 16 articles), 13 (14 articles) reported results on total CV events (91 831 individuals), 4 on CV mortality (34 761 individuals), 4 on myocardial infarction (35 523 individuals), 6 on cerebrovascular events (27 689 individuals), and 5 on all-cause mortality (17 869 individuals). The pooled RRs for the above-mentioned end points were 1.44 (95% CI, 1.27–1.63), 1.19 (95% CI, 0.97–1.46), 1.62 (95% CI, 1.34–1.96), 1.39 (95% CI, 1.23–1.57), and 1.25 (95% CI, 1.12–1.39), respectively, for men with versus without ED. The RR was higher in intermediate- compared with high- or low-CV-risk populations and with younger age. The RR for studies that diagnosed ED with the use of a questionnaire compared with a single question was higher (RR, 1.61; 95% CI, 1.38–1.86 versus RR, 1.27; 95% CI, 1.18–1.37, respectively;
P
=0.006).

Conclusions—
ED is associated with increased risk of CV events and all-cause mortality. RR is higher at younger ages, in intermediate-risk groups, and when a questionnaire is used instead of a single question.