bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coregulated Genes Link Sulfide:Quinone Oxidoreductase and Arsenic Metabolism in Synechocystis sp. Strain PCC6803
Authors: Nagy Csaba I. , Vass Imre , Rákhely Gábor , Vass István Zoltán , Tóth András , Duzs Ágnes , Peca Loredana , Kruk Jerzy , Kós Péter B. 
Published: July 2014

ABSTRACT

Although the biogeochemistry of the two environmentally hazardous compounds arsenic and sulfide has been extensively investigated, the biological interference of these two toxic but potentially energy-rich compounds has only been hypothesized and indirectly proven. Here we provide direct evidence for the first time that in the photosynthetic model organism
Synechocystis
sp. strain PCC6803 the two metabolic pathways are linked by coregulated genes that are involved in arsenic transport, sulfide oxidation, and probably in sulfide-based alternative photosynthesis. Although
Synechocystis
sp. strain PCC6803 is an obligate photoautotrophic cyanobacterium that grows via oxygenic photosynthesis, we discovered that specific genes are activated in the presence of sulfide or arsenite to exploit the energy potentials of these chemicals. These genes form an operon that we termed
suoRSCT
, located on a transposable element of type IS
4
on the plasmid pSYSM of the cyanobacterium.
suoS
(sll5036) encodes a light-dependent, type I sulfide:quinone oxidoreductase. The
suoR
(sll5035) gene downstream of
suoS
encodes a regulatory protein that belongs to the ArsR-type repressors that are normally involved in arsenic resistance. We found that this repressor has dual specificity, resulting in 200-fold induction of the operon upon either arsenite or sulfide exposure. The
suoT
gene encodes a transmembrane protein similar to chromate transporters but in fact functioning as an arsenite importer at permissive concentrations. We propose that the proteins encoded by the
suoRSCT
operon might have played an important role under anaerobic, reducing conditions on primordial Earth and that the operon was acquired by the cyanobacterium via horizontal gene transfer.
Future Care Planning for patients approaching end-of-life with advanced heart disease: an interview study with patients, carers and healthcare professionals exploring the content, rationale and design of a randomised clinical trial
Authors: Denvir Martin A , Highet Gill , Robertson Shirley , Cudmore Sarah , Reid Janet , Ness Andrea , Hogg Karen , Weir Christopher , Murray Scott , Boyd Kirsty 
Published: July 2014

ObjectiveTo explore the optimal content and design of a clinical trial of an end-of-life intervention for advanced heart disease with patients, carers and healthcare professionals.DesignQualitative interview and focus group study.SettingCommunity and hospital-based focus groups and interviews.ParticipantsStable community-dwelling patients, informal carers (PC, n=15) and primary and secondary care based healthcare professionals (HCP, n=11).ResultsPC highlighted fragmentation of services and difficulty in accessing specialist care as key barriers to good care. They felt that time for discussion with HCP was inadequate within current National Health Service (NHS) healthcare systems. HCP highlighted uncertainty of prognosis, explaining mortality risk to patients and switching from curative to palliative approaches as key challenges. Patient selection, nature of the intervention and relevance of trial outcomes were identified by HCP as key challenges in the design of a clinical trial.ConclusionsPC and HCP expressed a number of concerns relevant to the nature and content of an end-of-life intervention for patients with advanced heart disease. The findings of this study are being used to support a phase II randomised clinical trial of Future Care Planning in advanced heart disease.
Lower levels of high-density lipoprotein cholesterol in urban Africans presenting with communicable versus non-communicable forms of heart disease: the ‘Heart of Soweto’ hospital registry study
Authors: Lyons Jasmine G , Sliwa Karen , Carrington Melinda J , Raal Frederick , Pretorius Sandra , Thienemann Friedrich , Stewart Simon 
Published: July 2014

ObjectivesTo investigate if urban Africans displayed lower levels of atheroprotective high-density lipoprotein cholesterol (HDLC) when presenting with communicable versus non-communicable forms of heart disease (HD) as both acute infection and chronic inflammation reduce HDLC levels.DesignHospital registry of 5328 de novo cases of HD over a 3-year period.SettingCardiology Unit, Baragwanath Hospital in Soweto, South Africa.ParticipantsA total of 1199 patients of African descent (59% women; 57.0±13.4 years) had fasting blood lipid levels (total cholesterol (TC), triglyceride, HDLC and low-density lipoprotein cholesterol (LDLC)) documented on admission. Serum inflammatory marker C reactive protein (CRP) was measured in a subset of 367 patients (31% of cases).Main outcome measuresLipid profiles were compared according to prespecified classification of non-communicable (eg, hypertensive HD) versus communicable (eg, rheumatic HD) HD. Low HDLC was defined as <1.0 mmol/L for men and <1.2 mmol/L for women, according to applicable South African Clinical Guidelines.ResultsOverall 694 (58%) of those presenting with HD had low HDLC levels; 344 of 678 (51%) and 350 of 521 (67%) for non-communicable and communicable, respectively (p<0.001). Comparatively, overall prevalence of high TC was 32% and high LDLC was 37%. On an adjusted basis, those with non-communicable HD were more likely to record a low HDLC relative to non-communicable presentations (odds ratio (OR) 1.91, 95% CI 1.42 to 2.57; p<0.001). There was a strong relationship between low HDLC and higher levels of CRP, but only in women.ConclusionsDespite largely favourable lipid profiles, there are clear differences according to aetiology of underlying HD in urban Africans, with younger patients with communicable HD having particularly low levels of HDLC. Appropriate prospective evidence is needed to determine if persistent low levels of HDLC expose patients to increased, long-term risk of atherosclerotic forms of HD. The women-only inverse association between HDLC and CRP warrants further investigation.
Decreased facial expression variability in patients with serious cardiopulmonary disease in the emergency care setting
Authors: Kline Jeffrey A , Neumann Dawn , Haug Melissa A , Kammer David J , Krabill Virginia A 
Published: July 2014

Background and objectiveThe hypothesis of the present work derives from clinical experience that suggests that patients who are more ill have less facial expression variability in response to emotional cues.MethodsProspective study of diagnostic accuracy from a convenience sample of adult patients with dyspnoea and chest pain in an emergency department. Patients viewed three stimulus slides on a laptop computer that were intended to evoke a change in facial affect. The computer simultaneously video recorded patients’ facial expressions. Videos were examined by two independent blinded observers who analysed patients’ facial expressions using the Facial Action Coding System (FACS). Patients were followed for predefined serious cardiopulmonary diagnosis (Disease+) within 14 days (acute coronary syndrome, pulmonary embolism, pneumonia, aortic or oesophageal disasters or new cancer). The main analysis compared total FACS scores, and action units of smile, surprise and frown between Disease+ and Disease−.ResultsOf 50 patients, 8 (16%) were Disease+. The two observers had 92% exact agreement on the FACS score from the first stimulus slide. During stimulus slide 1, the median of all FACS values from Disease+ patients was 3.4 (1st–3rd quartiles 1–6), significantly less than the median of 7 (3–14) from D−patients (p=0.019, Mann–Whitney U). Expression of surprise had the largest difference between Disease+ and Disease−(area under the receiver operating characteristic curve 0.75, 95% CI 0.52 to 0.87).ConclusionsWith a single visual stimulus, patients with serious cardiopulmonary diseases lacked facial expression variability and surprise affect. Our preliminary findings suggest that stimulus-evoked facial expressions from emergency department patients with cardiopulmonary symptoms might be a useful component of gestalt pretest probability assessment.
USP9X Downregulation Renders Breast Cancer Cells Resistant to Tamoxifen
Authors: Oosterkamp Hendrika M. , Hijmans E. Marielle , Brummelkamp Thijn R. , Canisius Sander , Wessels Lodewyk F.A. , Zwart Wilbert , Bernards René 
Published: July 2014

Abstract
Tamoxifen is one of the most widely used endocrine agents for the treatment of estrogen receptor α (ERα)–positive breast cancer. Although effective in most patients, resistance to tamoxifen is a clinically significant problem and the mechanisms responsible remain elusive. To address this problem, we performed a large scale loss-of-function genetic screen in ZR-75-1 luminal breast cancer cells to identify candidate resistance genes. In this manner, we found that loss of function in the deubiquitinase USP9X prevented proliferation arrest by tamoxifen, but not by the ER downregulator fulvestrant. RNAi-mediated attenuation of USP9X was sufficient to stabilize ERα on chromatin in the presence of tamoxifen, causing a global tamoxifen-driven activation of ERα-responsive genes. Using a gene signature defined by their differential expression after USP9X attenuation in the presence of tamoxifen, we were able to define patients with ERα-positive breast cancer experiencing a poor outcome after adjuvant treatment with tamoxifen. The signature was specific in its lack of correlation with survival in patients with breast cancer who did not receive endocrine therapy. Overall, our findings identify a gene signature as a candidate biomarker of response to tamoxifen in breast cancer. Cancer Res; 74(14); 3810–20. ©2014 AACR.
High Expression of CAI2, a 9p21-Embedded Long Noncoding RNA, Contributes to Advanced-Stage Neuroblastoma
Authors: Barnhill Lisa M. , Williams Richard T. , Cohen Olga , Kim Youngjin , Batova Ayse , Mielke Jenna A. , Messer Karen , Pu Minya , Bao Lei , Yu Alice L. , Diccianni Mitchell B. 
Published: July 2014

Abstract
Neuroblastoma is a pediatric cancer with significant genomic and biologic heterogeneity. p16 and ARF, two important tumor-suppressor genes on chromosome 9p21, are inactivated commonly in most cancers, but paradoxically overexpressed in neuroblastoma. Here, we report that exon γ in p16 is also part of an undescribed long noncoding RNA (lncRNA) that we have termed CAI2 (CDKN2A/ARF Intron 2 lncRNA). CAI2 is a single-exon gene with a poly A signal located in but independent of the p16/ARF exon 3. CAI2 is expressed at very low levels in normal tissue, but is highly expressed in most tumor cell lines with an intact 9p21 locus. Concordant expression of CAI2 with p16 and ARF in normal tissue along with the ability of CAI2 to induce p16 expression suggested that CAI2 may regulate p16 and/or ARF. In neuroblastoma cells transformed by serial passage in vitro, leading to more rapid proliferation, CAI2, p16, and ARF expression all increased dramatically. A similar relationship was also observed in primary neuroblastomas where CAI2 expression was significantly higher in advanced-stage neuroblastoma, independently of MYCN amplification. Consistent with its association with high-risk disease, CAI2 expression was also significantly associated with poor clinical outcomes, although this effect was reduced when adjusted for MYCN amplification. Taken together, our findings suggested that CAI2 contributes to the paradoxical overexpression of p16 in neuroblastoma, where CAI2 may offer a useful biomarker of high-risk disease. Cancer Res; 74(14); 3753–63. ©2014 AACR.
Phase I Study of RGB-286638, A Novel, Multitargeted Cyclin-Dependent Kinase Inhibitor in Patients with Solid Tumors
Authors: van der Biessen Diane A.J. , Burger Herman , de Bruijn Peter , Lamers Cor H.J. , Naus Nicole , Loferer Hannes , Wiemer Erik A.C. , Mathijssen Ron H.J. , de Jonge Maja J.A. 
Published: July 2014

Abstract
Purpose: RGB-286638 is a multitargeted inhibitor with targets comprising the family of cyclin-dependent kinases (CDK) and a range of other cancer-relevant tyrosine and serine/threonine kinases. The objectives of this first in human trial of RGB-286638, given i.v. on days 1 to 5 every 28 days, were to determine the maximum tolerated dose (MTD) and to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of this new drug.
Experimental Design: Sequential cohorts of 3 to 6 patients were treated per dose level. Blood, urine samples, and skin biopsies for full PK and/or PD analyses were collected.
Results: Twenty-six patients were enrolled in 6-dose levels from 10 to 160 mg/d. Four dose-limiting toxicities were observed in 2 of the 6 patients enrolled at the highest dose level. These toxicities were AST/ALT elevations in 1 patient, paroxysmal supraventricular tachycardias (SVTs), hypotension, and an increase in troponin T in another patient. The plasma PK of RGB-286638 was shown to be linear over the studied doses. The interpatient variability in clearance was moderate (variation coefficient 7%–36%). The PD analyses in peripheral blood mononuclear cells, serum (apoptosis induction) and skin biopsies (Rb, p-Rb, Ki-67, and p27KIP1 expression) did not demonstrate a consistent modulation of mechanism-related biomarkers with the exception of lowered Ki-67 levels at the MTD level. The recommended MTD for phase II studies is 120 mg/d.
Conclusions: RGB-286638 is tolerated when administered at 120 mg/d for 5 days every 28 days. Prolonged disease stabilization (range, 2–14 months) was seen across different dose levels. Clin Cancer Res; 20(18); 4776–83. ©2014 AACR.
Use of Aspirin for Primary and Secondary Cardiovascular Disease Prevention in the United States, 2011–2012
Authors: Mainous Arch G. , Tanner Rebecca J. , Shorr Ronald I. , Limacher Marian C. 
Published: July 2014

Background

Aspirin use has been shown to be an effective tool in cardiovascular disease (
CVD
) prevention among high‐risk patients. The patient‐reported physician recommendation for aspirin as preventive therapy among high‐ and low‐risk patients is unknown.

Methods and Results

We conducted an analysis of the National Health and Nutrition Examination Survey 2011–2012 to examine the use of aspirin for
CVD
prevention. Patients without previously diagnosed
CVD
were classified into high and low risk based on their Framingham Risk Score (10‐year coronary heart disease risk). Among patients without previously diagnosed
CVD
, 22.5% were classified as high risk. Of the high‐risk individuals, 40.9% reported being told by their physician to take aspirin, with 79.0% complying. Among those who were at low risk, 26.0% were told by their physician to take aspirin, with 76.5% complying. Logistic regression analysis indicated that age, access to a regular source of care, education, and insurance status were significant predictors of patient‐reported physician recommendations for aspirin use for primary prevention. Among high‐risk patients, age, race, and insurance status were significant predictors of reported recommendations for aspirin use. Among low‐risk patients, age, education, obesity, and insurance status were significant predictors of reported recommendations for aspirin use.

Conclusions
Patient reports indicate nonideal rates of being told to take aspirin, for both high‐ and low‐risk patients for primary prevention. Clinical decision support tools that could assist physicians in identifying patients at risk may increase patient reports of physician recommendations for aspirin use.
Understanding Midlatitude Jet Variability and Change Using Rossby Wave Chromatography: Methodology
Authors: Lorenz David J. 
Published: July 2014

Abstract
Rossby wave chromatography (RWC) is implemented in a linearized barotropic model as a tool to diagnose and understand the interaction between the midlatitude jet and the eddies. Given the background zonal-mean flow and the space–time structure of the baroclinic wave activity source, RWC calculates the space–time structure of the upper-tropospheric eddy momentum fluxes. Using the convergence of the vertical Eliassen–Palm (E–P) flux in the upper troposphere as the wave source, RWC reproduces the main features of a GCM’s mean state and response to external forcing. When coupled to the zonal-mean zonal wind and a simple model of wave activity source phase speed changes, RWC also simulates the temporal evolution of the GCM’s internally generated zonal-mean zonal wind anomalies. Because the full space–time structure of the baroclinic wave activity source is decoupled from the background flow, RWC can be used to isolate and quantify the dynamical mechanisms responsible for 1) the poleward shift of the midlatitude jet and 2) the feedbacks between the eddy momentum fluxes and the background flow in general.
Hemispheric asymmetry measured by texture analysis and diffusion tensor imaging in two multiple sclerosis subtypes
Authors: Savio Sami , Hakulinen Ullamari , Ryymin Pertti , Hagman Sanna , Dastidar Prasun , Soimakallio Seppo , Elovaara Irina , Eskola Hannu 
Published: July 2014

Background This paper addresses two subtypes of multiple sclerosis (MS), primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS). The separation of PPMS and RRMS is challenging in certain cases. Purpose To quantitatively determine MS subtypes using texture analysis (TA) and diffusion tensor imaging (DTI). Material and Methods T1-weighted (T1W) magnetic resonance imaging (MRI) and DTI of the left and right brain hemispheres of 17 patients with PPMS and 19 patients with RRMS were studied. Areas of the caudate nucleus and thalamus were investigated as normal appearing gray matter (NAGM), and areas of the cerebral peduncle and centrum semiovale were investigated as normal appearing white matter (NAWM). The described locations were symmetrical and were accurately marked. TA was performed on the T1W images, and the fractional anisotropy and apparent diffusion coefficient were determined from the DTI data. Results Hemispherical differences were found with both TA and DTI. Several texture and diffusion tensor parameter values calculated for the left and right hemispheres of the patients showed statistically significant differences. The patients with RRMS had greater significant differences ( P < 0.01) in the thalamus between the hemispheres than did the patients with PPMS. The TA classification accuracy of the PPMS and RRMS subtypes was above 80%. Conclusion TA can be helpful when distinguishing between PPMS and RRMS, while DTI appears to reveal the hemispherical asymmetry of RRMS patients.
Biomechanical Comparison of Arthroscopic Single- and Double-Row Repair Techniques for Acute Bony Bankart Lesions
Authors: Spiegl Ulrich J. , Smith Sean D. , Todd Jocelyn N. , Coatney Garrett A. , Wijdicks Coen A. , Millett Peter J. 
Published: July 2014

Background: Single- and double-row arthroscopic reconstruction techniques for acute bony Bankart lesions have been described in the literature. Hypothesis: The double-row fixation technique would provide superior reduction and stability of a simulated bony Bankart lesion at time zero in a cadaveric model compared with the single-row technique. Study Design: Controlled laboratory study. Methods: Testing was performed on 14 matched pairs of glenoids with simulated bony Bankart fractures with a defect width of 25% of the glenoid diameter. Half of the fractures were repaired with a double-row technique, while the contralateral glenoids were repaired with a single-row technique. The quality of fracture reduction was measured with a coordinate measuring machine. To determine the biomechanical stability of the repairs, specimens were preconditioned with 10 sinusoidal cycles between 5 and 25 N at 0.1 Hz and then pulled to failure in the anteromedial direction at a rate of 5 mm/min. Loads at 1 mm and 2 mm of fracture displacement were determined. Results: The double-row technique required significantly higher forces to achieve fracture displacements of 1 mm (mean, 60.6 N; range, 39.0-93.3 N; P = .001) and 2 mm (mean, 94.4 N; range, 43.4-151.2 N; P = .004) than the single-row technique (1 mm: mean, 30.2 N; range, 14.0-54.1 N and 2 mm: mean, 63.7 N; range, 26.6-118.8 N). Significantly reduced fracture displacement was seen after double-row repair for both the unloaded condition (mean, 1.1 mm; range, 0.3-2.4 mm; P = .005) and in response to a 10-N anterior force applied to the defect (mean, 1.6 mm; range, 0.5-2.7 mm; P = .001) compared with single-row repair (unloaded: mean, 2.1 mm; range, 1.3-3.4 mm and loaded: mean, 3.4 mm; range, 1.9-4.7 mm). Conclusion: The double-row fixation technique resulted in improved fracture reduction and superior stability at time zero in this cadaveric model. Clinical Relevance: This information may influence the surgical technique used to treat large osseous Bankart fractures and the postoperative rehabilitation protocols implemented when such repair techniques are used.
Nimesulide-Induced Acute Hepatitis
Authors: Sbeit Wisam , Krivoy Norberto , Shiller Moshe , Farah Raymond , Cohen Hector I , Struminger Lili , Reshef Ron 
Published: July 2014

OBJECTIVE: To report the occurrence of nimesulide-induced acute hepatitis confirmed by biopsy and an in vitro lymphocyte toxicity assay. CASE SUMMARY: A 54-year-old Arabic woman treated with nimesulide for chronic low back pain was admitted to the hospital with acute hepatitis confirmed by biopsy. Her liver function test results returned to normal within one month after nimesulide discontinuation. An in vitro lymphocyte toxicity assay confirmed that the liver injury was due to nimesulide exposure. DISCUSSION: A case of acute hepatitis secondary to nimesulide, confirmed by biopsy and a laboratory in vitro assay, is described. Although the occurrence of clinically significant liver damage due to nonsteroidal antiinflammatory drugs (NSAIDs) is low, the enormous consumption of these drugs has made them an important cause of liver damage. Nimesulide, a relatively new NSAID commonly used in Europe, with a relative selectivity to cyclooxygenase type 2, can cause a wide range of liver injuries, from mild abnormal liver function to severe liver injuries. These effects are usually reversible on discontinuation of the drug, but occasionally can progress to fatal hepatic failure. CONCLUSIONS: Drug-induced acute hepatitis is a well-recognized adverse effect of many drugs, including nimesulide. Identification of a drug as a cause for this life-threatening disease is important because the discontinuation of it may be life saving. This article confirms the occurrence of nimesulide-induced hepatitis. It also highlights the importance of monitoring liver function test results after initiating therapy with such a drug.
Oral Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma
Authors: Wong Siu-Fun 
Published: July 2014

OBJECTIVE: To review the preclinical and clinical information related to oral bexarotene approved by the Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. DATA SOURCES: Literature accessed through MEDLINE (from 1990 to July 2000) and provided by the manufacturer. Key search terms included bexarotene, Targretin, LGD1069, and cutaneous T-cell lymphoma. DATA SYNTHESIS: The management of CTCL remains controversial due to its rarity in the US and its heterogeneity. An evaluation focusing on the pharmacology of bexarotene and its role in the management of the different stages of CTCL was conducted. CONCLUSIONS: Bexarotene has demonstrated activity in the treatment of CTCL. The oral route of administration and the adverse effect profile of bexarotene appear to make this drug a favorable option for the treatment of CTCL compared with other systemic therapies. Phase III randomized studies are needed to determine the clinical benefits of bexarotene as monotherapy or combination therapy in the treatment of CTCL.