bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual well-being in cancer and palliative care: an assessment of healthcare professionals’ current practice and training needs
Authors: Gleeson Aoife , Hazell Emily 
Published: March 2017

Sexual well-being is often significantly affected by cancer and its treatments. Previous research shows that a patient's sexual well-being is often overlooked in clinical practice.ObjectivesThe aims of this study were twofold. First, to determine the current practice of healthcare professionals (HCPs) working with cancer and palliative care patients in primary and secondary care settings in relation to sexual well-being. Second, to determine the education requirements of HCPs regarding the management of sexual well-being concerns of cancer/palliative care patients.MethodsAn anonymous electronic questionnaire was sent to assess current practice and education needs relating to the management of sexual well-being in cancer and palliative care.ResultsThe majority of HCPs did not routinely assess sexual well-being in cancer and palliative care patients, with only 13.8% of secondary care staff, 7.9% of district nurses and 4% of general practitioners (GPs) routinely assessing it. The most frequent reason for non-assessment was that it was not the presenting symptom. The majority of respondents felt further support and training would be of benefit, including knowledge of specialist services patients could be referred to, written information for patients and access to assessment tools.ConclusionsThis survey identified that sexual well-being in cancer and palliative care patients is not routinely assessed with the majority of respondents stating that further support and training would be beneficial. The results of this questionnaire will be used to inform and develop sexual well-being training for HCPs working with cancer and palliative care patients.
Two-year outcome after early or late Intervention in non-ST elevation acute coronary syndrome
Authors: Badings Erik A , Remkes Wouter S , The Salem H K , Dambrink Jan-Henk E , Tjeerdsma Geert , Rasoul Saman , Timmer Jorik R , van der Wielen Marloes L J , Lok Dirk J A , Hermanides Renicus S , Van Wijngaarden Jan , Suryapranata Harry , van ’t Hof Arnoud W J 
Published: March 2017

ObjectiveTo compare long-term outcome of an early to a delayed invasive strategy in high-risk patients with non-ST elevation acute coronary syndrome (NSTE-ACS).MethodsThis prospective, multicentre trial included patients with NSTE-ACS and at least two out of three of the following high-risk criteria: (1) evidence of extensive myocardial ischaemia on ECG, (2) elevated biomarkers for myocardial necrosis and (3) age above 65 years. Patients were randomised to either an early (angiography and revascularisation if appropriate <12 hours) or a delayed invasive strategy (>48 hours after randomisation). Endpoint for this prespecified long-term follow-up was the composite incidence of death or reinfarction after 2 years. Data collection was performed by telephone contact with the patients, their relatives or general practitioner and by review of hospital records.ResultsEndpoint status after 2-year follow-up was collected in 521 of 542 initially enrolled patients. Incidence of death or reinfarction was 11.8% in the early and 13.1% in the delayed treatment group (relative risk (RR)=0.90, 95% CI 0.57 to 1.42). No significant differences were found in occurrence of the individual components of the primary endpoint: death 6.1% vs 8.9%, RR 0.69 (95% CI 0.37 to 1.27), reinfarction 6.5% vs 5.4%, RR 1.20 (95% CI 0.60 to 2.38). Post-hoc subgroup analysis showed statistical significant interaction between age and treatment strategy on outcome (p=0.02).ConclusionsAfter 2 years follow-up, no difference in incidence of death or reinfarction was seen between early to late invasive strategy. These findings are in line with results of other studies with longer follow-up. Older patients seem to benefit more from early invasive treatment.
Mechanisms of the deep, slow-wave, sleep-related increase of upper airway muscle tone in healthy humans
Authors: Hicks Amelia , Cori Jennifer M. , Jordan Amy S. , Nicholas Christian L. , Kubin Leszek , Semmler John G. , Malhotra Atul , McSharry David G. P. , Trinder John A. 
Published: March 2017

Upper airway muscle activity is reportedly elevated during slow-wave sleep (SWS) when compared with lighter sleep stages. To uncover the possible mechanisms underlying this elevation, we explored the correlation between different indices of central and reflex inspiratory drive, such as the changes in airway pressure and end-expiratory CO2and the changes in the genioglossus (GG) and tensor palatini (TP) muscle activity accompanying transitions from the lighter N2 to the deeper N3 stage of non-rapid eye movement (NREM) sleep in healthy young adult men. Forty-six GG and 38 TP continuous electromyographic recordings were obtained from 16 men [age: 20 ± 2.5 (SD) yr; body mass index: 22.5 ± 1.8 kg/m2] during 32 transitions from NREM stages N2 to N3. GG but not TP activity increased following transition into N3 sleep, and the increase was positively correlated with more negative airway pressure, increased end-tidal CO2, increased peak inspiratory flow, and increased minute ventilation. None of these correlations was statistically significant for TP. Complementary GG and TP single motor unit analysis revealed a mild recruitment of GG units and derecruitment of TP units during the N2 to N3 transitions. These findings suggest that, in healthy individuals, the increased GG activity during SWS is driven primarily by reflex stimulation of airway mechanoreceptors and central chemoreceptors.NEW & NOTEWORTHY The characteristic increase in the activity of the upper airway dilator muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulation of airway mechanoreceptors and central chemoreceptors. No evidence was found for the presence of a central SWS-specific drive stimulating genioglossus activity in young healthy individuals. However, it remains to be determined whether a central drive exists in obstructive sleep apnea patients.
Adaptive Reprogramming of De Novo Pyrimidine Synthesis Is a Metabolic Vulnerability in Triple-Negative Breast Cancer
Authors: Brown Kristin K. , Spinelli Jessica B. , Asara John M. , Toker Alex 
Published: March 2017

Abstract
Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC), and strategies to circumvent resistance are required. Using in vitro and in vivo metabolic profiling of TNBC cells, we show that an increase in the abundance of pyrimidine nucleotides occurs in response to chemotherapy exposure. Mechanistically, elevation of pyrimidine nucleotides induced by chemotherapy is dependent on increased activity of the de novo pyrimidine synthesis pathway. Pharmacologic inhibition of de novo pyrimidine synthesis sensitizes TNBC cells to genotoxic chemotherapy agents by exacerbating DNA damage. Moreover, combined treatment with doxorubicin and leflunomide, a clinically approved inhibitor of the de novo pyrimidine synthesis pathway, induces regression of TNBC xenografts. Thus, the increase in pyrimidine nucleotide levels observed following chemotherapy exposure represents a metabolic vulnerability that can be exploited to enhance the efficacy of chemotherapy for the treatment of TNBC.
Significance: The prognosis for patients with TNBC with residual disease after chemotherapy is poor. We find that chemotherapy agents induce adaptive reprogramming of de novo pyrimidine synthesis and show that this response can be exploited pharmacologically, using clinically approved inhibitors of de novo pyrimidine synthesis, to sensitize TNBC cells to chemotherapy. Cancer Discov; 7(4); 391–9. ©2017 AACR.
See related article by Mathur et al., p. 380.
This article is highlighted in the In This Issue feature, p. 339
PTEN Regulates Glutamine Flux to Pyrimidine Synthesis and Sensitivity to Dihydroorotate Dehydrogenase Inhibition
Authors: Mathur Deepti , Stratikopoulos Elias , Ozturk Sait , Steinbach Nicole , Pegno Sarah , Schoenfeld Sarah , Yong Raymund , Murty Vundavalli V. , Asara John M. , Cantley Lewis C. , Parsons Ramon 
Published: March 2017

Abstract
Metabolic changes induced by oncogenic drivers of cancer contribute to tumor growth and are attractive targets for cancer treatment. Here, we found that increased growth of PTEN-mutant cells was dependent on glutamine flux through the de novo pyrimidine synthesis pathway, which created sensitivity to the inhibition of dihydroorotate dehydrogenase, a rate-limiting enzyme for pyrimidine ring synthesis. S-phase PTEN-mutant cells showed increased numbers of replication forks, and inhibitors of dihydroorotate dehydrogenase led to chromosome breaks and cell death due to inadequate ATR activation and DNA damage at replication forks. Our findings indicate that enhanced glutamine flux generates vulnerability to dihydroorotate dehydrogenase inhibition, which then causes synthetic lethality in PTEN-deficient cells due to inherent defects in ATR activation. Inhibition of dihydroorotate dehydrogenase could thus be a promising therapy for patients with PTEN-mutant cancers.
Significance: We have found a prospective targeted therapy for PTEN-deficient tumors, with efficacy in vitro and in vivo in tumors derived from different tissues. This is based upon the changes in glutamine metabolism, DNA replication, and DNA damage response which are consequences of inactivation of PTEN. Cancer Discov; 7(4); 380–90. ©2017 AACR.
See related article by Brown et al., p. 391.
This article is highlighted in the In This Issue feature, p. 339
MicroRNA-150 Modulates Ischemia-Induced Neovascularization in Atherosclerotic Conditions
Authors: Desjarlais Michel , Dussault Sylvie , Dhahri Wahiba , Mathieu Raphael , Rivard Alain 
Published: March 2017

Objective—
Hypercholesterolemia is an atherosclerotic condition that is associated with impaired neovascularization in response to ischemia. This study sought to define the role of microRNAs in that pathophysiology.

Approach and Results—

Next-generation sequencing and quantitative reverse transcription polymerase chain reaction analyses identified miR-150 as a proangiogenic microRNA, which expression is significantly reduced in the ischemic muscles of hypercholesterolemic apolipoprotein E–deficient (ApoE
−/−
) mice, and in human umbilical vein endothelial cells exposed to oxidized low-density lipoprotein. Forced expression of miR-150 using a miR mimic could rescue oxidized low-density lipoprotein–mediated impairment of endothelial cell migration and tubule formation in vitro. In a mouse model of hindlimb ischemia, intramuscular injection of miR-150 mimic restored blood flow recuperation, vascular densities in ischemic muscles, and functional mobility in ApoE
−/−
mice. Treatment of ApoE
−/−
mice with miR-150 also increased the number and the activities of proangiogenic cells. miR-150 targets SRC kinase signaling inhibitor 1, an important regulator of Src (proto-oncogene tyrosine-protein kinase Src) activity. Here we found that hypercholesterolemia and oxidized low-density lipoprotein exposure are associated with increased SRC kinase signaling inhibitor 1 expression and decreased Src activity. However, treatment with miR-150 mimic reduces SRC kinase signaling inhibitor 1 expression and restores Src and downstream endothelial nitric oxide synthase and Akt (protein kinase B) activities both in vitro and in vivo. We also demonstrate the interrelation between miR-150 and SRC kinase signaling inhibitor 1 and their importance for endothelial cell angiogenic activities.

Conclusions—
Hypercholesterolemia is associated with reduced expression of miR-150, impaired Src signaling, and inefficient neovascularization in response to ischemia. Forced expression of miR-150 using a miR mimic could constitute a novel therapeutic strategy to improve ischemia-induced neovascularization in atherosclerotic conditions.
RXR Ligands Negatively Regulate Thrombosis and Hemostasis
Authors: Unsworth Amanda J. , Flora Gagan D. , Sasikumar Parvathy , Bye Alexander P. , Sage Tanya , Kriek Neline , Crescente Marilena , Gibbins Jonathan M. 
Published: March 2017

Objective—
Platelets have been found to express intracellular nuclear receptors including the retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2; however, the effects on responses to other platelet agonists and the underlying mechanism have not been fully characterized.

Approach and Results—

The effect of 9-
cis
-retinoic acid, docosahexaenoic acid and methoprene acid on collagen receptor (glycoprotein VI [GPVI]) agonists and thrombin-stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilization, integrin αIIbβ3 outside-in signaling and thrombus formation in vitro and in vivo were determined. Treatment of platelets with RXR ligands resulted in attenuation of platelet functional responses after stimulation by GPVI agonists or thrombin and inhibition of integrin αIIbβ3 outside-in signaling. Treatment with 9-
cis
-retinoic acid caused inhibition of thrombus formation in vitro and an impairment of thrombosis and hemostasis in vivo. Both RXR ligands stimulated protein kinase A activation, measured by VASP S157 phosphorylation, that was found to be dependent on both cAMP and nuclear factor κ-light-chain-enhancer of activated B cell activity.

Conclusions—
This study identifies a widespread, negative regulatory role for RXR in the regulation of platelet functional responses and thrombus formation and describes novel events that lead to the upregulation of protein kinase A, a known negative regulator of many aspects of platelet function. This mechanism may offer a possible explanation for the cardioprotective effects described in vivo after treatment with RXR ligands.
Heart Failure Incidence and Mortality in the Southern Community Cohort Study
Authors: Akwo Elvis A. , Kabagambe Edmond K. , Wang Thomas J. , Harrell Frank E. , Blot William J. , Mumma Michael , Gupta Deepak K. , Lipworth Loren 
Published: March 2017

Background—
There is a paucity of data on heart failure (HF) incidence among low-income and minority populations. Our objective was to investigate HF incidence and post-HF survival by race and sex among low-income adults in the southeastern United States.

Methods and Results—

Participants were 27 078 white and black men and women enrolled during 2002 to 2009 in the SCCS (Southern Community Cohort Study) who had no history of HF and were receiving Centers for Medicare and Medicaid Services. Incident HF diagnoses through December 31, 2010 were ascertained using
International Classification of Diseases
9th Revision codes 428.x via linkage with Centers for Medicare and Medicaid Services research files. Most participants were black (68.8%), women (62.6%), and earned <$15 000/y (69.7%); mean age was 55.5 (10.4) years. Risk factors for HF were common: hypertension (62.5%), diabetes mellitus (26.5%), myocardial infarction (8.6%), and obesity (44.8%). Over a median follow-up of 5.2 years, 4341 participants were diagnosed with HF. The age-standardized incidence rates were 34.8, 37.3, 34.9, and 35.6 /1000 person-years in white women, white men, black men, and black women, respectively, remarkably higher than previously reported. Among HF cases, 952 deaths occurred over a median follow-up of 2.3 years. Men had lower survival; hazard ratios and 95% confidence intervals were 1.63 (1.27–2.08), 1.38 (1.11–1.72), and 0.90 (0.73–1.12) for white men, black men, and black women compared with white women.

Conclusions—
In this low-income population, HF incidence was higher for all race–sex groups than previously reported in other cohorts. The SCCS is a unique resource to investigate determinants of HF risk in a segment of the population underrepresented in other existing cohorts.
Rheumatic Heart Disease Severity, Progression and Outcomes: A Multi‐State Model
Authors: Cannon Jeffrey , Roberts Kathryn , Milne Catherine , Carapetis Jonathan R. 
Published: March 2017

Background

Rheumatic heart disease (
RHD
) remains a disease of international importance, yet little has been published about disease progression in a contemporary patient cohort. Multi‐state models provide a well‐established method of estimating rates of transition between disease states, and can be used to evaluate the cost‐effectiveness of potential interventions. We aimed to create a multi‐state model for
RHD
progression using serial clinical data from a cohort of Australian patients.

Methods and Results

The Northern Territory
RHD
register was used to identify all Indigenous residents diagnosed with
RHD
between the ages of 5 and 24 years in the time period 1999–2012. Disease severity over time, surgeries, and deaths were evaluated for 591 patients. Of 96 (16.2%) patients with severe
RHD
at diagnosis, 50% had proceeded to valve surgery by 2 years, and 10% were dead within 6 years. Of those diagnosed with moderate
RHD
, there was a similar chance of disease regression or progression over time. Patients with mild
RHD
at diagnosis were the most stable, with 64% remaining mild after 10 years; however, 11.4% progressed to severe
RHD
and half of these required surgery.

Conclusions

The prognosis of young Indigenous Australians diagnosed with severe
RHD
is bleak; interventions must focus on earlier detection and treatment if the observed natural history is to be improved. This multi‐state model can be used to predict the effect of different interventions on disease progression and the associated costs.
An Anomalous Genesis Potential Index for MJO Modulation of Tropical Cyclones
Authors: Wang Bin , Moon Ja-Yeon 
Published: March 2017

Abstract
Modulation of tropical cyclone (TC) genesis by the Madden–Julian oscillation (MJO) has been quantitatively diagnosed by using a climatological genesis potential index (GPI). Analysis of TC genesis during November–April of 1979–2014 indicates the most effective factors controlling intraseasonal TC genesis are 850-hPa relative vorticity weighted by the Coriolis parameter fζr850 and 500-hPa vertical motion ω500. The total vertical wind shear and maximum potential intensity are unimportant, and the role of 600-hPa relative humidity is greatly represented by ω500. The MJO modulates TC genesis primarily through changing low-level vorticity induced by its Rossby wave gyres and meridional shears of equatorial zonal winds. A new intraseasonal GPI (ISGPI) is proposed to quantify the MJO’s modulation of TC genesis. The ISGPI significantly improves representation of intraseasonal variation of TC genesis in the tropics and in each subregion of the southern Indian Ocean, Australian monsoon, and South Pacific. In the hot spots of the Southern Hemisphere TC genesis zone, the probability of TC genesis can differ by a factor of 5–19 as a result of MJO modulation. The results suggest that the large-scale factors controlling TC genesis may vary with different time scales, and the climatological GPI may not be quite applicable for diagnoses of climate variability and future change of TC genesis potential. To simulate realistic impacts of the MJO on TC genesis, general circulation models must reproduce not only realistic eastward propagation but also the MJO low-level circulation structure. Application of the new ISGPI may have a large potential to improve dynamical subseasonal prediction of TC genesis.
Measurement of Cough Aerodynamics in Healthy Adults
Authors: Feinstein Aaron J. , Zhang Zhaoyan , Chhetri Dinesh K. , Long Jennifer 
Published: March 2017

Importance: Cough is a critical human reflex and also among the most frequent symptoms in medicine. Despite the prevalence of disordered cough in laryngeal pathologies, comprehensive and quantitative evaluation of cough in these patients is lacking. Objective: Herein we seek to establish normative values for cough aerodynamics to provide a population standard for reference in future studies. Design, Setting, and Participants: Healthy subjects were recruited from an outpatient clinic to perform voluntary cough. Subjects were instructed on the technique for maximal voluntary cough production with measurements recorded on pneumotachograph. Fifty-two subjects were studied, including 29 women and 23 men with a mean age of 51.6 and 52.3 years, respectively. Main Outcomes and Measures: Cough peak airflow, peak pressure, and expiratory rise time. Results were stratified by age, gender, and height. Results: Peak airflow demonstrated significant differences across age, gender, and height, with flow increasing according to increasing height. Peak cough pressure also increased with height and was significantly greater in males versus females. Expiratory rise time, the time from glottal opening to peak airflow, did not vary with age or height but was statistically significantly longer in women. Conclusions: Cough aerodynamics can be readily measured objectively in the outpatient setting. Expiratory rise time, peak flow, and peak pressure are important aspects of each cough epoch. Normative data provided herein can be used for future studies of patients with laryngotracheal disorders, and these cough parameters may prove to be simple, accessible, and repeatable outcome measures.
The Effects of On-Pump and Off-Pump Coronary Artery Bypass Surgery on Respiratory Function in the Early Postoperative Period
Authors: Chiarenza Federica , Tsoutsouras Theodoros , Cassisi Cesare , Santonocito Cristina , Gerry Stephen , Astuto Marinella , George Shane , Sanfilippo Filippo 
Published: March 2017

Background: Respiratory complications are common after cardiac surgery and the use of extracorporeal circulation is one of the main causes of lung injury. We hypothesized a better postoperative respiratory function in off-pump coronary artery bypass grafting (OPCABG) as compared with “on-pump coronary artery bypass grafting” (ONCABG). Methods: This is a retrospective, single-center study at a cardiothoracic intensive care unit (ICU) in a tertiary university hospital. Consecutive data on 339 patients undergoing elective CABG (n = 215 ONCABG, n = 124 OPCABG) were collected for 1 year from the ICU electronic medical records. We compared respiratory variables (Pao2, Pao2/Fio2 ratio, Sao2, and Paco2) at 7 predefined time points (ICU admission, postoperative hours 1, 3, 6, 12, 18, and 24). We also evaluated time to extubation, rates of reintubation, and use of noninvasive ventilation (NIV). We used mixed-effects linear regression models (with time as random effect for clustering of repeated measures) adjusted for a predetermined set of covariates. Results: The values of Pao2 and Pao2/Fio2 were significantly higher in the OPCABG group only at ICU admission (mean differences: 9.7 mm Hg, 95% confidence interval [CI] 3.1-16.2; and 27, 95% CI 6.1-47.7, respectively). The OPCABG group showed higher Paco2, overall ( P = .02) and at ICU admission (mean difference 1.8 mm Hg, 95% CI: 0.6-3), although mean values were always within normal range in both groups. No differences were seen in Sao2 values, time to extubation, rate of reintubation rate, and use of postoperative NIV. Extubation rate was higher in OPCABG only at postoperative hour 12 (92% vs ONCABG 82%, P = .02). Conclusion: The OPCABG showed only marginal improvements of unlikely clinical meaning in oxygenation as compared to ONCABG in elective low-risk patients.