bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare-seeking behaviour, barriers and mental health of non-domestic migrant workers in Singapore
Authors: Ang Jia Wei , Chia Colin , Koh Calvin J , Chua Brandon W B , Narayanaswamy Shyamala , Wijaya Limin , Chan Lai Gwen , Goh Wei Leong , Vasoo Shawn 
Published: March 2017

BackgroundLow-wage migrant workers are vulnerable to healthcare inequities. We sought to identify potential barriers to healthcare and risk factors for mental health issues in non-domestic migrant workers in Singapore, and identify high-risk subgroups.MethodsA cross-sectional, interviewer-administered survey of 433 non-domestic migrant workers was conducted at subsidised clinics and a foreign worker dormitory from July to August 2016. Questions assessed healthcare usage patterns, affordability issues, barriers to care and psychological distress using a validated screening scale (Kessler-6).FindingsBangladeshi workers surveyed were more likely to be single, have more financial dependents, a lower level of education and salary and pay higher agent fees (p<0.01). 61.4% of workers reported that they had insurance, but had poor understanding of whether it covered inpatient/outpatient expenses. The majority of workers had not, or were not sure if they had, received information about company-bought insurance (72.4%). Among those who had, most reported that information was not in their native language (67.7%). Non-specific psychological distress was found in 21.9%, as estimated by the Kessler-6 scale. Multivariate analysis found that psychological distress was independently associated with Bangladeshi nationals (OR 2.98, 95% CI 1.58 to 5.62; p=0.001) and previous experience of financial barriers to healthcare (OR 3.86, 95% CI 2.25 to 6.62; p<0.0001).InterpretationWe identified gaps in non-domestic migrant workers' knowledge of healthcare coverage, and substantial financial barriers to healthcare. The Bangladeshi population in our study was at higher risk of such barriers and psychological distress. These represent areas for further research and intervention.
Disposable versus non-disposable tonometer prisms: a UK national survey
Authors: Jasani Kirti M , Putri Christine , Pearl Amy , Sattar Nayeem , Mercieca Karl , Spaeth George , Bhan-Bhargava Archana 
Published: March 2017

PurposeTo determine the prevalence of disposable tonometer versus non-disposable tonometer use in the UK and to determine methods of decontamination and frequency of replacement of prisms.A total of 137 ophthalmology departments were interviewed by telephone using a structured questionnaire. The main outcome measured were:types of tonometer prisms used in clinic (disposable, non-disposable and/or other)average disposable prisms used per clinic sessionaverage lifespan of non-disposable prismsprism preference by glaucoma and other teams within department.A cost and benefit analysis was then performed on the data acquired.ResultsOne hundred and fifty-five departments were identified for the survey. Of these, 137 (88.3%) responded. Eighty-one departments (59.1%) used Tonosafe prisms alone, whereas 22 departments (16.1%) used Goldmann non-disposable prisms exclusively. Thirty-five departments (64%) on average have a change rate of 26.5% per year (range: 0–100, median: 20) attributed to damage, loss or theft. Sixteen departments (29%) reported that prisms were used until damaged or lost. Four departments (7%) were uncertain of their prism usage and could not provide further information.ConclusionsMajority of eye departments in the UK opt for disposable prisms. This survey shows the perceived cost-effectiveness of disposable prisms is overestimated when the true cost of disinfection and damage is taken into account. Significant cost savings coupled with the low risk of infectivity (if decontaminated properly) should prompt clinicians and ophthalmic departments worldwide to reconsider the use of non-disposable prisms.
Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions
Authors: Durgin Brittany G. , Cherepanova Olga A. , Gomez Delphine , Karaoli Themistoclis , Alencar Gabriel F. , Butcher Joshua T. , Zhou Yu-Qing , Bendeck Michelle P. , Isakson Brant E. , Owens Gary K. , Connelly Jessica J. 
Published: March 2017

Atherosclerotic plaque rupture with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke. Although smooth muscle cells (SMCs) produce and respond to collagens in vitro, there is no direct evidence in vivo that SMCs are a crucial source of collagens and that this impacts lesion development or fibrous cap formation. We sought to determine how conditional SMC-specific knockout of collagen type XV (COL15A1) in SMC lineage tracing mice affects advanced lesion formation given that 1) we have previously identified a Col15a1 sequence variant associated with age-related atherosclerosis, 2) COL15A1 is a matrix organizer enhancing tissue structural integrity, and 3) small interfering RNA-mediated Col15a1 knockdown increased migration and decreased proliferation of cultured human SMCs. We hypothesized that SMC-derived COL15A1 is critical in advanced lesions, specifically in fibrous cap formation. Surprisingly, we demonstrated that SMC-specific Col15a1 knockout mice fed a Western diet for 18 wk failed to form advanced lesions. SMC-specific Col15a1 knockout resulted in lesions reduced in size by 78%, with marked reductions in numbers and proliferating SMCs, and lacked a SMC and extracellular matrix-rich lesion or fibrous cap. In vivo RNA-seq analyses on SMC Col15a1 knockout and wild-type lesions suggested that a mechanism for these effects is through global repression of multiple proatherogenic inflammatory pathways involved in lesion development. These results provide the first direct evidence that a SMC-derived collagen, COL15A1, is critical during lesion pathogenesis, but, contrary to expectations, its loss resulted in marked attenuation rather than exacerbation of lesion pathogenesis. NEW & NOTEWORTHY We report the first direct in vivo evidence that a smooth muscle cell (SMC)-produced collagen, collagen type XV (COL15A1), is critical for atherosclerotic lesion development. SMC Col15a1 knockout markedly attenuated advanced lesion formation, likely through reducing SMC proliferation and impairing multiple proatherogenic inflammatory processes.
Dynamics of middle cerebral artery blood flow velocity during moderate-intensity exercise
Authors: Billinger Sandra A. , Craig Jesse C. , Kwapiszeski Sarah J. , Sisante Jason-Flor V. , Vidoni Eric D. , Maletsky Rebecca , Poole David C. 
Published: March 2017

The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAVresponse profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAVas supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAVbaseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAVthat was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAVduring exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease.NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.
Exercise-induced dehydration alters pulmonary function but does not modify airway responsiveness to dry air in athletes with mild asthma
Authors: Simpson A. J. , Romer L. M. , Kippelen P. 
Published: March 2017

Local airway water loss is the main physiological trigger for exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effects of whole body water loss on airway responsiveness and pulmonary function in athletes with mild asthma and/or EIB. Ten recreational athletes with a medical diagnosis of mild asthma and/or EIB completed a randomized, crossover study. Pulmonary function tests, including spirometry, whole body plethysmography, and diffusing capacity of the lung for carbon monoxide (DlCO), were conducted before and after three conditions: 1) 2 h of exercise in the heat with no fluid intake (dehydration), 2) 2 h of exercise with ad libitum fluid intake (control), and 3) a time-matched rest period (rest). Airway responsiveness was assessed 2 h postexercise/rest via eucapnic voluntary hyperpnea (EVH) to dry air. Exercise in the heat with no fluid intake induced a state of mild dehydration, with a body mass loss of 2.3 ± 0.8% (SD). After EVH, airway narrowing was not different between conditions: median (interquartile range) maximum fall in forced expiratory volume in 1 s was 13 (7–15)%, 11 (9–24)%, and 12 (7–20)% in dehydration, control, and rest conditions, respectively. Dehydration caused a significant reduction in forced vital capacity (300 ± 190 ml, P = 0.001) and concomitant increases in residual volume (260 ± 180 ml, P = 0.001) and functional residual capacity (260 ± 250 ml, P = 0.011), with no change in DlCO. Mild exercise-induced dehydration does not exaggerate airway responsiveness to dry air in athletes with mild asthma/EIB but may affect small airway function.NEW & NOTEWORTHY This study is the first to investigate the effect of whole body dehydration on airway responsiveness. Our data suggest that the airway response to dry air hyperpnea in athletes with mild asthma and/or exercise-induced bronchoconstriction is not exacerbated in a state of mild dehydration. On the basis of alterations in lung volumes, however, exercise-induced dehydration appears to compromise small airway function.
Local Activation of p53 in the Tumor Microenvironment Overcomes Immune Suppression and Enhances Antitumor Immunity
Authors: Guo Gang , Yu Miao , Xiao Wei , Celis Esteban , Cui Yan 
Published: March 2017

Abstract
Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor-infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma. Maneuvers that recruit leukocytes to TME, such as TLR3 ligand in B16 tumors, greatly enhanced nutlin-induced antitumor immunity and tumor control. Mechanistically, nutlin-3a–induced antitumor immunity was contingent on two nonredundant but immunologically synergistic p53-dependent processes: reversal of immunosuppression in the TME and induction of tumor immunogenic cell death, leading to activation and expansion of polyfunctional CD8 CTLs and tumor regression. Our study demonstrates that unlike conventional tumoricidal therapies, which rely on effective p53 targeting in each tumor cell and often associate with systemic toxicity, this immune-based strategy requires only limited local p53 activation to alter the immune landscape of TME and subsequently amplify immune response to systemic antitumor immunity. Hence, targeting the p53 pathway in TME can be exploited to reverse immunosuppression and augment therapeutic benefits beyond tumoricidal effects to harness tumor-specific, durable, and systemic antitumor immunity with minimal toxicity. Cancer Res; 77(9); 2292–305. ©2017 AACR.
A Phase I/Ib Study of Enzalutamide Alone and in Combination with Endocrine Therapies in Women with Advanced Breast Cancer
Authors: Schwartzberg Lee S. , Yardley Denise A. , Elias Anthony D. , Patel Manish , LoRusso Patricia , Burris Howard A. , Gucalp Ayca , Peterson Amy C. , Blaney Martha E. , Steinberg Joyce L. , Gibbons Jacqueline A. , Traina Tiffany A. 
Published: March 2017

AbstractPurpose: Several lines of evidence support targeting the androgen signaling pathway in breast cancer. Enzalutamide is a potent inhibitor of androgen receptor signaling. Preclinical data in estrogen-expressing breast cancer models demonstrated activity of enzalutamide monotherapy and enhanced activity when combined with various endocrine therapies (ET). Enzalutamide is a strong cytochrome P450 3A4 (CYP3A4) inducer, and ETs are commonly metabolized by CYP3A4. The pharmacokinetic (PK) interactions, safety, and tolerability of enzalutamide monotherapy and in combination with ETs were assessed in this phase I/Ib study.Experimental Design: Enzalutamide monotherapy was assessed in dose-escalation and dose-expansion cohorts of patients with advanced breast cancer. Additional cohorts examined effects of enzalutamide on anastrozole, exemestane, and fulvestrant PK in patients with estrogen receptor–positive/progesterone receptor–positive (ER+/PgR+) breast cancer.Results: Enzalutamide monotherapy (n = 29) or in combination with ETs (n = 70) was generally well tolerated. Enzalutamide PK in women was similar to prior data on PK in men with prostate cancer. Enzalutamide decreased plasma exposure to anastrozole by approximately 90% and exemestane by approximately 50%. Enzalutamide did not significantly affect fulvestrant PK. Exposure of exemestane 50 mg/day given with enzalutamide was similar to exemestane 25 mg/day alone.Conclusions: These results support a 160 mg/day enzalutamide dose in women with breast cancer. Enzalutamide can be given in combination with fulvestrant without dose modifications. Exemestane should be doubled from 25 mg/day to 50 mg/day when given in combination with enzalutamide; this combination is being investigated in a randomized phase II study in patients with ER+/PgR+ breast cancer. Clin Cancer Res; 23(15); 4046–54. ©2017 AACR.
Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma
Authors: Zhang Bin , Tian Jie , Dong Di , Gu Dongsheng , Dong Yuhao , Zhang Lu , Lian Zhouyang , Liu Jing , Luo Xiaoning , Pei Shufang , Mo Xiaokai , Huang Wenhui , Ouyang Fusheng , Guo Baoliang , Liang Long , Chen Wenbo , Liang Changhong , Zhang Shuixing 
Published: March 2017

Abstract
Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC).
Experimental Design: One-hundred and eighteen patients (training cohort: n = 88; validation cohort: n = 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features for progression-free survival (PFS) nomograms. Nomogram discrimination and calibration were evaluated. Associations between radiomics features and clinical data were investigated using heatmaps.
Results: The radiomics signatures were significantly associated with PFS. A radiomics signature derived from joint CET1-w and T2-w images showed better prognostic performance than signatures derived from CET1-w or T2-w images alone. One radiomics nomogram combined a radiomics signature from joint CET1-w and T2-w images with the TNM staging system. This nomogram showed a significant improvement over the TNM staging system in terms of evaluating PFS in the training cohort (C-index, 0.761 vs. 0.514; P &lt; 2.68 × 10−9). Another radiomics nomogram integrated the radiomics signature with all clinical data, and thereby outperformed a nomogram based on clinical data alone (C-index, 0.776 vs. 0.649; P &lt; 1.60 × 10−7). Calibration curves showed good agreement. Findings were confirmed in the validation cohort. Heatmaps revealed associations between radiomics features and tumor stages.
Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies. Clin Cancer Res; 23(15); 4259–69. ©2017 AACR.
Ezetimibe Increases Endogenous Cholesterol Excretion in Humans
Authors: Lin Xiaobo , Racette Susan B. , Ma Lina , Wallendorf Michael , Ostlund Richard E. 
Published: March 2017

Objective—
Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool.

Approach and Results—

In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d
7
in a lipid emulsion and dietary cholesterol with cholesterol-d
5
and sitostanol-d
4
solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE,
P
<0.0001) and low-density lipoprotein cholesterol 19.8±1.9% (
P
=0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% (
P
<0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% (
P
<0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% (
P
=0.0096). Fecal bile acids were unchanged.

Conclusions—
Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis.

Clinical Trials
Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01603758.
Soleus Atrophy Is Common After the Nonsurgical Treatment of Acute Achilles Tendon Ruptures: A Randomized Clinical Trial Comparing Surgical and Nonsurgical Functional Treatments
Authors: Heikkinen Juuso , Lantto Iikka , Flinkkila Tapio , Ohtonen Pasi , Niinimaki Jaakko , Siira Pertti , Laine Vesa , Leppilahti Juhana 
Published: March 2017

Background:It remains controversial whether nonsurgical or surgical treatment provides better calf muscle strength recovery after an acute Achilles tendon rupture (ATR). Recent evidence has suggested that surgery might surpass nonsurgical treatment in restoring strength after an ATR.Purpose:To assess whether magnetic resonance imaging (MRI) findings could explain calf muscle strength deficits and the difference between nonsurgical and surgical treatments in restoring calf muscle strength.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:From 2009 to 2013, 60 patients with acute ATRs were randomized to surgery or nonsurgical treatment with an identical rehabilitation protocol. The primary outcome measure was the volume of calf muscles assessed using MRI at 3 and 18 months. The secondary outcome measures included fatty degeneration of the calf muscles and length of the affected Achilles tendon. Additionally, isokinetic plantarflexion strength was measured in both legs.Results:At 3 months, the study groups showed no differences in muscle volumes or fatty degeneration. However, at 18 months, the mean differences between affected and healthy soleus muscle volumes were 83.2 cm3(17.7%) after surgery and 115.5 cm3(24.8%) after nonsurgical treatment (difference between means, 33.1 cm3; 95% CI, 1.3-65.0; P = .042). The study groups were not substantially different in the volumes or fatty degeneration of other muscles. From 3 to 18 months, compensatory hypertrophy was detected in the flexor hallucis longus (FHL) and deep flexors in both groups. In the nonsurgical treatment group, the mean difference between affected and healthy FHL muscle volumes was −9.3 cm3(12%) and in the surgical treatment group was −8.4 cm3(10%) ( P ≤ .001). At 18 months, Achilles tendons were, on average, 19 mm longer in patients treated nonsurgically compared with patients treated surgically ( P < .001). At 18 months, surgically treated patients demonstrated 10% to 18% greater strength results ( P = .037). Calf muscle isokinetic strength deficits for the entire range of ankle motion correlated with soleus atrophy (ρ = 0.449-0.611; P < .001).Conclusion:Treating ATRs nonsurgically with a functional rehabilitation protocol resulted in greater soleus muscle atrophy compared with surgical treatment. The mean Achilles tendon length was 19 mm longer after nonsurgical treatment than after the surgical treatment of ATRs. These structural changes partly explained the 10% to 18% greater calf muscle strength observed in patients treated with surgery compared with those treated nonsurgically.Registration:NCT02012803 ( ClinicalTrials.gov identifier).