bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acupuncture with Or without Combined Auricular Acupuncture for Insomnia: A Randomised, Waitlist-Controlled Trial
Authors: Chung Ka-Fai , Yeung Wing-Fai , Yu Branda Yee-Man , Leung Feona Chung-Yin , Zhang Shi-Ping , Zhang Zhang-Jin , Ng Roger Man-Kin , Yiu Gar-Chung 
Published: August 2018

Background Few high-quality, large-scale, controlled trials comparing the effectiveness and safety of acupuncture, auricular acupuncture and combined acupuncture treatment for insomnia are available. Objective To carry out a randomised, assessor-blinded, waitlist-controlled trial to test the superiority of combination treatment. Methods After in-person and polysomnography screening, 224 subjects (mean age 53.4 years; 75.4% female) with DSM-5 insomnia disorder, who were free from major psychiatric disorders and with sleep-diary-derived sleep efficiency averaged over 1 week of <85%, were randomised to acupuncture alone, acupuncture plus auricular acupuncture (combination treatment), or a waitlist in a 3:3:1 ratio. Standardised acupuncture and combination treatment were provided three times weekly for 3 weeks. The primary outcome was sleep-diary-derived sleep efficiency. Secondary outcomes included wrist actigraphy and self-reported scales on insomnia, anxiety and depression, fatigue, sleepiness and functioning. Assessments were conducted at baseline, 1 week, 4 weeks and 13 weeks after treatment. Participants on the waitlist were re-randomised to receive acupuncture or combination treatment after the second post-baseline assessment. Results There was no significant difference between acupuncture and combination treatment in the primary outcome and most secondary outcomes at all time points. However, both treatments were better than waitlist in reducing insomnia, anxiety/depressive symptoms and fatigue, and improving function. Within-group improvements were maintained at 13 weeks after treatment. Of 260 adverse events, 243 were mild (93.5%). Discontinuation due to adverse events was 2.1% and 3.1% for acupuncture and combination treatment, respectively. Conclusions Limited by short-term treatment and follow-up, the attempt to augment acupuncture by auricular acupuncture was not supported. Acupuncture and combination treatment were safe and had mild hypnotic effects, which lasted for at least 13 weeks. Trial Registration Number NCT01891097; Results.
Value of hospital resources for effective pressure injury prevention: a cost-effectiveness analysis
Authors: Padula William V , Pronovost Peter J , Makic Mary Beth F , Wald Heidi L , Moran Dane , Mishra Manish K , Meltzer David O 
Published: August 2018

ObjectiveHospital-acquired pressure injuries are localised skin injuries that cause significant mortality and are costly. Nursing best practices prevent pressure injuries, including time-consuming, complex tasks that lack payment incentives. The Braden Scale is an evidence-based stratification tool nurses use daily to assess pressure-injury risk. Our objective was to analyse the cost-utility of performing repeated risk-assessment for pressure-injury prevention in all patients or high-risk groups.DesignCost-utility analysis using Markov modelling from US societal and healthcare sector perspectives within a 1-year time horizon.SettingPatient-level longitudinal data on 34 787 encounters from an academic hospital electronic health record (EHR) between 2011 and 2014, including daily Braden scores. Supervised machine learning simulated age-adjusted transition probabilities between risk levels and pressure injuries.ParticipantsHospitalised adults with Braden scores classified into five risk levels: very high risk (6–9), high risk (10–11), moderate risk (12–14), at-risk (15–18), minimal risk (19–23).InterventionsStandard care, repeated risk assessment in all risk levels or only repeated risk assessment in high-risk strata based on machine-learning simulations.Main outcome measuresCosts (2016 $US) of pressure-injury treatment and prevention, and quality-adjusted life years (QALYs) related to pressure injuries were weighted by transition probabilities to calculate the incremental cost-effectiveness ratio (ICER) at $100 000/QALY willingness-to-pay. Univariate and probabilistic sensitivity analyses tested model uncertainty.ResultsSimulating prevention for all patients yielded greater QALYs at higher cost from societal and healthcare sector perspectives, equating to ICERs of $2000/QALY and $2142/QALY, respectively. Risk-stratified follow-up in patients with Braden scores <15 dominated standard care. Prevention for all patients was cost-effective in >99% of probabilistic simulations.ConclusionOur analysis using EHR data maintains that pressure-injury prevention for all inpatients is cost-effective. Hospitals should invest in nursing compliance with international prevention guidelines.
Assessment of cardiovascular risk and preparticipation screening protocols in masters athletes: the Masters Athlete Screening Study (MASS): a cross-sectional study
Authors: Morrison Barbara N , McKinney James , Isserow Saul , Lithwick Daniel , Taunton Jack , Nazzari Hamed , De Souza Astrid M , Heilbron Brett , Cater Carlee , MacDonald Mackenzie , Hives Benjamin A , Warburton Darren E R 
Published: August 2018

BackgroundUnderlying coronary artery disease (CAD) is the primary cause of sudden cardiac death in masters athletes (>35 years). Preparticipation screening may detect cardiovascular disease; however, the optimal screening method is undefined in this population. The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) and the American Heart Association (AHA) Preparticipation Screening Questionnaire are often currently used; however, a more comprehensive risk assessment may be required. We sought to ascertain the cardiovascular risk and to assess the effectiveness of screening tools in masters athletes.MethodsThis cross-sectional study performed preparticipation screening on masters athletes, which included an ECG, the AHA 14-element recommendations and Framingham Risk Score (FRS). If the preparticipation screening was abnormal, further evaluations were performed. The effectiveness of the screening tools was determined by their positive predictive value (PPV).Results798 athletes were included in the preparticipation screening analysis (62.7% male, 54.6±9.5 years, range 35–81). The metabolic equivalent task hours per week was 80.8±44.0, and the average physical activity experience was 35.1±14.8 years. Sixty-four per cent underwent additional evaluations. Cardiovascular disease was detected in 11.4%, with CAD (7.9%) being the most common diagnosis. High FRS (>20%) was seen in 8.5% of the study population. Ten athletes were diagnosed with significant CAD; 90% were asymptomatic. A high FRS was most indicative of underlying CAD (PPV 38.2%).ConclusionMasters athletes are not immune to elevated cardiovascular risk and cardiovascular disease. Comprehensive preparticipation screening including an ECG and FRS can detect cardiovascular disease. An exercise stress test should be considered in those with risk factors, regardless of fitness level.
How do trainee doctors introduce themselves to patients?
Authors: Salman Marwa , Tingas Artemis , Yentis Steve M 
Published: August 2018

AbstractObjectivesTo identify how trainee doctors introduce themselves to patients.DesignSurvey.SettingChelsea and Westminster Hospital, London.ParticipantsOne hundred trainee doctors, of mixed grades and specialties.Main outcome measuresIntroducing oneself by name, using their professional title ‘Dr’, use of the term ‘trainee’.ResultsAll 100 participants introduced themselves by name to patients, with 63% using only their first name, 18% using only their last name and 18% using a combination of both. 67% mentioned their specialty and 18% mentioned their training grade. 85% identified themselves as a doctor, but only 22% used their professional title (Dr), and only 6% introduced themselves by name, grade, specialty and title. 80% varied the way they introduced themselves to patients, depending on several factors including the clinical situation and patients’ characteristics/features. 56% said that they had changed the way they introduced themselves over time, and 42% deliberately avoided the term ‘trainee’ during introductions. There was no association between trainees’ age, gender or specialty and their comfort in describing themselves as ‘trainees’, but the more junior trainees were more comfortable using this term than the senior grades (p&lt;0.0001). Overall, 76% disliked the term ‘trainee’, for various reasons.ConclusionAll doctors in this study introduced themselves by name but the majority did not specify their training grade or trainee status, predominantly because they believed it could trigger anxiety around their competence or undermine confidence in their abilities.
High-fat diet overfeeding promotes nondetrimental liver steatosis in female mice
Authors: Arisqueta Lino , Navarro-Imaz Hiart , Labiano Ibone , Rueda Yuri , Fresnedo Olatz 
Published: August 2018

High-fat diet (HFD) feeding or leptin-deficient mice are extensively used as models resembling features of human nonalcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild-type (WT) and ob/ ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia. Given that most published works have been done in male models, we used female mice with the aim of increasing the body of evidence regarding NAFLD in female subjects. HFD promoted liver lipid accumulation only in the hyperphagic strain. Nevertheless, a decrease of lipid droplet-associated cholesteryl ester (CE) in both WT and obese animals was observed. These changes were accompanied by an improvement in the profile of lipoproteins that transport cholesterol and liver function markers in plasma from ob/ ob mice and a lower hepatic index. Using primary hepatocytes from female mice, overaccumulation of CE induced by 0.4 mM oleic acid reversed in the presence of a specific Takeda G protein-coupled bile acid receptor agonist. Nevertheless, hepatocytes from male mice were not responsive. This study suggests that enterohepatic circulation of bile acids might be one of the factors that can affect sex dimorphism in NAFLD development, which underlines the importance of including female models in the NAFLD research field.NEW & NOTEWORTHY This work provides new insight into the use of high-fat diet as a model to induce nonalcoholic fatty liver disease in wild-type and ob/ ob female mice. We show that high-fat diet induces steatosis only in ob/ ob mice while, surprisingly, several health indicators improve. Noteworthy, experiments with primary hepatocytes from male and female mice show that they express Takeda G protein-coupled bile acid receptor and that it and bile acid enterohepatic circulation might be accountable for sex dimorphism in nonalcoholic fatty liver disease development.
Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis
Authors: Määttänen Pekka , Lurz Eberhard , Botts Steven R. , Wu Richard Y. , Yeung C. William , Li Bo , Abiff Sumayyah , Johnson-Henry Kathene C. , Lepp Dion , Power Krista A. , Pierro Agostino , Surette Marc E. , Sherman Philip M. 
Published: August 2018

Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet. After weaning, C57BL/6 mice ( n = 8–15/treatment) were fed ground flaxseed (7 g/100 g diet) with either HF (HF Flx) or RF (RF Flx) diets for 4 wk before infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids, and cecal short-chain fatty acids were compared over a 14-day infection period. The RF diet protected against C. rodentium-induced colitis, whereas the RF Flx diet increased pathogen burden, exacerbated gut inflammation, and promoted gut dysbiosis. When compared with the RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although an RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation. NEW & NOTEWORTHY Our results demonstrate a strong protective effect of a reduced-fat diet against intestinal inflammation, dysbiosis, and pathogen burden during Citrobacter rodentium-induced colitis. However, ground flaxseed supplementation in the setting of a reduced-fat diet exacerbated colitis despite higher levels of intestinal n-3 polyunsaturated fatty acids and cecal short-chain fatty acids.
Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease
Authors: Meneses Annelise L. , Nam Michael C. Y. , Bailey Tom G. , Magee Rebecca , Golledge Jonathan , Hellsten Ylva , Keske Michelle A. , Greaves Kim , Askew Christopher D. 
Published: August 2018

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise. NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.
Cardiac myocyte proliferation and maturation near term is inhibited by early gestation maternal testosterone exposure
Authors: Jonker Sonnet S. , Louey Samantha , Roselli Charles E. 
Published: August 2018

Polycystic ovary syndrome is a complex and common disorder in women, and those affected experience an increased burden of cardiovascular disease. It is an intergenerational syndrome, as affected women with high androgen levels during pregnancy “program” fetal development, leading to a similar phenotype in their female offspring. The effect of excess maternal testosterone exposure on fetal cardiomyocyte growth and maturation is unknown. Pregnant ewes received biweekly injections of vehicle (control) or 100 mg testosterone propionate between 30 and 59 days of gestation (early T) or between 60 and 90 days of gestation (late T). Fetuses were delivered at ~135 days of gestation, and their hearts were enzymatically dissociated to measure cardiomyocyte growth (dimensional measurements), maturation (proportion binucleate), and proliferation (nuclear Ki-67 protein). Early T depressed serum insulin-like growth factor 1 and caused intrauterine growth restriction (IUGR; P < 0.0005). Hearts were smaller with early T ( P < 0.001) due to reduced cardiac myocyte maturation ( P < 0.0005) and proliferation ( P = 0.017). Maturation was also lower in male than female fetuses ( P = 0.004) independent of treatment. Late T did not affect cardiac growth. Early excess maternal testosterone exposure depresses circulating insulin-like growth factor 1 near term and causes IUGR in both female and male offspring. These fetuses have small, immature hearts with reduced proliferation, which may reduce cardiac myocyte endowment and predispose to adverse cardiac growth in postnatal life. While excess maternal testosterone exposure leads to polycystic ovary syndrome and cardiovascular disease in female offspring, it may also predispose to complications of IUGR and cardiovascular disease in male offspring. NEW & NOTEWORTHY Using measurements of cardiac myocyte growth and maturation in an ovine model of polycystic ovary syndrome, this study demonstrates that early gestation excess maternal testosterone exposure reduces near-term cardiomyocyte proliferation and maturation in intrauterine growth-restricted female and male fetuses. The effect of testosterone is restricted to exposure during a specific period early in pregnancy, and the effects appear mediated through reduced insulin-like growth factor 1 signaling. Furthermore, male fetuses, regardless of treatment, had fewer mature cardiomyocytes than female fetuses.
A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
Authors: Enblad Gunilla , Karlsson Hannah , Gammelgård Gustav , Wenthe Jessica , Lövgren Tanja , Amini Rose Marie , Wikstrom Kristina I. , Essand Magnus , Savoldo Barbara , Hallböök Helene , Höglund Martin , Dotti Gianpietro , Brenner Malcolm K. , Hagberg Hans , Loskog Angelica 
Published: August 2018

Abstract

Purpose:
The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19+ B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

Patients and Methods:
Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

Results:
Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14+CD33+HLA−DR−) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

Conclusions:
Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.
Noninvasive Detection of ctDNA Reveals Intratumor Heterogeneity and Is Associated with Tumor Burden in Gastrointestinal Stromal Tumor
Authors: Namløs Heidi M. , Boye Kjetil , Mishkin Skyler J. , Barøy Tale , Lorenz Susanne , Bjerkehagen Bodil , Stratford Eva W. , Munthe Else , Kudlow Brian A. , Myklebost Ola , Meza-Zepeda Leonardo A. 
Published: August 2018

Abstract
Molecular analysis of circulating tumor DNA (ctDNA) has a large potential for clinical application by capturing tumor-specific aberrations through noninvasive sampling. In gastrointestinal stromal tumor (GIST), analysis of KIT and PDGFRA mutations is important for therapeutic decisions, but the invasiveness of traditional biopsies limits the possibilities for repeated sampling. Using targeted next-generation sequencing, we have analyzed circulating cell-free DNA from 50 GIST patients. Tumor-specific mutations were detected in 16 of 44 plasma samples (36%) from treatment-naïve patients and in three of six (50%) patients treated with tyrosine kinase inhibitors. A significant association between detection of ctDNA and the modified National Institutes of Health risk classification was found. All patients with metastatic disease had detectable ctDNA, and tumor burden was the most important detection determinant. Median tumor size was 13.4 cm for patients with detectable mutation in plasma compared with 4.4 cm in patients without detectable mutation (P = 0.006). ctDNA analysis of a patient with disease progression on imatinib revealed that multiple resistance mutations were synchronously present, and detailed analysis of tumor tissue showed that these were spatially distributed in the primary tumor. Plasma samples taken throughout the course of treatment demonstrated that clonal evolution can be monitored over time. In conclusion, we have shown that detection of GIST-specific mutations in plasma is particularly feasible for patients with high tumor burden. In such cases, we have demonstrated that mutational analysis by use of liquid biopsies can capture the molecular heterogeneity of the whole tumor, and may guide treatment decisions during progression. Mol Cancer Ther; 17(11); 2473–80. ©2018 AACR.
Constitutional Patriotism, Moral Sentiment, and International Human Rights
Authors: Krause Sharon R. 
Published: August 2018

Abstract
This essay explores resources for motivating allegiance to international human rights, drawing in particular on the work of Jürgen Habermas and David Hume. It examines the ideal of constitutional patriotism as developed by Habermas and identifies limitations of that ideal in the international context. Hume’s concept of moral sentiment is then examined, specifically its ability to generate an impartial but affectively engaged moral standpoint with the power to motivate action, potentially with a wider reach than that of constitutional patriotism. Finally, the paper shows how a contemporary Hume-inspired form of moral sentiment might interact with and support the deliberative practices through which international human rights are interpreted and applied in practice. It concludes with remarks on the reciprocal relationship between moral sentiment and constitutional patriotism in the realm of human rights.