bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological processes of suffering of palliative care patients in Malaysia: a thematic analysis
Authors: Tan Seng Beng , Loh Ee Chin , Lam Chee Loong , Ng Chong Guan , Lim Ee Jane , Boey Christopher Chiong Meng 
Published: February 2019

Although suffering in palliative care has received increasing attention over the past decade, the psychological processes that underpin suffering remain relatively unexplored.ObjectiveTo understand the psychological processes involved in the experiencing of suffering at the end phase of life.MethodsSemistructured interviews were conducted with 20 palliative care inpatients from an academic medical centre in Kuala Lumpur, Malaysia. The transcripts were thematically analysed with NVIVO9.Results5 themes of psychological processes of suffering were generated: (1) perceptions, (2) cognitive appraisals, (3) hope and the struggles with acceptance, (4) emotions and (5) clinging. A model of suffering formation was constructed.ConclusionThe findings may inform the development of mechanism-based interventions in the palliation of suffering.
Impact of instructor professional background and interim retesting on knowledge and self-confidence of schoolchildren after basic life support training: a cluster randomised longitudinal study
Authors: Haseneder Rainer , Skrzypczak Matthias , Haller Bernhard , Beckers Stefan K , Holch Julia , Wank Christina , Kochs Eberhard , Schulz Christian M 
Published: February 2019

IntroductionTo increase the rate of bystander resuscitation, basic life support (BLS) training for schoolchildren is now recommended on a broad level. However, debate continues about the optimal teaching methods. In this study, we investigated the effects of a 90 min BLS training on female pupils’ BLS knowledge and self-confidence and whether learning outcomes were influenced by the instructors’ professional backgrounds or test-enhanced learning.MethodsWe conducted a cluster randomised, longitudinal trial in a girls’ grammar school in Germany from 2013 to 2014. Pupils aged 10–17 years were randomised to receive BLS training conducted by either emergency physicians or medical students. Using a multiple-choice questionnaire and a Likert-type scale, BLS knowledge and self-confidence were investigated before training (t0), 1 week (t1) and 9 months after training (t2). To investigate whether test-enhanced learning influenced learning outcomes, the questionnaire was administered 6 months after the training in half of the classrooms. The data were analysed using linear mixed-effects models.ResultsThe study included 460 schoolchildren. BLS knowledge (mean number of correct answers) increased from 5.86 at t0to 9.24 at t1(p<0.001) and self-confidence (mean score on the Likert-type scale) increased from 8.70 at t0to 11.29 at t1(p<0.001). After 9 months, knowledge retention was good (8.94 at t2; p=0.080 vs t1), but self-confidence significantly declined from t1to 9.73 at t2(p<0.001). Pupils trained by medical students showed a slight but statistically significant greater increase in the knowledge at both t1and t2, whereas instructors’ background did not influence gain or retention of self-confidence. Retesting resulted in a marginally, non-significantly better retention of knowledge.ConclusionsBLS training led to short-term gains in knowledge and self-confidence. Although knowledge was retained at 9 months after the training session, self-confidence significantly decreased. Interim testing did not appear to impact retention of knowledge or self-confidence. Medical students should be considered as instructors for these courses given their favourable learning outcomes and greater availability.
Evaluation of the efficacy and safety of sarilumab combination therapy in patients with rheumatoid arthritis with inadequate response to conventional disease-modifying antirheumatic drugs or tumour necrosis factor α inhibitors: systematic literature review and network meta-analyses
Authors: Choy Ernest , Freemantle Nick , Proudfoot Clare , Chen Chieh-I , Pollissard Laurence , Kuznik Andreas , Van Hoogstraten Hubert , Mangan Erin , Carita Paulo , Huynh Thi-Minh-Thao 
Published: February 2019

ObjectiveTo compare efficacy and safety of subcutaneous sarilumab 200 mg and 150 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARDs) versus other targeted DMARDs+csDMARDs and placebo+csDMARDs, in inadequate responders to csDMARDs (csDMARD-IR) or tumour necrosis factor α inhibitors (TNFi-IR).MethodsSystematic literature review and network meta-analyses (NMA) conducted on 24 week efficacy and safety outcomes: Health Assessment Questionnaire Disability Index, modified total sharp score (mTSS, including 52 weeks), American College of Rheumatology (ACR) 20/50/70, European League Against Rheumatism Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28)<2.6; serious infections/serious adverse events (including 52 weeks).Results53 trials were selected for NMA.csDMARD-IR: Sarilumab 200 mg+csDMARDs and 150 mg+csDMARDs were superior versus placebo+csDMARDs on all outcomes. Against most targeted DMARDs, sarilumab 200 mg showed no statistically significant differences, except superiority to baricitinib 2 mg, tofacitinib and certolizumab on 24 week mTSS. Sarilumab 150 mg was similar to all targeted DMARDs.TNFi-IR:Sarilumab 200 mg was similar to abatacept, golimumab, tocilizumab 4 mg and 8 mg/kg intravenously and rituximab on ACR20/50/70, superior to baricitinib 2 mg on ACR50 and DAS28<2.6 and to abatacept, golimumab, tocilizumab 4 mg/kg intravenously and rituximab on DAS28<2.6. Sarilumab 150 mg was similar to targeted DMARDs but superior to baricitinib 2 mg and rituximab on DAS28<2.6 and inferior to tocilizumab 8 mg on ACR20 and DAS28<2.6. Serious adverse events, including serious infections, appeared similar for sarilumab versus comparators.ConclusionsResults suggest that in csDMARD-IR and TNFi-IR (a smaller network), sarilumab+csDMARD had superior efficacy and similar safety versus placebo+csDMARDs and at least similar efficacy and safety versus other targeted DMARDs+csDMARDs.
In-Depth Analysis on Microarchitectures of Modern Heterogeneous CPU-FPGA Platforms
Authors: Choi Young-Kyu , Cong Jason , Fang Zhenman , Hao Yuchen , Reinman Glenn , Wei Peng 
Published: February 2019

Conventional homogeneous multicore processors are not able to provide the continued performance and energy improvement that we have expected from past endeavors. Heterogeneous architectures that feature specialized hardware accelerators are widely considered a promising paradigm for resolving this issue. Among different heterogeneous devices, FPGAs that can be reconfigured to accelerate a broad class of applications with orders-of-magnitude performance/watt gains, are attracting increased attention from both academia and industry. As a consequence, a variety of CPU-FPGA acceleration platforms with diversified microarchitectural features have been supplied by industry vendors. Such diversity, however, poses a serious challenge to application developers in selecting the appropriate platform for a specific application or application domain.
This article aims to address this challenge by determining which microarchitectural characteristics affect performance, and in what ways. Specifically, we conduct a quantitative comparison and an in-depth analysis on five state-of-the-art CPU-FPGA acceleration platforms: (1) the Alpha Data board and (2) the Amazon F1 instance that represent the traditional PCIe-based platform with private device memory; (3) the IBM CAPI that represents the PCIe-based system with coherent shared memory; (4) the first generation of the Intel Xeon+FPGA Accelerator Platform that represents the QPI-based system with coherent shared memory; and (5) the second generation of the Intel Xeon+FPGA Accelerator Platform that represents a hybrid PCIe-based (non-coherent) and QPI-based (coherent) system with shared memory. Based on the analysis of their CPU-FPGA communication latency and bandwidth characteristics, we provide a series of insights for both application developers and platform designers. Furthermore, we conduct two case studies to demonstrate how these insights can be leveraged to optimize accelerator designs. The microbenchmarks used for evaluation have been released for public use.
Analysis of Mucosal Melanoma Whole-Genome Landscapes Reveals Clinically Relevant Genomic Aberrations
Authors: Zhou Rong , Shi Chaoji , Tao Wenjie , Li Jiang , Wu Jing , Han Yong , Yang Guizhu , Gu Ziyue , Xu Shengming , Wang Yujue , Wang Lizhen , Wang Yanan , Zhou Guoyu , Zhang Chenping , Zhang Zhiyuan , Sun Shuyang 
Published: February 2019

Abstract

Purpose:
Unlike advances in the genomics-driven precision treatment of cutaneous melanomas, the current poor understanding of the molecular basis of mucosal melanomas (MM) has hindered such progress for MM patients. Thus, we sought to characterize the genomic landscape of MM to identify genomic alterations with prognostic and/or therapeutic implications.

Experimental Design:
Whole-genome sequencing (WGS) was performed on 65 MM samples, including 63 paired tumor blood samples and 2 matched lymph node metastases, with a further droplet digital PCR–based validation study of an independent MM cohort (n = 80). Guided by these molecular insights, the FDA-approved CDK4/6 inhibitor palbociclib was tested in an MM patient-derived xenograft (PDX) trial.

Results:
Besides the identification of well-recognized driver mutations of BRAF (3.1%), RAS family (6.2%), NF1 (7.8%), and KIT (23.1%) in MMs, our study also found that (i) mutations and amplifications in the transmembrane nucleoporin gene POM121 (30.8%) defined a patient subgroup with higher tumor proliferation rates; (ii) enrichment of structural variations between chromosomes 5 and 12 defined a patient subgroup with significantly worse clinical outcomes; (iii) over 50% of the MM patients harbored recurrent focal amplification of several oncogenes (CDK4, MDM2, and AGAP2) at 12q13-15, and this co-occurred significantly with amplification of TERT at 5p15, which was verified in the validation cohort; (iv) the PDX trial demonstrated robust antitumor effects of palbociclib in MMs harboring CDK4 amplification.

Conclusions:
Our largest-to-date cohort WGS analysis of MMs defines the genomic landscape of this deadly cancer at unprecedented resolution and identifies genomic aberrations that could facilitate the delivery of precision cancer treatments.
See related commentary by Shoushtari, p. 3473
Radiotherapy and Cisplatin Increase Immunotherapy Efficacy by Enabling Local and Systemic Intratumoral T-cell Activity
Authors: Kroon Paula , Frijlink Elselien , Iglesias-Guimarais Victoria , Volkov Andriy , van Buuren Marit M. , Schumacher Ton N. , Verheij Marcel , Borst Jannie , Verbrugge Inge 
Published: February 2019

AbstractTo increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast cancer model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate with anti–PD-1 treatment. One requirement to improve anti-PD-1–mediated tumor control was to promote tumor-specific cytotoxic T-cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor. A second requirement was to overrule PD-1–unrelated mechanisms of CTL suppression in the tumor microenvironment (TME). This was achieved by radiotherapy and cisplatin treatment. In the context of CD137/PD-1–targeting immunotherapy, radiotherapy allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T-cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases.
Integrative Functional Annotation of 52 Genetic Loci Influencing Myocardial Mass Identifies Candidate Regulatory Variants and Target Genes
Authors: Hemerich Daiane , Pei Jiayi , Harakalova Magdalena , van Setten Jessica , Boymans Sander , Boukens Bas J. , Efimov Igor R. , Michels Michelle , van der Velden Jolanda , Vink Aryan , Cheng Caroline , van der Harst Pim , Moore Jason H. , Mokry Michal , Tragante Vinicius , Asselbergs Folkert W. 
Published: February 2019

Background:
Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context.

Methods:
We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements.

Results:

Regions differentially affected in disease showed a stronger enrichment (
P
=8.6×10
−5
) for QRS-associated variants than those not showing differential activity (
P
=0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment (
P
=0.001) than differentially acetylated enhancers (
P
=0.8) and super-enhancers (
P
=0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped.

Conclusions:
Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.
Interleukin-6 Receptor Signaling and Abdominal Aortic Aneurysm Growth Rates
Authors: Paige Ellie , Clément Marc , Lareyre Fabien , Sweeting Michael , Raffort Juliette , Grenier Céline , Finigan Alison , Harrison James , Peters James E. , Sun Benjamin B. , Butterworth Adam S. , Harrison Seamus C. , Bown Matthew J. , Lindholt Jes S. , Badger Stephen A. , Kullo Iftikhar J. , Powell Janet , Norman Paul E. , Scott D. Julian A. , Bailey Marc A. , Rose-John Stefan , Danesh John , Freitag Daniel F. , Paul Dirk S. , Mallat Ziad 
Published: February 2019

Background:

The Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor (
IL6R
) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the
IL6R
-Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection.

Methods:

Using data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the
IL6R
-Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death.

Results:

After adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13–0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was −0.06 mm per year (−0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival (
P
<0.05).

Conclusions:
Our proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.
Sex Differences in the Prevalence of, and Trends in, Cardiovascular Risk Factors, Treatment, and Control in the United States, 2001 to 2016
Authors: Peters Sanne A.E. , Muntner Paul , Woodward Mark 
Published: February 2019

Background:
Improvements have been made in the treatment and control of some but not all major cardiovascular risk factors in the United States. It remains unclear whether women and men have benefited equally.

Methods:

Data from the 2001 to 2002 through the 2015 to 2016 US National Health and Nutrition Examination Survey on adults aged 20 to 79 years were used. We assessed sex differences in temporal trends in the levels of systolic blood pressure, body mass index, smoking status, high-density lipoprotein and total cholesterol, and hemoglobin A
1c
. Trends in treatment and control rates of hypertension, diabetes mellitus, and dyslipidemia were also assessed.

Results:

Overall, 35 416 participants (51% women) were included. Trends in systolic blood pressure, smoking status, high-density lipoprotein cholesterol, and hemoglobin A
1c
were similar between the sexes. Body mass index increased more in women than men (
P
=0.006). Mean levels were 28.1 and 29.6 kg/m
2
in women and 27.9 and 29.0 kg/m
2
in men in 2001 to 2004 and 2013 to 2016, respectively. Total cholesterol decreased more in men than women (
P
=0.002): mean levels in 2001 to 2004 and 2013 to 2016, respectively, were 203 and 194 mg/dL in women and 201 and 188 mg/dL in men. Improvements in the control of hypertension, diabetes mellitus, and dyslipidemia were similar between the sexes; however, sex differences persisted. In 2013 to 2016, control rates in women versus men were 30% versus 22% for hypertension, 30% versus 20% for diabetes mellitus, and 51% versus 63% for dyslipidemia.

Conclusions:
Temporal trends in cardiovascular risk factor levels were broadly similar between the sexes, except for total cholesterol and body mass index. Sex differences in the control of hypertension, diabetes mellitus, and dyslipidemia persist, and further efforts are required to reduce this differential.
Effects of a Disease Management Program for Preventing Recurrent Ischemic Stroke
Authors: Fukuoka Yasuko , Hosomi Naohisa , Hyakuta Takeshi , Omori Toyonori , Ito Yasuhiro , Uemura Jyunichi , Yagita Yoshiki , Kimura Kazumi , Matsumoto Masayasu , Moriyama Michiko ,   for DMP Stroke Trial Investigators
Published: February 2019

Background and Purpose—
Disease management is a healthcare strategy that includes self-management education and treatment coordination. We conducted a randomized controlled trial to determine whether a disease management program intervention could improve risk factor profiles and, thus, reduce the recurrence of stroke and other cardiovascular diseases.

Methods—
This study is a prospective randomized, open-label, parallel group study involving outpatients with a history of stroke. Between September 2010 and November 2012, we enrolled patients aged between 40 and 80 years who experienced their last ischemic stroke event or transient ischemic attack within 1 year. After stratifying by the ischemic stroke subtype, 321 subjects (67.5±8.5 years, 95 female) were randomly assigned to either the disease management program intervention group (n=156) or the usual care group (n=165). The primary end point of this study was the difference in the Framingham risk score (general cardiovascular disease 10-year risk) from baseline. The secondary end points of this study included stroke recurrence, onset of cardiovascular disease, all-cause mortality, and all vascular events.

Results—
Regarding the primary end point, there was no significant difference in the changes in the Framingham risk score at any follow-up time between the groups. The incidence of stroke recurrence tended to be lower in the disease management program intervention group, although no significant difference was found (hazard ratio, 0.49; 95% CI, 0.19–1.29).

Conclusions—
We were unable to demonstrate a clear benefit of disease management program intervention.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02121327.
Prediction of Outcomes for Ruptured Aneurysm Surgery
Authors: Ban Vin Shen , El Ahmadieh Tarek Y. , Aoun Salah G. , Plitt Aaron R. , Lyon Kristopher A. , Eddleman Christopher , Beecher Jeffrey , McDougall Cameron M. , Reisch Joan , Welch Babu G. , Samson Duke , Batjer H. Hunt , White Jonathan 
Published: February 2019

Background and Purpose—
Predicting long-term functional outcomes after intracranial aneurysmal rupture can be challenging. We developed and validated a scoring system—the Southwestern Aneurysm Severity Index—that would predict functional outcomes at 1 year after clipping of ruptured aneurysms.

Methods—
Ruptured aneurysms treated microsurgically between 2000 and 2014 were included. Outcome was defined as Glasgow Outcome Score (ranging from 1, death, to 5, good recovery) at 1 year. The Southwestern Aneurysm Severity Index is composed of multiple prospectively recorded patient demographic, clinical, radiographic, and aneurysm-specific variables. Multivariable analyses were used to construct the best predictive models for patient outcomes in a random 50% of the cohort and validated in the remaining 50%. A scoring system was created using the best model.

Results—

We identified 527 eligible patients. The Glasgow Outcome Score at 1 year was 4 to 5 in 375 patients (71.2%). In the multivariable logistic regression, the best predictive model for unfavorable outcome included intracerebral hemorrhage (odds ratio [OR], 2.53; 95% CI, 1.55−4.13), aneurysmal size ≥20 mm (OR, 6.07; 95% CI, 1.92−19.2), intraventricular hemorrhage (OR, 2.56; 95% CI, 1.15−5.67), age >64 (OR, 3.53; 95% CI, 1.70−7.35), location (OR, 1.82; 95% CI, 1.10−3.03), and hydrocephalus (OR, 2.39; 95% CI, 1.07−5.35). The Southwestern Aneurysm Severity Index predicts Glasgow Outcome Score at 1 year with good discrimination (area under the receiver operating characteristic curve, derivation: 0.816, 95% CI, 0.759−0.873; validation: 0.803, 95% CI, 0.746−0.861) and accurate calibration (
R
2
=0.939).

Conclusions—
The Southwestern Aneurysm Severity Index has been internally validated to predict 1 year Glasgow Outcome Scores at initial presentation, thus optimizing patient or family counseling and possibly guiding therapeutic efforts.
Erratum: unnecessary neotypification of Psidiastrum (Myrtaceae)
Authors: MAZINE FIORELLA FERNANDA 
Published: February 2019

The only species of Psidiastrum, P. dubium Bello (1881: 272), native to Puerto Rico, is a synonym of Eugenia axillaris (Swartz 1788: 78) Willdenow (1799: 960), a Caribbean/Central American species. In our 2016 paper on sections in Eugenia Linnaeus (1753: 470), Mazine et al. 2016), a neotype was designated for P. dubium. Nevertheless, this had already been done in 2015 by Santiago-Valentín et al. (2015: 335). Therefore the neotypification presented by Mazine et al. (2016) should be disregarded. This is a minor point, but I hope it helps in future publications.