bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global longitudinal strain, myocardial storage and hypertrophy in Fabry disease
Authors: Vijapurapu Ravi , Nordin Sabrina , Baig Shanat , Liu Boyang , Rosmini Stefania , Augusto Joao , Tchan Michel , Hughes Derralynn A , Geberhiwot Tarekegn , Moon James C , Steeds Richard Paul , Kozor Rebecca 
Published: October 2018

IntroductionDetecting early cardiac involvement in Fabry disease (FD) is important because therapy may alter disease progression. Cardiovascular magnetic resonance (CMR) can detect T1 lowering, representing myocardial sphingolipid storage. In many diseases, early mechanical dysfunction may be detected by abnormal global longitudinal strain (GLS). We explored the relationship of early mechanical dysfunction and sphingolipid deposition in FD.MethodsAn observational study of 221 FD and 77 healthy volunteers (HVs) who underwent CMR (LV volumes, mass, native T1, GLS, late gadolinium enhancement), ECG and blood biomarkers, as part of the prospective multicentre Fabry400 study.ResultsAll FD had normal LV ejection fraction (EF 73%±8%). Mean indexed LV mass (LVMi) was 89±39 g/m2 in FD and 55.6±10 g/m2 in HV. 102 (46%) FD participants had left ventricular hypertrophy (LVH). There was a negative correlation between GLS and native T1 in FD patients (r=−0.515, p<0.001). In FD patients without LVH (early disease), as native T1 reduced there was impairment in GLS (r=−0.285, p<0.002). In the total FD cohort, ECG abnormalities were associated with a significant impairment in GLS compared with those without ECG abnormalities (abnormal: −16.7±3.5 vs normal: −20.2±2.4, p<0.001).ConclusionsGLS in FD correlates with an increase in LVMi, storage and the presence of ECG abnormalities. In LVH-negative FD (early disease), impairment in GLS is associated with a reduction in native T1, suggesting that mechanical dysfunction occurs before evidence of sphingolipid deposition (low T1).Trial registration numberNCT03199001; Results.
Somatic Mutations and Immune Alternation in Rectal Cancer Following Neoadjuvant Chemoradiotherapy
Authors: Ji Dengbo , Yi Haizhao , Zhang Dakui , Zhan Tiancheng , Li Zhaowei , Li Ming , Jia Jinying , Qiao Meng , Xia Jinhong , Zhai Zhiwei , Song Can , Gu Jin 
Published: October 2018

Abstract
Checkpoint blockade therapy triggers tumor-specific immune responses in a variety of cancer types. We presumed that rectal cancer patients could have become sensitive to immunotherapy after receiving neoadjuvant chemoradiotherapy (nCRT). In this study, we report immune alternation in post-nCRT patients compared with pretreatment conditions from gene-expression omnibus (GEO) data. Whole-exome sequencing of 14 locally advanced rectal cancer (LARC) patient samples showed that nCRT induced new mutations compared with the paired pretreatment biopsies, evidenced by appearance of a neoantigen landscape. An association was identified between mutation burden and enrichment of immune activation–related pathways. Animal experiment results further demonstrated that radiotherapy enhanced the efficacy of anti–PD-1. Mutation burden and the neoantigens of LARC patients were associated with response to nCRT. The mRNA expression profiling of 66 pretreatment biopsy samples from LARC patients showed that immune activation–related pathways were enriched in response to nCRT. PD-L1 expression was negatively correlated with disease-free survival in the CD8-low expression patient group who received nCRT in a cohort of 296 samples. Thus, nCRT was able to alter immune function in LARC patients, which may be associated with the appearance of neoantigens. Neoantigens could make rectal cancer patients potential candidates to receive checkpoint blockade immunotherapy, and mutation burden could be a useful biomarker to stratify patients into responding and nonresponding groups for immunotherapy. Cancer Immunol Res; 6(11); 1401–16. ©2018 AACR.
Porphyrin‐Based SOD Mimic MnTnBuOE‐2‐PyP
5+
Inhibits Mechanisms of Aortic Valve Remodeling in Human and Murine Models of Aortic Valve Sclerosis
Authors: Anselmo Wanda , Branchetti Emanuela , Grau Juan B. , Li Gen , Ayoub Salma , Lai Eric K. , Rioux Nancy , Tovmasyan Artak , Fortier Jacqueline H. , Sacks Michael S. , Batinic‐Haberle Ines , Hazen Stanley L. , Levy Robert J. , Ferrari Giovanni 
Published: October 2018

Background

Aortic valve sclerosis (
AVS
c), the early asymptomatic presentation of calcific aortic valve (AV) disease, affects 25% to 30% of patients aged >65 years. In vitro and ex vivo experiments with antioxidant strategies and antagonists of osteogenic differentiation revealed that
AVS
c is reversible. In this study, we characterized the underlying changes in the extracellular matrix architecture and valve interstitial cell activation in AVSc and tested in vitro and in vivo the activity of a clinically approved SOD (superoxide dismutase) mimic and redox‐active drug MnTnBu
OE
‐2‐PyP
5+
(
BMX
‐001).

Methods and Results

After receiving informed consent, samples from patients with
AVS
c, AV stenosis, and controls were collected. Uniaxial mechanical stimulation and in vitro studies on human valve interstitial cells were performed. An angiotensin
II
chronic infusion model was used to impose
AV
thickening and remodeling. We characterized extracellular matrix structures by small‐angle light scattering, scanning electron microscopy, histology, and mass spectrometry. Diseased human valves showed altered collagen fiber alignment and ultrastructural changes in
AVS
c, accumulation of oxidized cross‐linking products in AV stenosis, and reversible expression of extracellular matrix regulators ex vivo. We demonstrated that MnTnBu
OE
‐2‐PyP
5+
inhibits human valve interstitial cell activation and extracellular matrix remodeling in a murine model (C57
BL
/6J) of
AVS
c by electron microscopy and histology.

Conclusions

AVS
c is associated with architectural remodeling despite marginal effects on the mechanical properties in both human and mice. MnTnBu
OE
‐2‐PyP
5+
controls
AV
thickening in a murine model of
AVS
c. Because this compound has been approved recently for clinical use, this work could shift the focus for the treatment of calcific AV disease, moving from AV stenosis to an earlier presentation (
AVS
c) that could be more responsive to medical therapies.
Long‐Term Cardiac Function After Peripartum Cardiomyopathy and Preeclampsia: A Danish Nationwide, Clinical Follow‐Up Study Using Maximal Exercise Testing and Cardiac Magnetic Resonance Imaging
Authors: Ersbøll Anne S. , Bojer Annemie S. , Hauge Maria G. , Johansen Marianne , Damm Peter , Gustafsson Finn , Vejlstrup Niels G. 
Published: October 2018

Background

Long‐term clinical studies of peripartum cardiomyopathy (
PPCM
) are few. We aimed to measure the long‐term effect of
PPCM
on cardiac function in comparison with the long‐term effects of severe preeclampsia and uncomplicated pregnancy.

Methods and Results

A nationwide Danish cohort of women diagnosed with
PPCM
from 2005 to 2014 (
PPCM
group) were invited to participate in a clinical follow‐up study including maximal cardiopulmonary exercise testing and cardiac magnetic resonance imaging. Matched women with previous severe preeclampsia (preeclampsia group) and previous uncomplicated pregnancies (uncomplicated pregnancies group) served as comparison groups. A total of 84 women with 28 in each group participated. Median time to follow‐up after
PPCM
was 91 months. Most women (85%) in the
PPCM
group reported no symptoms of heart failure. Mean left ventricular ejection fraction in the
PPCM
group was normal at 62%, but significantly lower than in the preeclampsia group and the uncomplicated pregnancies group where mean left ventricular ejection fraction was 69% and 67%, respectively (
P
<0.0001). Women in the
PPCM
group also had impaired diastolic function with reduced left ventricular peak filling rate, left atrial passive emptying volume, and left atrial passive emptying fraction. Maximal exercise capacity (peak
VO
2
) was also reduced in the
PPCM
group compared with the preeclampsia group and the uncomplicated pregnancies group, and
PPCM
, high body mass index, and low left ventricular ejection fraction independently predicted reduced peak
VO
2
. Only 1 woman with
PPCM
had late gadolinium enhancement.

Conclusions

Women generally recovered left ventricular ejection fraction and were asymptomatic 7 years after
PPCM
, but had subtle diastolic dysfunction on cardiac magnetic resonance imaging and reduced peak
VO
2
. Focal myocardial fibrosis assessed with late gadolinium enhancement was, however, uncommon.
Ischemic Heart Disease Modifies the Association of Atrial Fibrillation With Mortality in Heart Failure With Reduced Ejection Fraction
Authors: Mercer Ben N. , Koshy Aaron , Drozd Michael , Walker Andrew M. N. , Patel Peysh A. , Kearney Lorraine , Gierula John , Paton Maria F. , Lowry Judith E. , Kearney Mark T. , Cubbon Richard M. , Witte Klaus K. 
Published: October 2018

Background

The
CASTLE
‐
AF
(Catheter Ablation versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation) trial recently reported that catheter ablation of atrial fibrillation (
AF
) improves survival in heart failure (HF) with reduced ejection fraction (
HF
r
EF
). However, established
AF
was not associated with mortality in trials of contemporary
HF
r
EF
pharmacotherapies. We investigated whether
HF
r
EF
pathogenesis may influence the conclusions of studies evaluating the prognostic impact of
AF
.

Methods and Results

Using a prospective cohort study of 791 patients with HFr
EF
, with
AF
determined using 24‐hour ambulatory
ECG
monitoring, univariable and multivariable Cox regression analyses were used to define the association between
AF
and mode‐specific mortality (mean follow‐up of 5.4 years). One‐year HF‐related hospitalization was assessed with binary logistic regression analysis. One‐year cardiac remodeling was assessed in a subgroup (n=378) using echocardiography.
AF
was present in 28.2% of patients, with 9.4% of these being paroxysmal. While
AF
was associated with increased risk of all‐cause mortality (hazard ratio, 1.27; 95% confidence interval 1.03–1.57), with diverging survival curves after 1 year of follow‐up, this association was lost in age‐sex–adjusted analyses. However,
AF
was associated with increased risk of age‐sex–adjusted all‐cause mortality in people with ischemic pathogenesis, with a statistically significant interaction between pathogenesis and
AF.
This was predominantly attributed to progressive HF deaths. After 1 year, HF hospitalization and cardiac remodeling were not associated with
AF
, even in people with ischemic pathogenesis.

Conclusions

AF
is associated with increased risk of death in
HF
r
EF
of ischemic pathogenesis, predominantly due to progressive HF deaths during long‐term follow‐up.
HF
r
EF
pathogenesis should be considered in trial design and interpretation.
Predictive Value of
18
F‐Sodium Fluoride Positron Emission Tomography in Detecting High‐Risk Coronary Artery Disease in Combination With Computed Tomography
Authors: Kitagawa Toshiro , Yamamoto Hideya , Nakamoto Yumiko , Sasaki Ko , Toshimitsu Shinya , Tatsugami Fuminari , Awai Kazuo , Hirokawa Yutaka , Kihara Yasuki 
Published: October 2018

Background

Application of
18
F‐sodium fluoride (
18
F‐NaF) positron emission tomography (
PET
) to coronary artery disease has attracted interest. We investigated the utility of
18
F‐NaF uptake for predicting coronary events and evaluated the combined use of coronary computed tomography (CT) angiography (
CCTA
) and
18
F‐NaF
PET
/CT in
coronary artery disease
risk assessment.

Methods and Results

This study included patients with ≥1 coronary atherosclerotic lesion detected on
CCTA
who underwent
18
F‐NaF
PET
/
CT
. High‐risk plaque on
CCTA
was defined as plaque with low density (<30 Hounsfield units) and high remodeling index (>1.1). Focal
18
F‐NaF uptake in each lesion was quantified using the maximum tissue:background ratio (
TBR
max
), and maximum
TBR
max
per patient (M‐
TBR
max
) was determined. Thirty‐two patients having a total of 112 analyzed lesions were followed for 2 years after
18
F‐NaF
PET
/
CT
scan, and 11 experienced coronary events (acute coronary syndrome and/or late coronary revascularization [after 3 months]). Patients with coronary events had higher M‐
TBR
max
than those without (1.39±0.18 versus 1.19±0.17, respectively;
P
=0.0034). The optimal M‐
TBR
max
cutoff to predict coronary events was 1.28 (area under curve: 0.79). Patients with M‐
TBR
max
≥1.28 had a higher risk of earlier coronary events than those with lower M‐
TBR
max
(
P
=0.0062 by log‐rank test). In patient‐based (n=41) and lesion‐based (n=143) analyses of
CCTA
findings that predicted higher coronary
18
F‐NaF uptake, the presence of high‐risk plaque was a significant predictor of both M‐
TBR
max
≥1.28 and
TBR
max
≥1.28.

Conclusions

18
F‐NaF
PET
/
CT
has the potential to detect high‐risk
coronary artery disease
and individual coronary lesions and to predict future coronary events when combined with
CCTA
.

Clinical Trial Registration

URL
:
www.umin.ac.jp
. Unique identifier:
UMIN
000013735.
Real-world use of PCSK9 inhibitors: A single-center experience
Authors: Sarsam Sinan , Berry Abeer , Degheim George , Singh Robby , Zughaib Marcel 
Published: October 2018

Objective Hyperlipidemia is an important risk factor for atherosclerotic cardiovascular disease. Many patients are intolerant to or have limited benefit from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved for treating hyperlipidemia in these patients. We sought to investigate the impact of these medications in a real-world cardiology practice. Methods This was a retrospective study of 17 patients with either heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) levels above the treatment target despite maximally tolerated statins. Baseline lipid profile was compared with a repeat lipid profile obtained 4 to 6 weeks after initiating treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor treatment was 10.7 months. Lipid profile comparison showed that total cholesterol decreased from 243 ± 72 to 148 ± 39 (mg/dL) (39% reduction), triglycerides decreased from 185 ± 86 to 149 ± 62 (mg/dL) (19.5% reduction), high-density lipoprotein cholesterol increased from 56 ± 20 to 62 ± 26 (mg/dL) (10.7% increase), and LDL-C decreased from 154 ± 30 to 57 ± 32 (mg/dL) (63% reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.
Co-occurrence of acute ophthalmoplegia (without ataxia) and idiopathic intracranial hypertension
Authors: Yeak Justin , Zahari Mimiwati , Singh Sujaya , Mohamad Nor Fadhilah 
Published: October 2018

Background: Acute ophthalmoparesis without ataxia was designated as ‘atypical Miller Fisher syndrome’ as it presents with progressive, relatively symmetrical ophthalmoplegia, but without ataxia nor limb weakness, in the presence of anti-GQ1b antibody. Idiopathic intracranial hypertension is characterized by signs of raised intracranial pressure occurring in the absence of cerebral pathology, with normal composition of cerebrospinal fluid and a raised opening pressure of more than 20 cmH2O during lumbar puncture. We aim to report a rare case of acute ophthalmoplegia with co-occurrence of raised intracranial pressure. Case Description: A 28-year-old gentleman with body mass index of 34.3 was referred to us for management of double vision of 2 weeks duration. His symptom started after a brief episode of upper respiratory tract infection. His best corrected visual acuity was 6/6 OU. He had bilateral sixth nerve palsy worse on the left eye and bilateral hypometric saccade. His deep tendon reflexes were found to be hyporeflexic in all four limbs. No sensory or motor power deficit was detected, and his gait was normal. Plantar reflexes were downwards bilaterally and cerebellar examination was normal. Both optic discs developed hyperaemia and swelling. Magnetic resonance imaging of brain was normal and lumbar puncture revealed an opening pressure of 50 cmH2O. Anti-GQ1b IgG and anti-GT1a IgG antibody were tested positive. Conclusion: Acute ophthalmoparesis without ataxia can present with co-occurrence of raised intracranial pressure. It is important to have a full fundoscopic assessment to look for papilloedema in patients presenting with Miller Fisher syndrome or acute ophthalmoparesis without ataxia.
Effect of Exercise on Behavioral Symptoms and Pain in Patients With Dementia Living in Nursing Homes
Authors: Maltais Mathieu , Rolland Yves , Vellas Bruno , Haÿ Paul-Emile , Armaingaud Didier , Cestac Philippe , Rouch Laure , Cesari Matteo , de Souto Barreto Philipe 
Published: October 2018

Objectives: Examine the effects of a 6-month exercise intervention on neuropsychiatric symptoms, pain, and medication consumption in older people with dementia (PWD) living in nursing homes (NH). Methods: Ninety-one older PWD living in NH performed a 6-month structured exercise intervention (n = 44) or a social activity intervention (n = 47). Neuropsychiatric symptoms were measured by the neuropsychiatric inventory (NPI), pain was assessed using the Algoplus scale, and dementia-related drug prescriptions were obtained for all participants. Results: Between-group analysis found a nonsignificant difference that could be of clinical relevance: a 4-point difference in the NPI and 1.3-point difference in the reduction of the number of medications favoring exercisers. No significant differences were found for pain, and a trend was found for an increase in medication consumption in the social group. Conclusion: Exercise effects did not differ from social intervention effects on neuropsychiatric symptoms, pain, and medication consumption in older PWD living in NH.
Netnographic Slog
Authors: Wallace Ruth , Costello Leesa , Devine Amanda 
Published: October 2018

Active, participatory netnography, in contrast to passive netnography, is essential if researchers are to gain rich rewards from the rigorous collection of qualitative data. However, researchers should be aware of the ‘netnographic slog’; “the blood, sweat and tears” associated with eliciting quality data and encouraging active participation in online communities. This article examines the – Supporting Nutrition for Australian Childcare (SNAC) – online community of practice, established to support healthy eating practices in early childhood education and care settings. To ensure research rigour, Kozinets’ netnographic steps were employed. Garnering member participation in this online community was a slog; most community content was contributed by few members, although accessed by many. The success (and failure) of the creative elicitation strategies implemented by the researchers to promote participation are discussed, and examples provided that could be used by other netnographers in online communities. A key consideration, however, appears to be the waning success of web-based discussion boards as an effective platform. Future netnographers should carefully consider the effort required to attract new community members and encourage participation. While SNAC is a unique resource, presenting an ideal platform to launch further initiatives, other more effective social media platforms that can support healthy eating in this key setting should be considered. If participatory netnography is to be successful, budding netnographers must be prepared to invest the blood, sweat and tears required to nurture emerging communities of practice.
Folk theorizing the quality and credibility of health apps
Authors: Kanthawala Shaheen , Joo Eunsin , Kononova Anastasia , Peng Wei , Cotten Shelia 
Published: October 2018

Increase in availability and accessibility of health apps raises important questions regarding strategies smartphone owners use to determine what health apps to download. As mobile health apps aim at helping users manage their healthy lifestyles and health conditions, it is important for researchers, developers, and educators to know how individuals find and assess the quality and credibility of these apps, and what guides their decisions to download and use them. We conducted semistructured interviews using the think-aloud technique with 19 community members in a U.S. Midwestern city and analyzed the data using open coding thematic analysis to determine how smartphone users assess health apps before downloading them. We find users determined app credibility through quick, but holistic cues based on the app’s features, and “borrowed” credibility decisions from friends or other health app users. App quality was often equated to personal preferences, that is, how the app met those preferences. Additional cues (cost, app size, order in App Store) led to download decisions but had nothing to do with quality or credibility. We categorized the findings as folk theories regarding quality and credibility of health apps and discuss them using information dual-processing models and media and technology literacy.
Mentoring for urologists
Authors: Terry Tim , Redfern Nancy , French Gordon 
Published: October 2018

Trainee and established urologists are familiar with ‘generic mentoring’ as a potpourri of helping aids that include supervision, coaching, buddying, career advice, counselling and patronage to enable mentees to develop professionally. However, most are unfamiliar with ‘developmental mentoring’ as a highly specific learnt technique through which mentors help mentees, by interactive dialogue, to choose their own agendas and arrive at their own solutions to career/professional/personal opportunities or difficulties as distinct from the paternalistic mentor approach typified by the downward flow of information generated by ‘generic mentoring’. This paper is a systematic review of developmental mentoring as pertains to urologists in the UK, and reports outcomes of 1-hour taster sessions between Egan-trained mentors and urologists offered at British Association of Urological Surgeons (BAUS) annual general meetings since 2013. Both the General Medical Council and the Royal College of Surgeons of England imply that ‘mentoring’ is mandatory for both trainees and trained urologists, but fail to clarify what they mean by a ‘mentor’, which potentially creates a void in providing ‘developmental mentoring’ since the later requires specific training and is costly to provide. Currently, most ‘developmental mentoring’ is performed by trained staff in Local Education and Training Boards or National Health Service Trusts. BAUS has an opportunity to offer ‘developmental mentoring’ through a portal on its website to manage opportunities and difficulties experienced by its members. Level of evidence: This paper is a systematic review as pertains to the place of mentoring in current urological practice. By its nature, it has reviewed previous narrative reviews and its highest level of evidence is a contemporary paper from 2016, which was a comparative cross-sectional study; other case series were reviewed. Overall, this amounts to level 4 with a recommendation of C as per the Oxford Centre for Evidence-based Medicine Levels of Evidence.