bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of physical exercise on cognitive function and brain measures after chemotherapy in patients with breast cancer (PAM study): protocol of a randomised controlled trial
Authors: Witlox Lenja , Schagen Sanne B , de Ruiter Michiel B , Geerlings Mirjam I , Peeters Petra H M , Koevoets Emmie W , van der Wall Elsken , Stuiver Martijn , Sonke Gabe , Velthuis Miranda J , Palen Job A M van der , Jobsen Jan J , May Anne M , Monninkhof E M 
Published: June 2019

IntroductionAfter treatment with chemotherapy, many patients with breast cancer experience cognitive problems. While limited interventions are available to improve cognitive functioning, physical exercise showed positive effects in healthy older adults and people with mild cognitive impairment. The Physical Activity and Memory study aims to investigate the effect of physical exercise on cognitive functioning and brain measures in chemotherapy-exposed patients with breast cancer with cognitive problems.Methods and analyticsOne hundred and eighty patients with breast cancer with cognitive problems 2–4 years after diagnosis are randomised (1:1) into an exercise intervention or a control group. The 6-month exercise intervention consists of twice a week 1-hour aerobic and strength exercises supervised by a physiotherapist and twice a week 1-hour Nordic or power walking. The control group is asked to maintain their habitual activity pattern during 6 months. The primary outcome (verbal learning) is measured at baseline and 6 months. Further measurements include online neuropsychological tests, self-reported cognitive complaints, a 3-tesla brain MRI, patient-reported outcomes (quality of life, fatigue, depression, anxiety, work performance), blood sampling and physical fitness. The MRI scans and blood sampling will be used to gain insight into underlying mechanisms. At 18 months online neuropsychological tests, self-reported cognitive complaints and patient-reported outcomes will be repeated.Ethics and disseminationStudy results may impact usual care if physical exercise improves cognitive functioning for breast cancer survivors.Trial registration numberNTR6104
‘Links2HealthierBubs’ cohort study: protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women
Authors: Sarna Mohinder , Andrews Ross , Moore Hannah , Binks Michael J , McHugh Lisa , Pereira Gavin F , Blyth Christopher C , Van Buynder Paul , Lust Karin , Effler Paul , Lambert Stephen B , Omer Saad B , Mak Donna B , Snelling Thomas , D’Antoine Heather A , McIntyre Peter , de Klerk Nicholas , Foo Damien , Regan Annette K 
Published: June 2019

IntroductionPregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes.Methods and analysis‘Links2HealthierBubs’ is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers.Ethics and disseminationEthical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women’s Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public.
Risk of hospital-treated injury in children with cerebral palsy: a population-based cohort study
Authors: Määttänen Laura , Ripatti Liisi , Rautava Päivi , Koivisto Mari , Haataja Leena 
Published: June 2019

AimTo study whether cerebral palsy (CP) increases the risk of hospital-treated injuries in children up to 13 years of age.MethodsA Finnish population-based cohort (n=328 903) of children born during 2001 to 2006 was followed up for hospital-treated injuries until the end of 2014 via linkage of nation-wide registers. The rate of first injury was compared in children with and without CP. The effect of CP type, gender, severe comorbidities (intellectual disability, epilepsy, hearing or visual impairment), and the type of injury was evaluated.ResultsChildren with CP had an increased risk of injury compared with children without CP (unadjusted HR: 1.2, 95% CI: 1.0 – 1.4, p=0.40). Girls with CP (n=191) had a higher risk of injury compared with girls without CP (29% vs 22%, HR: 1.4, 95% CI: 1.1 to 1.8, p = 0.01). Any comorbidity increased the risk of injury (HR: 1.5, 95% CI: 1.1 to 2.2, p = 0.015) among children with CP. Children with CP had a higher risk of traumatic brain injury (HR: 1.7, 95% CI 1.2 to 2.4, p = 0.002) than children without CP.ConclusionGirls with CP had the highest risk of hospital-treated injury. Children with CP are particularly prone to traumatic brain injuries.
Echocardiographic subtypes of heart failure in consecutive hospitalised patients with dyspnoea
Authors: Nielsen Olav Wendelboe , Valeur Nana , Sajadieh Ahmad , Fabricius-Bjerre Andreas , Carlsen Christian Malchau , Kober Lars 
Published: June 2019

Heart failure with preserved ejection fraction (HFpEF) involves half of hospitalised patients with heart failure (HF), but estimates vary due to unclear diagnostic criteria. We performed a prospective observational study of hospitalised patients admitted with dyspnoea. The aim was to apply contemporary guidelines to diagnose HF due to valvular disease (HFvhd), HF due to reduced ejection fraction (HFrEF), HF due to midrange EF (HFmrEF) and HFpEF in relation to presumed cardiac or non-cardiac dyspnoea.MethodsWe included consecutive hospitalised patients with presumed HF or dyspnoea and excluded patients with acute coronary syndrome, estimated glomerular filtration rate <30 mL/min/1.73 m² or low NT-proBNP (<296 ng/L). Higher age-adjusted NT-proBNP values excluded patients with presumptive non-cardiac dyspnoea. Contemporary criteria for HFpEF and diastolic dysfunction were assessed, and we adjudicated whether acute decompensated HF (ADHF) had been the primary diagnosis.ResultsOf 707 eligible patients, we included 370 patients of whom 75 had non-cardiac dyspnoea. Of these, 10% (38/370) had no cardiac dysfunction. Cardiac dysfunction consisted of 18.4%, HFvhd, 30.1% HFrEF, 10.2% HFmrEF and 41.3% HFpEF. HFpEF was twice as common in presumptive non-cardiac dyspnoea versus cardiac dyspnoea (71% vs 34%, p<0.0001). However, adjudicated ADHF was the primary diagnosis in 80% of HFrEF, 62% of HFmrEF and just 28% of HFpEF.ConclusionHF according to contemporary criteria applied to 90% of patients admitted with dyspnoea and elevated NT-proBNP irrespective of the presumptive cause of dyspnoea, of whom 10% had HFmrEF and 41% HFpEF. However, significant non-cardiac diagnoses related to 9 out of 10 with HFpEF with pulmonary disease as the predominant adjudicated problem.
Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the UK
Authors: Rinciog Claudia I , Sawyer Laura M , Diamantopoulos Alexander , Elkind Mitchell S V , Reynolds Matthew , Tsintzos Stylianos I , Ziegler Paul D , Quiroz Maria E , Wolff Claudia , Witte Klaus K 
Published: June 2019

ObjectiveTo evaluate the cost-effectiveness of insertable cardiac monitors (ICMs) compared with standard of care (SoC) for detecting atrial fibrillation (AF) in patients at high risk of stroke (CHADS2>2), using a UK National Health Service (NHS) perspective.MethodsUsing patient characteristics and clinical data from the REVEAL AF trial, a Markov model assessed the cost-effectiveness of detecting AF with an ICM compared with SoC. Costs and benefits were extrapolated across modelled patient lifetime. Ischaemic and haemorrhagic strokes, intracranial and extracranial haemorrhages and minor bleeds were modelled. Diagnostic and device costs were included, plus costs of treating stroke and bleeding events and costs of oral anticoagulants (OACs). Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3.5% per annum. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken.ResultsThe total per-patient cost for ICM was £13 360 versus £11 936 for SoC (namely, annual 24 hours Holter monitoring). ICMs generated a total of 6.50 QALYs versus 6.30 for SoC. The incremental cost-effectiveness ratio (ICER) was £7140/QALY gained, below the £20 000/QALY acceptability threshold. ICMs were cost-effective in 77.4% of PSA simulations. The number of ICMs needed to prevent one stroke was 21 and to cause a major bleed was 37. ICERs were sensitive to assumed proportions of patients initiating or discontinuing OAC after AF diagnosis, type of OAC used and how intense the traditional monitoring was assumed to be under SoC.ConclusionsThe use of ICMs to identify AF in a high-risk population is cost-effective for the UK NHS.
Additive effect of cerebral atrophy on cognition in dementia-free elderly with cerebrovascular disease
Authors: Xu Xin , Phua April , Collinson Simon L , Hilal Saima , Ikram Mohammad Kamran , Wong Tien Yin , Cheng Ching Yu , Venketasubramanian Narayanaswamy , Chen Christopher 
Published: June 2019

ObjectiveTo explore the additive effect of neurodegenerative diseases, measured by atrophy, on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease (CeVD).MethodsThe present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study. Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging. The weighted CeVD burden scale comprising markers of both small- and large-vessel diseases was applied, with a score of ≥2, indicating significant CeVD burden. Cortical atrophy (CA) and medial temporal atrophy (MTA) were graded using the global cortical atrophy scale and Schelten’s scale, respectively. Global and domain-specific (attention, executive function, language, visuomotor speed, visuoconstruction, visual memory, and verbal memory) neurocognitive performance was measured using a locally validated neuropsychological battery (Vascular Dementia Battery, VDB).ResultsA total of 819 dementia-free participants were included in the analysis. Among none-mild CeVD subjects, there was no significant difference in the global cognitive performance across atrophy groups (no atrophy, CA, and CA+MTA). However, in moderate-severe CeVD subjects, CA+MTA showed significantly worse global cognitive performance compared with those with CA alone (mean difference=−0.35, 95% CI −0.60 to −0.11, p=0.002) and those without atrophy (mean difference=−0.46, 95% CI −0.74 to −0.19, p<0.001, p<0.001). In domain-specific cognitive performance, subjects with CA+MTA performed worse than other groups in visual memory (p=0.005), executive function (p=0.001) and visuomotor speed (p<0.001) in moderate-severe CeVD but not in none-mild CeVD.Conclusions and relevanceAtrophy and moderate-severe CeVD burden showed an additive effect on global and domain-specific cognitive performance. This study highlights the importance of investigating the mechanisms of clinico-pathological interactions between neurodegenerative processes and vascular damage, particularly in the pre-dementia stage.
STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis
Authors: Pan Aiqun , Tan Yuying , Wang Zhihao , Xu Guoliang 
Published: June 2019

As an inflammatory disease afflicting the heart muscle, autoimmune myocarditis (AM) represents one of the foremost causes of heart failure. Accumulating evidence has implicated microRNAs (miRNAs) in the process of inflammation and autoimmunity. Hence, the current study aimed to investigate the mechanism by which miR-141-3p influences experimental AM (EAM). An EAM mouse model was established using 6-wk old male BALB/c mice, after which the expression of miR-141-3p and STAT4 was measured. Gain-of-function and loss-of-function investigations were performed to identify the functional role of miR-141-3p and STAT4 in EAM. Heart weight-to-body weight ratio, cardiac function, and degree of inflammation, as well as the levels of inflammation factors (IFN-γ, TNF-α, IL-2, IL-6, and IL-17) in the serum were detected. STAT4 was subsequently verified to be upregulated, and miR-141-3p was downregulated in the EAM mice. Furthermore, the overexpression of miR-141-3p or silencing of STAT4 was observed to reduce the heart weight-to-body weight ratio of EAM mice and improve cardiac function, while alleviating the degree of inflammatory cell infiltration in the myocardial tissue. Meanwhile, the overexpression of miR-141-3p was identified to diminish serum inflammatory factor levels by downregulating STAT4. Additionally, miR-141-3p could bind to STAT4 to downregulate its expression, ultimately mitigating inflammation and inducing an anti-inflammatory effect in EAM mice. Taken together, upregulation of miR-141-3p alleviates the inflammatory response in EAM mice by inhibiting STAT4, providing a promising intervention target for the molecular treatment of AM. NEW & NOTEWORTHY miR-141-3p is poorly expressed, and STAT4 is upregulated in experimental autoimmune myocarditis (EAM) mice. Overexpressing miR-141-3p inhibits EAM. miR-141-3p binds to and suppresses STAT4 expression. miR-141-3p overexpression inhibits inflammatory factors by downregulating STAT4. This study provides new insights into the treatment of autoimmune myocarditis.
Integrative Copy Number Analysis of Uveal Melanoma Reveals Novel Candidate Genes Involved in Tumorigenesis Including a Tumor Suppressor Role for PHF10/BAF45a
Authors: Anbunathan Hima , Verstraten Ruth , Singh Arun D. , Harbour J. William , Bowcock Anne M. 
Published: June 2019

Abstract

Purpose:
Uveal melanoma is a primary malignancy of the eye with oncogenic mutations in GNAQ, GNA11, or CYSLTR2, and additional mutations in BAP1 (usually associated with LOH of Chr 3), SF3B1, or EIF1AX. There are other characteristic chromosomal alterations, but their significance is not clear.

Experimental Design:
To investigate genes driving chromosomal alterations, we integrated copy number, transcriptome, and mutation data from three cohorts and followed up key findings.

Results:
We observed significant enrichment of transcripts on chromosomes 1p, 3, 6, 8, and 16q and identified seven shared focal copy number alterations (FCNAs) on Chr 1p36, 2q37, 3, 6q25, 6q27, and 8q24. Integrated analyses revealed clusters of genes in focal copy number regions whose expression was associated with metastasis and worse overall survival. This included genes from Chr 1p36, 3p21, and 8q24.3. At Chr 6q27, we identified two tumors with homozygous deletion of PHF10/BAF45a and one with a frameshift mutation with concomitant loss of the wild-type allele. Downregulation of PHF10 in uveal melanoma cell lines and tumors altered a number of biological pathways including development and adhesion. These findings provide support for a role for PHF10 as a novel tumor suppressor at Chr 6q27.

Conclusions:
Integration of copy number, transcriptome, and mutation data revealed novel candidate genes playing a role in uveal melanoma pathogenesis and a potential tumor suppressor role for PHF10.
Targeting Topoisomerase I in the Era of Precision Medicine
Authors: Thomas Anish , Pommier Yves 
Published: June 2019

Abstract
Irinotecan and topotecan have been widely used as anticancer drugs for the past 20 years. Because of their selectivity as topoisomerase I (TOP1) inhibitors that trap TOP1 cleavage complexes, camptothecins are also widely used to elucidate the DNA repair pathways associated with DNA–protein cross-links and replication stress. This review summarizes the basic molecular mechanisms of action of TOP1 inhibitors, their current use, and limitations as anticancer agents. We introduce new therapeutic strategies based on novel TOP1 inhibitor chemical scaffolds including the indenoisoquinolines LMP400 (indotecan), LMP776 (indimitecan), and LMP744, and on tumor-targeted delivery TOP1 inhibitors using liposome, PEGylation, and antibody–drug conjugates. We also address how tumor-specific determinants such as homologous recombination defects (HRD and BRCAness) and Schlafen 11 (SLFN11) expression can be used to guide clinical application of TOP1 inhibitors in combination with DNA damage response inhibitors including PARP, ATR, CHEK1, and ATM inhibitors.
Exercise as a Candidate Antitumor Strategy: A Window into the Future
Authors: Koelwyn Graeme J. , Jones Lee W. 
Published: June 2019

Abstract
Observational findings suggest exercise is associated with improved outcomes in early-stage breast cancer. However, whether exercise has biological activity in patients with breast cancer has not been investigated. Preoperative window of opportunity studies provide a setting in which to test the short-term effects of novel treatment strategies on validated surrogates.
See related article by Ligibel et al., p. 5398
Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank
Authors: Farmer Ruth E. , Mathur Rohini , Schmidt A. Floriaan , Bhaskaran Krishnan , Fatemifar Ghazaleh , Eastwood Sophie V. , Finan Chris , Denaxas Spiros , Smeeth Liam , Chaturvedi Nish 
Published: June 2019

Background
The “healthy obese” hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding.

Methods and Results

We conducted a cohort study using the
UK
Biobank (n=452 931). Baseline body mass index (
BMI)
was used to quantify adiposity and handgrip strength (
HGS
) used for muscle quality. Outcomes were fatal and non‐fatal cardiovascular disease, and mortality. As a secondary analysis we used waist‐hip‐ratio or fat mass percentage instead of
BMI
, and skeletal muscle mass index instead of
HGS
. In a subsample, we used gene scores for
BMI
, waist‐hip‐ratio and
HGS
in a Mendelian randomization (
MR
).
BMI
defined obesity was associated with an increased risk of all outcomes (hazard ratio [
HR
] range 1.10–1.82). Low
HGS
was associated with increased risks of cardiovascular and all‐cause mortality (
HR
range 1.39–1.72).
HR
s for the association between low
HGS
and cardiovascular disease events were smaller (
HR
range 1.05–1.09). There was no suggestion of an interaction between
HGS
and
BMI
to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted
HGS
was associated with an increased risk of mortality (
HR
range 1.08–1.19).

Conclusions

Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower
HGS
was associated with increased risks of mortality in both observational and
MR
analyses, suggesting reverse causality may not be the sole explanation.
Sea Level at the Coast from Video-Sensed Waves: Comparison to Tidal Gauges and Satellite Altimetry
Authors: Ondoa G. Abessolo , Almar R. , Castelle B. , Testut L. , Léger F. , Sohou Z. , Bonou F. , Bergsma E. W. J. , Meyssignac B. , Larson M. 
Published: June 2019

AbstractNearshore complex and energetic hydrodynamic conditions make observing evolving processes during extreme and short-term events difficult. In particular, total sea levels at the coast are hard to measure with current techniques. Sea level is commonly measured with tidal gauges and spaceborne altimetry, which lack essential details of spatial and wave-related sea level variability along the coast. Hence, novel techniques, adapted to nearshore areas, are required. This paper presents the first-time use of video cameras to derive the total sea level at the coast. This novel approach consists of estimating time-varying total water levels by applying a celerity-based depth inversion method, which is conventionally used to estimate bathymetry from video. The video-derived total sea levels are compared to sea levels derived from an in situ acoustic Doppler current profiler (ADCP), the nearest tide gauge, and altimetry. A tidal harmonic analysis is performed on the video-derived water levels, yielding an accurate determination of the dominant tidal harmonics. However, it remains difficult to separate bathymetric changes due to the waves on beaches when rapid morphological changes occur under energetic conditions. Nonetheless, video-derived water-level anomalies are in good agreement with state-of-the-art altimetry products. Although there is still work to be done, the results show the potential to measure total sea level at the coast using video camera systems.
Concentration, distribution, and influence of aging on the 18 kDa translocator protein in human brain: Implications for brain imaging studies
Authors: Tong Junchao , Williams Belinda , Rusjan Pablo M. , Mizrahi Romina , Lacapère Jean-Jacques , McCluskey Tina , Furukawa Yoshiaki , Guttman Mark , Ang Lee-Cyn , Boileau Isabelle , Meyer Jeffrey H , Kish Stephen J 
Published: June 2019

Positron emission tomography (PET) imaging of the translocator protein (TSPO) is widely used as a biomarker of microglial activation. However, TSPO protein concentration in human brain has not been optimally quantified nor has its regional distribution been compared to TSPO binding. We determined TSPO protein concentration, change with age, and regional distribution by quantitative immunoblotting in autopsied human brain. Brain TSPO protein concentration (>0.1 ng/µg protein) was higher than those reported by in vitro binding assays by at least 2 to 70 fold. TSPO protein distributed widely in both gray and white matter regions, with distribution in major gray matter areas ranked generally similar to that of PET binding in second-generation radiotracer studies. TSPO protein concentration in frontal cortex was high at birth, declined precipitously during the first three months, and increased modestly during adulthood/senescence (10%/decade; vs. 30% for comparison astrocytic marker GFAP). As expected, TSPO protein levels were significantly increased (+114%) in degenerating putamen in multiple system atrophy, providing further circumstantial support for TSPO as a gliosis marker. Overall, findings show some similarities between TSPO protein and PET binding characteristics in the human brain but also suggest that part of the TSPO protein pool might be less available for radioligand binding.