bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the influence of socioeconomic status on the association between combinations of lifestyle factors and adverse health outcomes: a systematic review protocol
Authors: Foster Hamish , Polz Peter , Mair Frances , Gill Jason , O'Donnell Catherine A 
Published: May 2021

IntroductionCombinations of unhealthy lifestyle factors are strongly associated with mortality, cardiovascular disease (CVD) and cancer. It is unclear how socioeconomic status (SES) affects those associations. Lower SES groups may be disproportionately vulnerable to the effects of unhealthy lifestyle factors compared with higher SES groups via interactions with other factors associated with low SES (eg, stress) or via accelerated biological ageing. This systematic review aims to synthesise studies that examine how SES moderates the association between lifestyle factor combinations and adverse health outcomes. Greater understanding of how lifestyle risk varies across socioeconomic spectra could reduce adverse health by (1) identifying novel high-risk groups or targets for future interventions and (2) informing research, policy and interventions that aim to support healthy lifestyles in socioeconomically deprived communities.Methods and analysisThree databases will be searched (PubMed, EMBASE, CINAHL) from inception to March 2020. Reference lists, citations and grey literature will also be searched. Inclusion criteria are: (1) prospective cohort studies; (2) investigations of two key exposures: (a) lifestyle factor combinations of at least three lifestyle factors (eg, smoking, physical activity and diet) and (b) SES (eg, income, education or poverty index); (3) an assessment of the impact of SES on the association between combinations of unhealthy lifestyle factors and health outcomes; (4) at least one outcome from—mortality (all cause, CVD and cancer), CVD or cancer incidence. Two independent reviewers will screen titles, abstracts and full texts of included studies. Data extraction will focus on cohort characteristics, exposures, direction and magnitude of SES effects, methods and quality (via Newcastle-Ottawa Scale). If appropriate, a meta-analysis, pooling the effects of SES, will be performed. Alternatively, a synthesis without meta-analysis will be conducted.Ethics and disseminationEthical approval is not required. Results will be disseminated via peer-reviewed publication, professional networks, social media and conference presentations.PROSPERO registration numberCRD42020172588.
Pegfilgrastim safety and efficacy on the last chemotherapy day versus the next: systematic review and meta-analysis
Authors: Ma Xiaohua , Kang Jian , Li Yufang , Zhang Xiaojian 
Published: May 2021

ObjectivesTo investigate the efficacy and safety of pegfilgrastim administered on the day of chemotherapy completion (same day) versus at least 1 day after chemotherapy (next day).MethodsWe searched relevant literature published before April 2020 from the following databases: Embase, PubMed, Cochrane databases and Web of science.ResultsOne randomised controlled trial and 12 observational studies met all of the prespecified criteria for eligibility. The meta-analysis showed a significantly higher febrile neutropenia (FN) rate for the same-day group than that for the next-day arm in the first chemotherapy cycle (OR=2.56, 95% CI 1.19 to 5.48, p=0.02), and in all chemotherapy cycles (OR=1.54, 95% CI 1.29 to 1.84, p<0.00001). Results of subgroup analysis showed a higher FN rate in the same-day arm than in the next-day group for patients with breast cancer (OR=5.50, 95% CI 2.29 to 13.23, p=0.0001) and lymphoma (OR=1.53, 95% CI 1.00 to 2.34, p=0.05). The pooled analysis of studies on gynaecological malignancies showed that patients in the same-day group had a higher incidence of bone pain (OR=1.30, 95% CI 1.01 to 1.68, p=0.04) and a lower incidence of chemotherapy delay (OR=0.71, 95% CI 0.53 to 0.96, p=0.03) compared with the next-day group.ConclusionsSame-day administration of pegfilgrastim resulted in increased incidence of FN compared with the next-day schedule. This is especially true for patients with breast cancer or lymphoma. These results do not support same-day administration of pegfilgrastim .
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial
Authors: Carreira Suzanne , Porta Nuria , Arce-Gallego Sara , Seed George , Llop-Guevara Alba , Bianchini Diletta , Rescigno Pasquale , Paschalis Alec , Bertan Claudia , Baker Chloe , Goodall Jane , Miranda Susana , Riisnaes Ruth , Figueiredo Ines , Ferreira Ana , Pereira Rita , Crespo Mateus , Gurel Bora , Nava Rodrigues Daniel , Pettitt Stephen J. , Yuan Wei , Serra Violeta , Rekowski Jan , Lord Christopher J. , Hall Emma , Mateo Joaquin , de Bono Johann S. 
Published: May 2021

Abstract

PARP inhibitors are approved for treating advanced prostate cancers (APC) with various defective DNA repair genes; however, further studies to clinically qualify predictive biomarkers are warranted. Herein we analyzed TOPARP-B phase II clinical trial samples, evaluating whole-exome and low-pass whole-genome sequencing and IHC and IF assays evaluating ATM and RAD51 foci (testing homologous recombination repair function). BRCA1/2 germline and somatic pathogenic mutations associated with similar benefit from olaparib; greater benefit was observed with homozygous BRCA2 deletion. Biallelic, but not monoallelic, PALB2 deleterious alterations were associated with clinical benefit. In the ATM cohort, loss of ATM protein by IHC was associated with a better outcome. RAD51 foci loss identified tumors with biallelic BRCA and PALB2 alterations while most ATM- and CDK12-altered APCs had higher RAD51 foci levels. Overall, APCs with homozygous BRCA2 deletion are exceptional responders; PALB2 biallelic loss and loss of ATM IHC expression associated with clinical benefit.

Significance:
Not all APCs with DNA repair defects derive similar benefit from PARP inhibition. Most benefit was seen among patients with BRCA2 homozygous deletions, biallelic loss of PALB2, and loss of ATM protein. Loss of RAD51 foci, evaluating homologous recombination repair function, was found primarily in tumors with biallelic BRCA1/2 and PALB2 alterations.
This article is highlighted in the In This Issue feature, p. 2659
Avaliação de sintomas na distrofia muscular de Duchenne: uma estratégia de cuidado paliativo
Authors: Pavão Josiane Rosires , Lizzi Elisângela Aparecida da Silva , Souza Mariana Angélica de , Sobreira Cláudia Ferreira da Rosa , Chaves Thais Cristina , Mattiello-Sverzut Ana Claudia 
Published: May 2021

Symptom assessment, in Duchenne Muscular Dystrophy (DMD), allows an adequate treatment, and the Edmonton Symptom Assessment System (ESAS) assess it: evaluating clinical problems of patients in palliative care (pain, tiredness, drowsiness, nausea, appetite, shortness of breath, depression, anxiety, and well-being). Objective: To verify if patients with DMD understand the terms of the ESAS and if their symptoms could be assessed using this instrument. Methods: Ten patients with DMD were cross-sectional evaluated in relation to the understanding of the ESAS items, capacity to describe symptom (using the ESAS and the Faces Scale) and the Motor Function Measure. The patient’s symptom by ESAS was also classified by evaluator. A descriptive and correlation (Spearman's correlation coefficient) analysis of data was performed. Results: All patients understood the symptoms of pain, tiredness, drowsiness, depression (sadness), and well-being. However, some patients did not understand the symptoms of nausea, appetite, shortness of breath. The general mean of all symptoms assessed by the ESAS was below 5 points. For the symptom ‘depression’ and ‘anxiety’, a strong correlation was found between the results of the ESAS and the Face scale (r= 0.64, and r= 0.65, respectively). Additionally, a perfect and strong correlation, respectively, was found between the ESAS completed by the patient and the evaluator for the items '‘depression’," and ‘anxiety’ (r= 1.0)" and a ‘drowsiness’ (r= 0.82). Conclusion: DMD patients understood the ESAS terms and graded their symptoms using this instrument. Therefore, it is not necessary to change the ESAS terms to assess patients with DMD.
Seguimento de pessoas acometidas por doenças cerebrovasculares em um hospital regional amazônico: uma metodologia WHO STEP Stroke
Authors: Fernandes Tiotrefis Gomes , Baptista Pedro Porto Alegre , Costa Jonathas Gonçalves da , Lotufo Paulo Andrade , Campos Tania Fernandes 
Published: May 2021

The WHO STEP Stroke is a tool developed to monitor cases of cerebrovascular and allow comparison of its incidence throughout the world. Objective: To describe the sociodemographic profile and functionality of stroke inpatients admitted in Coari´s Regional Hospital and followed up one month after admittance. Method: This is a prospective, descriptive observational and follow-up study of cases between October 2010 and October 2011. In this study, we used the first step (Step 1) of the WHO STEP Stroke to assess stroke hospitalization in Coari-AM Twenty-three patients were monitored with a standard questionnaire up to two days after hospitalization, 10 days, and 28 after hospitalization. Results: The studied population had average age of 72.8 (SD= 12.4) years, mostly men (65.7%), brown (65.2%), and hypertensive (95.7%), with a hospital incidence of 30 cases for 100.000 people, and mortality in 10 days of 30.4% and 28 days of 34.8%. The neurological impairment at hospitalization had a median of 28 (IIQ= 15-38) points, with 73.9% classified as severe. There was an impairment in functionality among the survivors. Conclusion: This study showed the profile of hospital admittance for cerebrovascular disease in this city to be mainly composed by older men, brown, with no formal study, low income, and history of systemic arterial hypertension and diabetes. The hospital incidence for stroke was 30 (per 100.000) in Coari-AM, with severe neurological impairment at admission, with high mortality rates, and functional deficits 28 days after the event when compared to other regions in Brazil and in the world.
Genetic Ablation of Transmembrane Prolyl 4-Hydroxylase Reduces Atherosclerotic Plaques in Mice
Authors: Määttä Jenni , Serpi Raisa , Hörkkö Sohvi , Izzi Valerio , Myllyharju Johanna , Dimova Elitsa Y. , Koivunen Peppi 
Published: May 2021

Objective:
Atherosclerosis is a key component of cardiovascular diseases. We set out to study here whether genetic ablation of P4H-TM (transmembrane prolyl 4-hydroxylase) could protect against atherosclerosis as does inhibition of the other 3 classical HIF-P4Hs (hypoxia-inducible factor prolyl 4-hydroxylases).

Approach and Results:

We generated a double knockout mouse line deficient in P4H-TM and LDL (low-density lipoprotein) receptor (
P4h-tm
−/−
/Ldlr
−/−
) and subjected these mice to a high-fat diet for 13 weeks. The double knockout mice had less atherosclerotic plaques in their full-length aorta than their
P4h-tm
+/+
/Ldlr
−/−
counterparts and also had lower serum triglyceride levels on standard laboratory diet and high-fat diet, higher levels of IgM autoantibodies against Ox-LDL (oxidized LDL), and significantly higher LPL (lipoprotein lipase) protein levels in white adipose tissue and sera. RNA-sequencing analysis revealed changes in expression of mRNAs in multiple pathways including lipid metabolism and immunologic response in the
P4h-tm
−/−
/
Ldlr
−/−
livers as compared with
P4h-tm
+/+
/
Ldlr
−/−
.

Conclusions:
Our data identify P4H-TM inhibition as a potential novel immuno-metabolic mechanism for intervening in the pathology of atherosclerosis, as hypertriglyceridemia is an individual risk factor for atherosclerosis, and IgM antibodies to Ox-LDL and increased lipoprotein lipase have been associated with protection against it.
Long-Term Outcomes of the Coarctation of the Aorta Stent Trials
Authors: Holzer Ralf J. , Gauvreau Kimberlee , McEnaney Kerry , Watanabe Hanano , Ringel Richard 
Published: May 2021

Background:
Long-term outcome data of stent-implantation for coarctation of the aorta are limited. We report up to 5 years of postimplant follow-up in patients enrolled into the COAST (Coarctation of the Aorta Stent Trial) and the COAST II trial (Covered Cheatham-Platinum Stents for Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta), evaluating the bare and Covered Cheatham-Platinum Stents for the treatment of coarctation of the aorta and associated aortic wall injury.

Methods:
Data was prospectively collected during the 2 multi-center studies, enrolling 248 patients (COAST: n=121, COAST II: n=127). Late follow-up data (48–60 month) was compared with immediate (1 month) and early (12 months) follow-up.

Results:
There was a notable decrease in the use of antihypertensive medication, from 53% at immediate, to 42% at early, and 29% at late follow-up. The cumulative incidence of stent fractures was 0% immediately, 2.9% at early, and 24.4% at late follow-up. Independent predictors for stent fractures at late follow-up were age <18 years, male sex, minimum stent diameter ≥12 mm, and use of bare metal stent. The cumulative incidence of reintervention was 1.6% at immediate, 5.1% at early, and 21.3% at late follow-up. Independent predictors for reinterventions at late follow-up were age <18 years, post implantation systolic arm-leg blood pressure gradient ≥10 mm Hg, minimum stent diameter at implantation <12 mm, and initial coarctation minimum diameter <6 mm. There were 13 patients with aortic aneurysms, with a cumulative incidence of 6.3% at late follow-up.

Conclusions:
Coarctation stenting is effective at maintaining obstruction relief up to 60 months postimplant with reduction in the number of patients requiring antihypertensive medication. However, an increase in-stent fractures and reinterventions were observed between medium and long-term follow-up. Covered stents appear to confer some protection from the development of stent fractures but do not provide complete protection from late aneurysm formation.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT00552812 and NCT01278303.
COL5A1
Variants Cause Aortic Dissection by Activating TGF‐β‐Signaling Pathway
Authors: Chen Peng , Yu Bo , Li Zongzhe , Chen Yanghui , Sun Yang , Wang Dao Wen 
Published: May 2021

Background

Aortic dissection (AD) is one of the most life‐threatening cardiovascular diseases that exhibit high genetic heterogeneity. However, it is unclear whether variants within the
COL5A1
gene can cause AD. Therefore, we intend to determine whether
COL5A1
is a causative gene of AD.

Methods and Results

We performed targeted sequencing in 702 patients with unrelated sporadic AD and 163 matched healthy controls using a predesigned panel with 152 vessel matrix‐related genes. As a result, we identified that 11 variants in
COL5A1
caused AD in 11 out of the 702 patients with AD. Furthermore,
Col5a1
knockout (

Col5a1
+/−

) rats were generated through the CRISPR/Cas9 system. Although there was no spontaneous AD, electron microscopy revealed a fracture of elastic fibers and disarray of collagenous fibers in 6‐week‐old

Col5a1
+/−

rats, but not in WT rats (93.3% versus 0.0%,
P
<0.001). Three‐week‐old rats were used to induce the AD phenotype with β‐aminopropionitrile monofumarate for 4 weeks followed by angiotensin II for 72 hours. The β‐aminopropionitrile monofumarate and angiotensin II‐treated rat model confirmed that

Col5a1
+/−

rats had considerably higher AD incidence than WT rats. Subsequent mechanism analyses demonstrated that the transforming growth factor‐β‐signaling pathway was significantly activated in

Col5a1
+/−

rats.

Conclusions

Our findings, for the first time, revealed a relationship between variants in
COL5A1
and AD via targeted sequencing in 1.57% patients with sporadic aortic dissection. The
Col5a1
knockout rats exhibited AD after an intervention, indicating that
COL5A1
is a causative gene of AD. Activation of the transforming growth factor‐β‐signaling pathway may be implicated in the pathogenesis of this kind of AD.
Can Children With Perinatal Stroke Use a Simple Brain Computer Interface?
Authors: Jadavji Zeanna , Zhang Jack , Paffrath Brett , Zewdie Ephrem , Kirton Adam 
Published: May 2021

Background and Purpose:
Perinatal stroke is the leading cause of hemiparetic cerebral palsy resulting in lifelong disability for millions of people worldwide. Options for motor rehabilitation are limited, especially for the most severely affected children. Brain computer interfaces (BCIs) sample brain activity to allow users to control external devices. Functional electrical stimulation enhances motor recovery after stroke, and BCI-activated functional electrical stimulation was recently shown to improve upper extremity function in adult stroke. We aimed to determine the ability of children with perinatal stroke to operate a simple BCI.

Methods:
Twenty-one children with magnetic resonance imaging–confirmed perinatal stroke (57% male, mean [SD] 13.5 [2.6] years, range 9–18) were compared with 24 typically developing controls (71% male, mean age [SD] 13.7 [3.7] years, range 6–18). Participants trained on a simple EEG-based BCI over 2 sessions (10 trials each) utilizing 2 different mental imagery strategies: (1) motor imagery (imagine opening and closing of hands) and (2) goal oriented (imagine effector object moving toward target) to complete 2 tasks: (1) drive a remote controlled car to a target and (2) move a computer cursor to a target. Primary outcome was Cohen Kappa with a score >0.40 suggesting BCI competence.

Results:

BCI performance was comparable between stroke and control participants. Mean scores were 0.39 (0.18) for stroke versus 0.42 (0.18) for controls (t[42]=0.478,
P
=0.94). No difference in performance between venous (M=0.45, SD=0.29) and arterial (M=0.34, SD=0.22) stroke (t[82]=1.89,
P
=0.090) was observed. No effect of task or strategy was observed in the stroke participants. Over 90% of stroke participants demonstrated competency on at least one of the 4 task-strategy combinations.

Conclusions:
Children with perinatal stroke can achieve proficiency in basic tasks using simple BCI systems. Future directions include exploration of BCI-functional electrical stimulation systems for rehabilitation for children with hemiparesis and other forms of cerebral palsy.
Hospital Factors, Performance on Process Measures After Transient Ischemic Attack, and 90-Day Ischemic Stroke Incidence
Authors: Levine Deborah A. , Perkins Anthony J. , Sico Jason J. , Myers Laura J. , Phipps Michael S. , Zhang Ying , Bravata Dawn M. 
Published: May 2021

Background and Purpose:
We determined the association between hospital factors, performance on transient ischemic attack (TIA) process measures, and 90-day ischemic stroke incidence.

Methods:
Longitudinal analysis of retrospectively obtained data on 9168 veterans ≥18 years with TIA presenting to the emergency department or inpatient unit at 69 Veterans Affairs hospitals with ≥10 eligible patients per year in fiscal years 2015 to 2018. Process measures were high/moderate potency statin within 7 days of discharge, antithrombotic by day 2, and hypertension control (<140/90 mm Hg) at 90 days. The outcome was 90-day stroke incidence.

Results:

During the 4-year study period, hospitals significantly increased statin use (adjusted odds ratio [aOR] per 1-year increase, 1.24 [95% CI, 1.17–1.32];
P
<0.001), whereas neither hypertension control (
P
=0.44) nor antithrombotic use (
P
=0.82) improved over time. Hospitals that admitted a higher proportion of TIA patients versus emergency department discharge had significantly greater use of statins (aOR per 10-percentage point increase in the proportion of TIA patients admitted, 1.09 [1.03–1.16];
P
=0.003) and antithrombotics (aOR per 10-percentage point increase in TIA patients admitted, 1.14 [1.06–1.23];
P
<0.001). Hospitals with higher emergency physician staffing and lower TIA patient volume had greater use of antithrombotics (aOR per 1 full-time physician increase, 1.05 [1.01–1.08];
P
=0.008 and aOR per 10-patient decrease in volume, 1.09 [1.01–1.16];
P
=0.02). Higher emergency physician staffing was associated with lower 90-day stroke incidence (aOR per 1 full-time physician increase, 0.96 [0.92–0.99];
P
=0.02) but other hospital factors were not.

Conclusions:
Hospitals admitting higher percentages of TIA patients and having higher emergency physician staffing have greater performance on select guideline-concordant process measures for TIA. Higher emergency physician staffing was associated with improved outcomes 90 days after TIA.
P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack
Authors: Li Zi-Xiao , Xiong Yunyun , Gu Hong-Qiu , Fisher Marc , Xian Ying , Johnston S. Claiborne , Wang Yong-Jun 
Published: May 2021

Background and purpose:
We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack.

Methods:

Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and
I
2
test.

Results:

Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68–0.83],
I
2
=0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89],
I
2
=0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17],
I
2
=0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29],
I
2
=94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39],
I
2
=0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08],
I
2
=41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75–4.67],
I
2
=0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08],
I
2
=37%) but not within 21 days or clopidogrel.

Conclusions:
In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.