bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Chronic Obstructive Pulmonary Disease in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PARAGON‐HF
Authors: Mooney Leanne , Hawkins Nathaniel M. , Jhund Pardeep S. , Redfield Margaret M. , Vaduganathan Muthiah , Desai Akshay S. , Rouleau Jean L. , Minamisawa Masatoshi , Shah Amil M. , Lefkowitz Martin P. , Zile Michael R. , Van Veldhuisen Dirk J. , Pfeffer Marc A. , Anand Inder S. , Maggioni Aldo P. , Senni Michele , Claggett Brian L. , Solomon Scott D. , McMurray John J. V. 
Published: November 2021

Background
Little is known about the impact of chronic obstructive pulmonary disease (COPD) in patients with heart failure with preserved ejection fraction (HFpEF).

Methods and Results

We examined outcomes in patients with heart failure with preserved ejection fraction, according to COPD status, in the PARAGON‐HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and cardiovascular death. Of 4791 patients, 670 (14%) had COPD. Patients with COPD were more likely to be men (58% versus 47%;
P
<0.001) and had worse New York Heart Association functional class (class III/IV 24% versus 19%), worse Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (69 versus 76;
P
<0.001) and more frequent history of heart failure hospitalization (54% versus 47%;
P
<0.001). The decrement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores with COPD was greater than for other common comorbidities. Patients with COPD had echocardiographic right ventricular enlargement, higher serum creatinine (100 μmol/L versus 96 μmol/L) and neutrophil‐to‐lymphocyte ratio (2.7 versus 2.5), than those without COPD. After multivariable adjustment, COPD was associated with worse outcomes: adjusted rate ratio for the primary outcome 1.51 (95% CI, 1.25–1.83), total heart failure hospitalization 1.54 (95% CI, 1.24–1.90), cardiovascular death (adjusted hazard ratio [HR], 1.42; 95% CI, 1.10–1.82), and all‐cause death (adjusted HR, 1.52; 95% CI, 1.25–1.84). COPD was associated with worse outcomes than other comorbidities and Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores declined more in patients with COPD than in those without.

Conclusions
Approximately 1 in 7 patients with heart failure with preserved ejection fraction had concomitant COPD, which was associated with greater functional limitation and a higher risk of heart failure hospitalization and death.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier:
NCT01920711
.
Drug‐Coated Balloon Versus Plain Balloon Angioplasty for Hemodialysis Dysfunction: A Meta‐Analysis of Randomized Controlled Trials
Authors: Liu Chenyu , Wolfers Matthew , Awan Bint‐e Zainab , Ali Issa , Lorenzana Adrian Michael , Smith Quinn , Tadros George , Yu Qian 
Published: November 2021

Background
Both drug‐coated balloon (DCB) angioplasty and conventional plain balloon angioplasty (PBA) can be implemented to treat hemodialysis dysfunction. The present study aims to compare the safety and efficacy of these 2 approaches by conducting a meta‐analysis of available randomized controlled trials.

Methods and Results

PubMed, Cochrane Library, and Embase databases were queried from establishment to January 2021. A total of 18 randomized controlled trials including 877 and 875 patients in the DCB and PBA groups, respectively, were included in the present meta‐analysis. Target lesion primary patency, circuit patency, target lesion revascularization, and mortality were pooled. Odds ratios (ORs) were reported with 95% CIs. Publication bias was analyzed with funnel plot and Egger test. Target lesion primary patency was higher among patients who underwent DCB (OR, 2.93 [95% CI, 2.13–4.03],
P
<0.001 at 6 months; OR, 2.47 [95% CI, 1.53–3.99],
P
<0.001 at 1 year). Also, the DCB group had a higher dialysis circuit patency at 6 months (OR, 2.42; 95% CI, 1.56–3.77 [
P
<0.001]) and 1 year (OR, 1.91; 95% CI, 1.22–3.00 [
P
=0.005]). Compared with the PBA group, the DCB group had lower odds of target lesion revascularization during follow‐up (OR, 0.43 [95% CI, 0.23–0.82],
P
=0.001 at 6 months; OR, 0.74 [95% CI, 0.32–1.73],
P
=0.490 at 1 year). The OR of mortality was comparable between 2 groups at 6 months (OR, 1.18; 95% CI, 0.42–3.33 [
P
=0.760]) and 1 year (OR, 0.93; 95% CI, 0.58–1.48 [
P
=0.750]).

Conclusions
Based on evidence from 18 randomized controlled trials, DCB angioplasty is superior to PBA in maintaining target lesion primary patency and circuit patency among patients with dialysis circuit stenosis. DCB angioplasty also reduces target lesion revascularization with a similar risk of mortality compared with PBA.
Diet‐Derived Antioxidants Do Not Decrease Risk of Ischemic Stroke: A Mendelian Randomization Study in 1 Million People
Authors: Martens Leon G. , Luo Jiao , Willems van Dijk Ko , Jukema J. Wouter , Noordam Raymond , van Heemst Diana 
Published: November 2021

Background
Dietary intake and blood concentrations of vitamins E and C, lycopene, and carotenoids have been associated with a lower risk of incident (ischemic) stroke. However, causality cannot be inferred from these associations. Here, we investigated causality by analyzing the associations between genetically influenced antioxidant levels in blood and ischemic stroke using Mendelian randomization.

Methods and Results

For each circulating antioxidant (vitamins E and C, lycopene, β‐carotene, and retinol), which were assessed as either absolute blood levels and/or high‐throughput metabolite levels, independent genetic instrumental variables were selected from earlier genome‐wide association studies (
P
<5×10
−8
). We used summary statistics for single‐nucleotide polymorphisms–stroke associations from 3 European‐ancestry cohorts (cases/controls): MEGASTROKE (60 341/454 450), UK Biobank (2404/368 771), and the FinnGen study (8046/164 286). Mendelian randomization analyses were performed on each exposure per outcome cohort using inverse variance–weighted analyses and subsequently meta‐analyzed. In a combined sample of 1 058 298 individuals (70 791 cases), none of the genetically influenced absolute antioxidants or antioxidant metabolite concentrations were causally associated with a lower risk of ischemic stroke. For absolute antioxidants levels, the odds ratios (ORs) ranged between 0.94 (95% CI, 0.85–1.05) for vitamin C and 1.04 (95% CI, 0.99–1.08) for lycopene. For metabolites, ORs ranged between 1.01 (95% CI, 0.98–1.03) for retinol and 1.12 (95% CI, 0.88–1.42) for vitamin E.

Conclusions
This study did not provide evidence for a causal association between dietary‐derived antioxidant levels and ischemic stroke. Therefore, antioxidant supplements to increase circulating levels are unlikely to be of clinical benefit to prevent ischemic stroke.
Histone Methyltransferase Dot1L Contributes to RIPK1 Kinase‐Dependent Apoptosis in Cerebral Ischemia/Reperfusion
Authors: Wang Jinghuan , Zhong Wen , Su Haibi , Xu Jie , Yang Di , Liu Xinhua , Zhu Yi Zhun 
Published: November 2021

Background
Neuron apoptosis is a pivotal process for brain damage in cerebral ischemia. Dot1L (disruptor of telomeric silencing 1‐like) is only known histone H3K79 methyltransferase. It is not clear whether the role and mechanism of Dot1L on cerebral ischemia is related to regulate neuron apoptosis.

Methods and Results
We use a combination of mice middle cerebral artery occlusion stroke and neurons exposed to oxygen‐glucose deprivation followed by reoxygenation to investigate the role and mechanism of Dot1L on cerebral ischemia. We find knockdown or inhibition of Dot1L reversed ischemia‐induced neuronal apoptosis and attenuated the neurons injury treated by oxygen‐glucose deprivation followed by reoxygenation. Further, blockade of Dot1L prevents RIPK1 (receptor‐interacting protein kinase 1)‐dependent apoptosis through increased RIPK1 K63‐ubiquitylation and decreased formation of RIPK1/Caspase 8 complexes. In line with this, H3K79me3 enrichment in the promoter region of deubiquitin‐modifying enzyme A20 and deubiquitinase cylindromatosis gene promotes the increasing expression in oxygen‐glucose deprivation followed by reoxygenation ‐induced neuronal cells, on the contrary, oxygen‐glucose deprivation followed by reoxygenation decreases H3K79me3 level in the promoter region of ubiquitin‐modifying enzyme cIAP1 (cellular inhibitors of apoptosis proteins), and both these factors ultimately cause K63‐deubiquitination of RIPK1. Importantly, knockdown or inhibition of Dot1L in vivo attenuates apoptosis in middle cerebral artery occlusion mice and reduces the extent of middle cerebral artery occlusion ‐induced brain injury.

Conclusions
These data support for the first time, to our knowledge, that Dot1L regulating RIPK1 to the apoptotic death trigger contributes to cerebral ischemia injury. Therefore, targeting Dot1L serves as a new therapeutic strategy for ischemia stroke.
A review of COVID-19 vaccination and the reported cardiac manifestations
Authors: Ho Jamie Sin Ying , Sia Ching-Hui , Ngiam Jinghao Nicholas , Loh Poay Huan , Chew Nicholas Wen Sheng , Kong William Kok-Fai , Poh Kian-Keong 
Published: November 2021

Abstract
In Singapore, 9.03 million doses of the mRNA COVID-19 vaccines by Pfizer-BioNTech and Moderna have been administered, and 4.46 million people are fully vaccinated. An additional 87,000 people have been vaccinated with vaccines in World Health Organization’s Emergency Use Listing. The aim of this review is to explore the reported cardiac adverse events associated with different types of COVID-19 vaccines. A total of 42 studies that reported cardiac side effects after COVID-19 vaccination were included in this study. Reported COVID-19 vaccine-associated cardiac adverse events were mainly myocarditis and pericarditis, most commonly seen in adolescent and young adult male individuals after mRNA vaccination. Reports of other events such as acute myocardial infarction, arrhythmia and stress cardiomyopathy were rare. Outcomes of post-vaccine myocarditis and pericarditis were good. Given the good vaccine efficacy and the high number of cases of infection, hospitalisation and death that could potentially be prevented, COVID-19 vaccine remains of overall benefit, based on the current available data.
Evaluation of blood lead among painters of buildings and cars
Authors: Ghaffarian-Bahraman Ali , Taherifard Alireza , Esmaeili Abbas , Ahmadinia Hassan , Rezaeian Mohsen 
Published: November 2021

Exposure to lead-based paints is a major threat to the health of painters. This study aimed to evaluate the blood concentration of lead (Pb) in painters of buildings and cars. The present study was a cross-sectional study in which a semi-structured questionnaire was used to collect the socio-demographic information. Lead concentration in blood samples was determined using the atomic absorption spectrometry method. A total of 32 male painters were selected based on inclusion criteria. The mean blood lead level (BLL) in the painters was 8.1 ± 4.93 μg/dL. Pb levels in car and building painters were 9.42 ± 5.5 μg/dL and 6.7 ± 1.85 μg/dL, respectively. Pb concentration in none of the blood samples was more than 30 μg/dL. The prevalence of BLL ≥ 5 μg/dL and BLL ≥ 10 μg/dL was 97% and 19%, respectively. According to the findings, the rate of BLL among car painters was higher than building painters. Considering the presence of Pb in all blood samples, it seems necessary to increase the awareness of painters about the adverse effects of lead exposure even in low concentrations. However, the sample size in this study was small and more investigations are required in this regard.
Validity and reliability of patient reported outcomes measurement information system computerized adaptive tests in systemic lupus erythematous
Authors: Moazzami Mitra , Katz Patricia , Bonilla Dennisse , Engel Lisa , Su Jiandong , Akhavan Pooneh , Anderson Nicole , Tayer-Shifman Oshrat E , Beaton Dorcas , Touma Zahi 
Published: November 2021

Background The evaluation of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive test (CAT) in adults with systemic lupus erythematous (SLE) is an emerging field of research. We aimed to examine the test–retest reliability and construct validity of the PROMIS CAT in a Canadian cohort of patients with SLE. Methods Two hundred twenty-seven patients completed 14 domains of PROMIS CAT and seven legacy instruments during their clinical visits. Test–retest reliability of PROMIS was evaluated 7–10 days from baseline using intraclass correlation coefficient (ICC (2; 1)). The construct validity of the PROMIS CAT domains was evaluated against the commonly used legacy instruments, and also in comparison to disease activity and disease damage using Spearman correlations. A multitrait-multimethod matrix (MMM) approach was used to further assess construct validity comparing selected 10 domains of PROMIS and SF-36 domains. Results Moderate to excellent reliability was found for all domains (ICC [2;1] ranging from lowest, 0.66 for Sleep Disturbance and highest, 0.93 for the Mobility domain). Comparing seven legacy instruments with 14 domains of PROMIS CAT, moderate to strong correlations (0.51–0.91) were identified. The average time to complete all PROMIS CAT domains was 11.7 min. The MMM further established construct validity by showing moderate to strong correlations (0.55–0.87) between select PROMIS and SF-36 domains; the average correlations from similar traits (convergent validity) were significantly greater than the average correlations from different traits. Conclusions These results provide evidence on the reliability and validity of PROMIS CAT in SLE in a Canadian cohort.
An Anatomic Study of the Sural Nerve Using 3-Tesla MRI: A Comparison to Cadaveric Data With Surgical Applications
Authors: Ghetti Claudio B. , Mitchell Brendon C. , Shah Vrajesh J. , Wang Wilbur , Huang Brady , Kent William T. , Foran Ian M. 
Published: November 2021

Background: The sural nerve (SN) is a sensory cutaneous nerve that is at risk of iatrogenic injury during surgery at the lateral ankle. Prior anatomic studies of the SN are limited primarily to cadaveric studies with small sample sizes. Our study analyzed a large cohort of magnetic resonance images (MRIs) of the ankle to obtain a more generalizable, in vivo sample of distal SN course. Methods: A total of 204 3-tesla MRI studies of the ankle were analyzed. Three reviewers measured the distance from the SN to various landmarks including the distal tip of the lateral malleolus (DTLM) and the lateral border of the Achilles tendon (LBA). Results: Mean vertical distance from SN to DTLM was 2.2 cm (range, 0.9-3.6 cm). Mean horizontal distance from SN to DTLM and to LBA at the level of DTLM was 1.7 cm (range, 0.8-3.0 cm) and 1.9 cm (range, 1.0-2.9 cm), respectively. Mean horizontal distance from SN to LBA at the level of superior Achilles tendon insertion onto the calcaneus (SAI) was 2.6 cm (range, 1.4-3.7 cm), and mean horizontal distance from SN to LBA at 5 cm above SAI was 0.9 cm (range, 0.4-1.8 cm). Conclusion: The variation in SN course observed in our study allowed us to propose “safe zones” for several surgical approaches including the extensile lateral approach to the calcaneus (ELAC), the sinus tarsi approach (STA), the direct lateral approach to the lateral malleolus (DLA), and the posterolateral approach to the ankle (PLA), which we hope will minimize iatrogenic injury to the SN. Level of Evidence: Level IV, case series.
Small RNA sequencing reveals various microRNAs involved in piperine biosynthesis in black pepper (Piper nigrum L.)
Authors: Ding Yuanhao , Mao Yuyuan , Cen Yi , Hu Lisong , Su Yuefeng , Ma Xuemin , Long Lu , Hu Haiyan , Hao Chaoyun , Luo Jie 
Published: November 2021

Abstract
Background
Black pepper (Piper nigrum L.), an important and long-cultivated spice crop, is native to South India and grown in the tropics. Piperine is the main pungent and bioactive alkaloid in the berries of black pepper, but the molecular mechanism for piperine biosynthesis has not been determined. MicroRNAs (miRNAs), which are classical endogenous noncoding small RNAs, play important roles in regulating secondary metabolism in many species, but less is known regarding black pepper or piperine biosynthesis.

Results
To dissect the functions of miRNAs in secondary metabolism especially in piperine biosynthesis, 110 known miRNAs, 18 novel miRNAs and 1007 individual targets were identified from different tissues of black pepper by small RNA sequencing. qRT-PCR and 5′-RLM-RACE experiments were conducted to validate the reliability of the sequencing data and predicted targets. We found 3 miRNAs along with their targets including miR166-4CL, miR396-PER and miR397-CCR modules that are involved in piperine biosynthesis.

Conclusion
MiRNA regulation of secondary metabolism is a common phenomenon in plants. Our study revealed new miRNAs that regulate piperine biosynthesis, which are special alkaloids in the piper genus, and they might be useful for future piperine genetic improvement of black pepper.
Expectant management of prolonged hemolysis following complete transcatheter coil closure of a patent ductus arteriosus after previous pulmonary artery banding: a case report
Authors: Hwang Mao-Sheng , Kuo Ching-Chia , Chung Hung-Tao , Hsu Hsin-Mao , Chu Jaw-Ji , Wang Chao-Jan 
Published: November 2021

Abstract
Background
Transcatheter coil occlusion has been the treatment of choice for closure of small patent ductus arteriosus (PDA). In spite of its safety, complications such as hemolysis still occasionally occur. And the hemolysis almost always occurs following partial transcatheter closure of PDA; hence, it occurs extremely rarely following complete transcatheter closure of PDA without residual ductal flow.

Case presentation
Here, we describe a male newborn who developed prolonged hemolysis following complete transcatheter coil closure of his PDA after previous palliative pulmonary artery banding. Over the following days, we corrected his refractory anemia by repeated blood transfusion with packed red blood cells and frequently monitored his hemoglobin, serum total bilirubin, and serum lactate dehydrogenase. We speculated that the high-velocity pulmonary blood flow jet coming into contact with the extruded part of the coil led to red blood cell mechanical injury, thereby resulting in the hemolysis. We adopted expectant management in expectation of the endothelialization of the coil with a resultant reduction in the hemolysis. The hemolysis, as expected, was reduced gradually until it spontaneously resolved 81 days after coil implantation.

Conclusions
This case reminds us that hemolysis can still potentially occur following complete transcatheter coil closure of PDA. It also highlights the importance of preventing coils from extruding into the pulmonary artery in patients after previous pulmonary artery banding.
Proteinuria is independently associated with carotid atherosclerosis: a multicentric study
Authors: Jiang Wencai , Chen Meixiang , Huang Jianyu , Shang Yu , Qin Changyu , Ruan Zheng , Li Shuang , Wang Ruixin , Li Pengfei , Huang Yuekang , Liu Jianxiong , Xu Lin 
Published: November 2021

Abstract
Background and aims
Atherosclerosis is a vital cause of cardiovascular diseases. The correlation between proteinuria and atherosclerosis, however, has not been confirmed. This study aimed to assess whether there is a relationship between proteinuria and atherosclerosis.

Methods
From January 2016 to September 2020, 13,545 asymptomatic subjects from four centres in southern China underwent dipstick proteinuria testing and carotid atherosclerosis examination. Data on demography and past medical history were collected, and laboratory examinations were performed. The samples consisted of 7405 subjects (4875 males and 2530 females), excluding subjects failing to reach predefined standards and containing enough information. A multivariate logistic regression model was used to adjust the influence of traditional risk factors for atherosclerosis on the results.

Results
Compared with proteinuria-negative subjects, proteinuria-positive subjects had a higher prevalence rate of carotid atherosclerosis. The differences were statistically significant (22.6% vs. 26.7%, χ2 = 10.03, p = 0.002). After adjusting for common risk factors for atherosclerosis, age, sex, BMI, blood lipids, blood pressure, renal function, hypertensive disease, diabetes mellitus and hyperlipidaemia, proteinuria was an independent risk factor for atherosclerosis (OR = 1.191, 95% CI 1.015–1.398, p = 0.033). The Hosmer–Lemeshow test was used to test the risk prediction model of atherosclerosis, and the results showed that the model has high goodness of fit and strong independent variable prediction ability.

Conclusions
Proteinuria is independently related to carotid atherosclerosis. With the increase in proteinuria level, the risk of carotid atherosclerotic plaque increases. For patients with positive proteinuria, further examination of atherosclerosis should not be ignored.
Factors influencing caregiver burden by dementia severity based on an online database from Seoul dementia management project in Korea
Authors: Kim Boyoung , Kim Jennifer Ivy , Na Hae Ri , Lee Kang Sook , Chae Kyung-hee , Kim Sukil 
Published: November 2021

Abstract
Backgrounds
As the prevalence of dementia rises, caregiver burden also increases in South Korea, especially for informal family caregivers. This study aimed to analyze factors affecting caregiver burden by the severity of dementia based on data of patients in Seoul.

Methods
A total of 12,292 individuals aged ≥65 years enrolled in the Seoul Dementia Management Project from 2010 to 2016 in an online database were selected. Caregiver’s burden was assessed using the Korea version of Zarit Burden Interview. Multiple regression analyses were performed to determine factors associated with primary caregiver’s burden after stratifying the severity of dementia.

Results
Most patients showed moderate levels of cognitive impairment (49.4%), behavior problems (82.6%), and ADL dependency (73.6%). After stratifying the severity of dementia, caregivers caring for patients with mild symptoms of dementia were experienced with higher caregiver burden if patients were under a lower score of IADL. Significant factors for caregiver burden among caregivers supporting patients with moderate symptoms of dementia include caregivers’ residence with patients, subjective health status, and co-work with secondary caregivers. Lastly, caregivers for patients with severe dementia symptoms experienced a higher caregiver burden from limited cognitive function, problematic behavior, and caregivers’ negative health status.

Conclusion
In terms of sample size, this study had far more patients than any other domestic or international study. It was meaningful in that it analyzed characteristics of patients with dementia and caregivers affecting the burden of caregivers in Korea. Intensive social supports with multiple coping strategies focusing on different levels of patients’ clinical symptoms and caregivers’ needs should be planned to relieve the caregiver burden.