bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis
Authors: Gerstner Christina , Turcinov Sara , Hensvold Aase H. , Chemin Karine , Uchtenhagen Hannes , Ramwadhdoebe Tamara H. , Dubnovitsky Anatoly , Kozhukh Genadiy , Rönnblom Lars , Kwok William W. , Achour Adnane , Catrina Anca I. , van Baarsen Lisa G. M. , Malmström Vivianne 
Published: May 2020

Abstract
Background
HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder for which many autoantigens have been described.

Results
Using multi-parameter flow cytometry, we developed a multi-HLA class II tetramer approach to simultaneously study several antigen specificities in RA patient samples. We focused on previously described citrullinated HLA-DRB1*04:01-restricted T cell epitopes from α-enolase, fibrinogen-β, vimentin as well as cartilage intermediate layer protein (CILP). First, we examined inter-assay variability and the sensitivity of the assay in peripheral blood from healthy donors (n = 7). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws (n = 14). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia (n = 5) and early RA patients (n = 5) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients (n = 10) and found that the group of patients achieving minimum disease activity (DAS28 < 2.6) at 6 months follow-up displayed a decrease in the frequency of citrulline-specific T cells.

Conclusions
Our study demonstrates the development of a sensitive tetramer panel allowing simultaneous characterisation of antigen-specific T cells in ex vivo patient samples including RA ‘at risk’ subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens.
Comparison of bioresorbable vs durable polymer drug-eluting stents in unprotected left main (from the RAIN-CARDIOGROUP VII Study)
Authors: Iannaccone Mario , Barbero Umberto , De Benedictis Michele , Imori Yoichi , Quadri Giorgio , Trabattoni Daniela , Ryan Nicola , Venuti Giuseppe , Montabone Andrea , Wojakowski Wojciech , Rognoni Andrea , Helft Gerard , Parma Radoslaw , De Luca Leonardo , Autelli Michele , Boccuzzi Giacomo , Mattesini Alessio , Templin Christian , Cerrato Enrico , Wańha Wojciech , Smolka Grzegorz , Huczek Zenon , Tomassini Francesco , Cortese Bernardo , Capodanno Davide , Chieffo Alaide , Nuñez-Gil Ivan , Gili Sebastiano , Bassignana Antonia , di Mario Carlo , Doronzo Baldassarre , Omedè Pierluigi , D’Amico Maurizio , Tedeschi Delio , Varbella Ferdinando , Luscher Thomas , Sheiban Imad , Escaned Javier , Rinaldi Mauro , D’Ascenzo Fabrizio 
Published: May 2020

Abstract
Background
There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations.

Methods
In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 μm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed.

Results
From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12–22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES.

Conclusion
In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events.

Trial registration
ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.
Relation between quantity and quality of peri-coronary epicardial adipose tissue and its underlying hemodynamically significant coronary stenosis
Authors: Du Yu , Yang Lin , Liu Yan , Yang Bangguo , Lv Sai , Hu Chenping , Zhu Yong , Zhang Hongkai , Ma Qian , Wang Zhijian , Liu Yuyang , Shi Dongmei , Zhao Yingxin , Xu Lei , Zhou Yujie 
Published: May 2020

Abstract
Background
We aimed to investigate the association of lesion-specific epicardial adipose tissue (EAT) volume and density with the presence of myocardial ischemia.

Methods
We enrolled 45 patients (55 lesions) with known or suspected coronary artery disease who underwent coronary computed tomography angiography (CTA) followed by invasive fractional flow reserve (FFR) assessment within 30 days. EAT volume (index) and density in patient-, vessel- and lesion-level were measured on CTA images. Lesion-specific ischemia was defined as a lesion with stenosis diameter > 90% or FFR ≤0.80. Multivariate analysis determined the independent association of EAT parameters with lesion-specific ischemia.

Results
Mean age of the patients was 60 years, and 75% were male. Overall, 55.6% of patients had ischemic lesions and a mean FFR baseline value of 0.82 ± 0.10. Total EAT volume index was significantly higher in patients with functionally or anatomically significant stenosis. Specifically, peri-lesion EAT volume index, not the density, was positively correlated with lesion-specific ischemia independent of luminal stenosis and plaque characteristics (hazard ratio 1.56, 95% confidence interval 1.04–2.33, P = 0.032; per 0.1 ml/m2 increase). Moreover, peri-lesion EAT volume was negatively correlated with lesion FFR values, whereas total EAT volume was positively correlated with fat accumulation and glucose metabolism. In addition, there was no association of EAT volume or density with myocardial ischemia in vessel-level analysis.

Conclusions
Lesion-specific EAT volume index, but not density, seems positively and independently associated with myocardial ischemia, while its incremental diagnostic value of lesion-specific ischemia should be further investigated.
Preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with major adverse cardiovascular and cerebrovascular events in coronary heart disease patients undergoing non-cardiac surgery
Authors: Larmann Jan , Handke Jessica , Scholz Anna S. , Dehne Sarah , Arens Christoph , Gillmann Hans-Jörg , Uhle Florian , Motsch Johann , Weigand Markus A. , Janssen Henrike 
Published: May 2020

Abstract
Background
Preoperative risk prediction in patients at elevated cardiovascular risk shows limited accuracy. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) indicate systemic inflammation. Both have been investigated for outcome prediction in the field of oncology and cardiovascular medicine, as well as risk prediction of adverse cardiovascular events in non-surgical patients at increased cardiovascular risk.

Methods
For this post-hoc analysis, we included all 38 coronary heart disease patients from the Leukocytes and Cardiovascular Perioperative Events cohort-1 study scheduled for elective non-cardiac surgery. We evaluated preoperative differential blood counts for association with major adverse cardiovascular and cerebrovascular events (MACCE) defined as the composite endpoint of death, myocardial ischemia, myocardial infarction, myocardial injury after non-cardiac surgery, or embolic or thrombotic stroke within 30 days after surgery. We used Youden’s index to calculate cut-off values for PLR and NLR. Additive risk-predictive values were assessed using receiver operating characteristic curve and net reclassification (NRI) improvement analyses.

Results
Patients with the composite endpoint MACCE had higher PLR and NLR (309 [206; 380] vs. 160 [132; 203], p = 0.001; 4.9 [3.5; 8.1] vs. 2.6 [2.2; 3.4]), p = 0.001). Calculated cut-offs for PLR > 204.4 and NLR > 3.1 were associated with increased risk of 30-day MACCE (OR 7, 95% CI [1.2; 44.7], p = 0.034; OR 36, 95% CI [1.8; 686.6], p = 0.001). Furthermore, NLR improved risk prediction in coronary heart disease patients undergoing non-cardiac surgery when combined with hs-cTnT or NT-proBNP (NRI total = 0.23, p = 0.008, NRI total = 0.26, p = 0.005).

Conclusions
Both PLR and NLR were associated with perioperative cardiovascular adverse events in coronary heart disease patients. NLR proved to be of additional value for preoperative risk stratification. Both PLR and NLR could be used as inexpensive and broadly available tools for perioperative risk assessment.

Trial registration
NCT02874508, August 22, 2016.
Sex and gender differences in technology needs and preferences among informal caregivers of persons with dementia
Authors: Xiong Chen , Ye Bing , Mihailidis Alex , Cameron Jill I. , Astell Arlene , Nalder Emily , Colantonio Angela 
Published: May 2020

Abstract
Background
Dementia is a major public health concern associated with significant caregiver demands and there are technologies available to assist with caregiving. However, there is a paucity of information on caregiver needs and preferences for these technologies, particularly from a sex and gender perspective. To address this gap in research, the objectives of this study are to examine (1) the knowledge of technology, (2) perceived usefulness of technology, (3) feature preferences when installing and using technology and (4) sex and gender influences on technology needs and preferences among family caregivers of persons with dementia (PWD) across North America.

Methods
A secondary analysis was conducted on an existing cross-sectional survey with family caregivers of PWDs. Respondents were recruited through the Alzheimer Society of Canada, the Victorian Order of Nurses and Adult Day Programs and other Canadian health care provision institutes. Descriptive statistics, bivariate and multivariate analyses were used to describe the study sample, uncover differences between male and female caregivers and examine sex and gender influences on caregivers’ technology needs and preferences.

Results
A total of 381 eligible responses were received over a nine month data collection period. The majority of respondents did not know much about and never used any technologies to assist with caregiving. “Being easy to install”, “easy to learn how to use” and “cost” were identified as the most important features when purchasing and setting up technology, while “reliability” was identified as the most important feature when using technology. Most respondents were willing to pay up to $500 to acquire individual technologies. Controlling for other socio-demographic variables, female respondents were more likely to have some or more knowledge about technology for caregiving while male respondents were more willing to pay higher amounts for these technologies compared to their female counterparts.

Conclusions
As one of the first studies of its kind, our findings represent a step towards the incorporation of sex and gender considerations such as cost and reliability in technology design and promotion for caregivers. Future efforts are warranted to establish an in-depth understanding of sex and gender influences in relation to other social and environmental factors.
Enabling routine β-thalassemia Prevention and Patient Management by scalable, combined Thalassemia and Hemochromatosis Mutation Analysis
Authors: Hashmi Ghazala , Qidwai Asim , Fernandez Kristopher , Seul Michael 
Published: May 2020

Abstract
Background
Beta (β)-thalassemia is one of the most common inherited disorders worldwide, with high prevalence in the Mediterranean, the Middle East and South Asia. Over the past 40 years, awareness and prevention campaigns in many countries have greatly reduced the incidence of affected child births. In contrast, much remains to be done in South-Asia. Thus, for Pakistan, an estimated ~ 7000 children annually are born with thalassemia, with no sign of improvement. Although there is good agreement that intermarriage of carriers significantly contributes to the high prevalence of the disorder, effective tools for molecular screening and diagnosis on which to base prevention programs are not readily available.

Methods
Here, we present results for a novel LeanSequencing™ process to identify a combination of 18 β-thalassemia mutations (including the sickle cell anemia mutation, HbS, and structural variants HbC and HbE) and 2 hemochromatosis mutations in a multi-ethnic population of 274 pediatric and adolescent patients treated at Afzaal Memorial Thalassemia Foundation in Karachi, Pakistan.

Results
We found substantial differences in the predominance of disease-causing mutations among the principal ethnic groups in our cohort. We also found the hemochromatosis mutation H63D C > G in 61 (or 22.1%) of our patients including 6 (or 2.2%) homozygotes.

Conclusions
To our knowledge, this is the first screen combining a large set of β-thalassemia and hemochromatosis mutations, so as to facilitate the early identification of patients who may be at increased potential risk for complications from iron overload and thereby to improve the prospective management of thalassemia patients.
Quantitative phenotype scan statistic (QPSS) reveals rare variant associations with Alzheimer’s disease endophenotypes
Authors: Katsumata Yuriko , Fardo David W. 
Published: May 2020

Abstract
Background
Current sequencing technologies have provided for a more comprehensive genome-wide assessment and have increased genotyping accuracy of rare variants. Scan statistic approaches have previously been adapted to genetic sequencing data. Unlike currently-employed association tests, scan-statistic-based approaches can both localize clusters of disease-related variants and, subsequently, examine the phenotype association within the resulting cluster. In this study, we present a novel Quantitative Phenotype Scan Statistic (QPSS) that extends an approach for dichotomous phenotypes to continuous outcomes in order to identify genomic regions where rare quantitative-phenotype-associated variants cluster.

Results
We demonstrate the performance and practicality of QPSS with extensive simulations and an application to a whole-genome sequencing (WGS) study of cerebrospinal fluid (CSF) biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Using QPSS, we identify regions of rare variant enrichment associated with levels of AD-related proteins, CSF Aβ1–42 and p-tau181P.

Conclusions
QPSS is implemented under the assumption that causal variants within a window have the same direction of effect. Typical self-contained tests employ a null hypothesis of no association between the target variant set and the phenotype. Therefore, an advantage of the proposed competitive test is that it is possible to refine a known region of interest to localize disease-associated clusters. The definition of clusters can be easily adapted based on variant function or annotation.
Prevalence and correlates of job and insurance problems among young breast cancer survivors within 18 months of diagnosis
Authors: Naughton Michelle J. , Beverly Hery Chloe M. , Janse Sarah A. , Naftalis Elizabeth Z. , Paskett Electra D. , Van Zee Kimberly J. 
Published: May 2020

Abstract
Background
The prevalence and correlates of job and insurance problems were examined among a cohort of young U.S. breast cancer survivors during the first 18-months following diagnosis.

Methods
Participants were 708 women diagnosed at ≤45 years with stage I-III breast cancer. 90% were non-Hispanic white, 76% were married/partnered and 67% had ≥4-year college degree. Univariable and multivariable logistic regression examined the associations between demographic, lifestyle and clinical factors with job and insurance problems.

Results
18-months after diagnosis, 56% of participants worked full-time, 16% part-time, 18% were homemakers and/or students, 4.5% were unemployed, and 2.4% were disabled. The majority (86%) had private insurance. Job-related problems were reported by 40% of women, and included believing they could not change jobs for fear of losing health insurance (35.0%), being fired (2.3%), and being demoted, denied promotion or denied wage increases (7.8%). Greater job-related problems were associated with being overweight vs. under/normal weight (p = 0.006), income <$50,000/per year (p = 0.01), and working full-time vs. part-time (p = 0.003). Insurance problems were reported by 27% of women, and included being denied health insurance (2.6%), health insurance increases (4.3%), being denied health benefit payments (14.8%) or denied life insurance (11.4%). Insurance problems were associated with being under/normal weight vs. obese (p = 0.01), not being on hormone therapy (p < 0.001), and a tumor size > 5 cm vs. < 2 cm (p = 0.01).

Conclusions
Young survivors experienced significant job- and insurance-related issues following diagnosis. To the extent possible, work and insurance concerns should be addressed prior to treatment to inform work expectations and avoid unnecessary insurance difficulties.
Effect of feeding mode on infant growth and cognitive function: study protocol of the Chilean infant Nutrition randomized controlled Trial (ChiNuT)
Authors: Toro-Campos Rosario , Algarín Cecilia , Peirano Patricio , Peña Marcela , Murguia-Peniche Teresa , Wu Steven S. , Uauy Ricardo 
Published: May 2020

Abstract
Background
A central aim for pediatric nutrition is to develop infant formula compositionally closer to human milk. Milk fat globule membranes (MFGM) have shown to have functional components that are found in human milk, suggesting that addition of bovine sources of MFGM (bMFGM) to infant formula may promote beneficial outcomes potentially helping to narrow the gap between infants who receive human breast milk or infant formula. The objective of the current study is to determine how the addition of bMFGM in infant formula and consumption in early infancy affects physical growth and brain development when compared to infants fed with a standard formula and a reference group of infants fed with mother’s own milk.

Methods
Single center, double-blind, and parallel randomized controlled trial. Planned participant enrollment includes: infants exclusively receiving breast milk (n = 200; human milk reference group; HM) and infants whose mothers chose to initiate exclusive infant formula feeding before 4 months of age (n = 340). The latter were randomized to receive one of two study formulas until 12 months of age: 1) cow’s milk based infant formula that had docosahexaenoic (DHA) (17 mg/100 kcal) and arachidonic acid (ARA) (25 mg/100 kcal); 1.9 g protein/100 kcal; 1.2 mg Fe/100 kcal (Standard formula; SF) or 2) a similar infant formula with an added source of bovine MFGM (whey protein-lipid concentrate (Experimental formula; EF). Primary outcomes will be: 1) Physical growth (Body weight, length, and head circumference) at 730 days of age; and 2) Cognitive development (Auditory Event-Related Potential) at 730 days of age. Data will be analyzed for all participants allocated to each study feeding group.

Discussion
The results of this study will complement the knowledge regarding addition of bMFGM in infant formula including support of healthy growth and improvement of neurodevelopmental outcomes.

Trial registration
NCT02626143, registered on December 10th 2015.
Effects of journal therapy counseling with anxious pregnant women on their infants’ sleep quality: a randomized controlled clinical trial
Authors: Montazeri Maryam , Mirghafourvand Mojgan , Esmaeilpour Khalil , Mohammad-Alizadeh-Charandabi Sakineh , Amiri Paria 
Published: May 2020

Abstract
Background
Sleep is especially important for infants, since it stimulates the development of neural connections in their brains. Psychological stress such as anxiety could affect sleep quality. This study investigated the effects of journal therapy counseling sessions on the infants’ sleep quality based on mothers’ perception (primary outcome), maternal anxiety, infants’ anthropometric and developmental parameters, and the frequency of exclusive breastfeeding (secondary outcomes).

Methods
A total of 70 healthy women with gestational age of 28–31 weeks participated in this randomized controlled trial. The participants were randomly allocated into intervention and control groups using randomized block design. Three in-person journal therapy sessions and three telephone counseling sessions (2 between in-person sessions and 1 one month postpartum) were provided to those in the intervention group, while the control group only received routine care. The Infant Sleep Questionnaire (ISQ), Exclusive Breastfeeding Checklist, and Infant Anthropometric Parameters Checklist were completed at two and four months postpartum. The Beck Anxiety Inventory (BAI) was completed during pregnancy, at the end of the intervention, and at two and four months postpartum, and the Ages and Stages Questionnaire (ASQ) was completed at 4 months postpartum. Data were analyzed using chi-square, independent t-test, ANCOVA and repeated measure ANOVA.

Results
There was no significant difference between the two groups in demographic characteristics and baseline anxiety scores. The mean sleep quality score in infants two months of age (MD: -4.2; 95%CI: − 1.1 to − 7.2; P = 0.007) and four months of age (MD: -5.5; 95%CI: − 8.4 to − 2.7; P < 0.001) was significantly lower in the intervention group than that of those in the control group. Based on the repeated measure ANOVA results, the mean postpartum anxiety score of mothers in the intervention group was significantly lower than that of those in the control group (AMD: -7.7; 95%CI: − 5.5 to − 10.1; P < 0.001). There was no significant difference between the two groups regarding other outcomes including the frequency of exclusive breastfeeding, and anthropometric and developmental parameters (P > 0.05).

Conclusion
Journal therapy can decrease mothers’ anxiety and improve the infants’ sleep quality based on their perception. However, further studies are required before drawing any definitive conclusion.

Trial registration number
Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N45. Date of registration: August 11, 2018. URL: https://en.irct.ir/trial/33211.