bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new mechanism for a familiar mutation – bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement
Authors: Fink Tania , Lopdell Thomas J. , Tiplady Kathryn , Handley Renee , Johnson Thomas J. J. , Spelman Richard J. , Davis Stephen R. , Snell Russell G. , Littlejohn Mathew D. 
Published: August 2020

Abstract
Background
The DGAT1 gene encodes an enzyme responsible for catalysing the terminal reaction in mammary triglyceride synthesis, and underpins a well-known pleiotropic quantitative trait locus (QTL) with a large influence on milk composition phenotypes. Since first described over 15 years ago, a protein-coding variant K232A has been assumed as the causative variant underlying these effects, following in-vitro studies that demonstrated differing levels of triglyceride synthesis between the two protein isoforms.

Results
We used a large RNAseq dataset to re-examine the underlying mechanisms of this large milk production QTL, and hereby report novel expression-based functions of the chr14 g.1802265AA > GC variant that encodes the DGAT1 K232A substitution. Using expression QTL (eQTL) mapping, we demonstrate a highly-significant mammary eQTL for DGAT1, where the K232A mutation appears as one of the top associated variants for this effect. By conducting in vitro expression and splicing experiments in bovine mammary cell culture, we further show modulation of splicing efficiency by this mutation, likely through disruption of an exon splice enhancer as a consequence of the allele encoding the 232A variant.

Conclusions
The relative contributions of the enzymatic and transcription-based mechanisms now attributed to K232A remain unclear; however, these results suggest that transcriptional impacts contribute to the diversity of lactation effects observed at the DGAT1 locus.
Comparative transcriptome analysis provides insight into regulation pathways and temporal and spatial expression characteristics of grapevine (Vitis vinifera) dormant buds in different nodes
Authors: Shangguan Lingfei , Chen Mengxia , Fang Xiang , Xie Zhenqiang , Gong Peijie , Huang Yuxiang , Wang Zicheng , Fang Jinggui 
Published: August 2020

AbstractBackgroundBud dormancy is a strategic mechanism plants developed as an adaptation to unfavorable environments. The grapevine (Vitis vinifera) is one of the most ancient fruit vine species and vines are planted all over the world due to their great economic benefits. To better understand the molecular mechanisms underlying bud dormancy between adjacent months, the transcriptomes of ‘Rosario Bianco’ grape buds of 6 months and three nodes were analyzed using RNA-sequencing technology and pair-wise comparison. From November to April of the following year, pairwise comparisons were conducted between adjacent months.ResultsA total of 11,647 differentially expressed genes (DEGs) were obtained from five comparisons. According to the results of cluster analysis of the DEG profiles and the climatic status of the sampling period, the 6 months were divided into three key processes (November to January, January to March, and March to April). Pair-wise comparisons of DEG profiles of adjacent months and three main dormancy processes showed that the whole grapevine bud dormancy period was mainly regulated by the antioxidant system, secondary metabolism, cell cycle and division, cell wall metabolism, and carbohydrates metabolism. Additionally, several DEGs, such asVvGA2OX6andVvSS3, showed temporally and spatially differential expression patterns, which normalized to a similar trend during or before April.ConclusionConsidering these results, the molecular mechanisms underlying bud dormancy in the grapevine can be hypothesized, which lays the foundation for further research.
Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report
Authors: Faqihi Fahad , Alharthy Abdulrahman , Alshaya Rayan , Papanikolaou John , Kutsogiannis Demetrios J. , Brindley Peter G. , Karakitsos Dimitrios 
Published: August 2020

Abstract
Background
Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE).

Case presentation
A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition.

Conclusion
Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.
Anti-modified citrullinated vimentin antibody: a novel biomarker associated with cardiac systolic dysfunction in patients with rheumatoid arthritis
Authors: Norouzi Somayye , Javinani Ali , Aminorroaya Arya , Masoumi Maryam 
Published: August 2020

Abstract
Background
Studies have demonstrated that seropositive patients with rheumatoid arthritis (RA) are susceptible to cardiovascular diseases (CVDs). In this study, we aimed to determine the association of autoantibodies with the echocardiographic parameters of systolic and diastolic dysfunction in such patients.

Methods
In this cross-sectional study, we evaluated patients with RA who were referred to our clinic from October 2017 to August 2018. After the exclusion of patients with concomitant CVD, all patients underwent transthoracic echocardiography and measurement of plasma autoantibodies. Moreover, possible confounders—including medications, CVD risk factors, Framingham risk score, disease activity score-28, duration of disease, simple disease activity index, and functional status—were assessed.

Results
We studied 135 patients with RA (mean age = 52.3 years; 111 (82.2%) females). We had missing data rates of up to 8.9% for some characteristics. E velocity was inversely correlated with rheumatoid factor (P = 0.009). Furthermore, the plasma levels of anti-citrullinated protein and anti-modified citrullinated vimentin (anti-MCV) antibodies were negatively correlated with left ventricular ejection fraction (LVEF) (P = 0.019 and P<0.001, respectively). After an adjustment for possible confounders, the linear regression model demonstrated that the anti-MCV level and the patient’s age are significant predictors of LVEF. The receiver operating characteristic curve showed that anti-MCV antibody titer≥547.5 (IU/mL) signifies reduced LVEF (<50%) with a sensitivity of 85.7% and specificity of 93% (C-statistic = 0.843).

Conclusions
Our findings showed a significant inverse correlation between anti-MCV antibody titer and LVEF. These results indicate that the application of anti-MCV is promising for the screening and early detection of cardiac systolic dysfunction. Future prospective studies will determine its role.
Time-to-reperfusion in patients with acute myocardial infarction and mortality in prehospital emergency care: meta-analysis
Authors: Fu Xing , Wilson Philip , Chung Wing Sun Faith 
Published: August 2020

Abstract
Background
People living in rural areas usually suffer comparatively disadvantaged emergency health care than those living in urban areas, reasons including long transit time due to geographic factors. As for many time critical diseases, it is necessary to obtain treatment as quickly as possible.

Methods
Screening of eligible studies were conducted based on inclusion an exclusion criteria. A comprehensive search was conducted by using following database: EMBASE, Medline, Cochrane library and Scopus. Quality assessment tool for observational cohort and cross-sectional study is used for assessing the risk of bias. The time group were defined based on the median or mean transit time among patients. In symptom onset-balloon time, we take 120 min transit time as the standard so patients in included studies are divided into two groups:less than 120 min (group A) and more than 120 min (group B). The collected data were used for quantitative analysis, they were inputted into Review Manager Software (v5.3) to produce summary results.

Results
Ten studies representing 71,099 patients were included in the meta-analysis. All studies were retrospective and prospective observational studies and RCTs in which patients experienced ST-elevation myocardial infarction (STEMI) and were treated with percutaneous coronary intervention (PCI). Random effects meta-analysis of the point estimate was 0.69 (CI 0.60, 0.79). Heterogeneity between study results was evaluated via examination of the forest plots and quantified by using I2 statistic. Heterogeneity in two stage time was moderate among studies (I2 = 29%, P = 0.23).

Conclusion
The meta-analysis for included studies report less mortality in less than 120 min symptom onset-balloon and door-balloon time than that in more than 120 min. It is necessary to optimize the prehospital system for rapid decision making and logical destination and mode of transport with prehospital notification of the cath lab so that the hospital is ready to optimize door to balloon time.
Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled
Authors: Shook Lydia L. , Shui Jessica E. , Boatin Adeline A. , Devane Samantha , Croul Natalie , Yonker Lael M. , Matute Juan D. , Lima Rosiane S. , Schwinn Muriel , Cvrk Dana , Gardner Laurel , Azevedo Robin , Stanton Suzanne , Bordt Evan A. , Yockey Laura J. , Fasano Alessio , Li Jonathan Z. , Yu Xu G. , Kaimal Anjali J. , Lerou Paul H. , Edlow Andrea G. 
Published: August 2020

Abstract
Background
Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them.

Methods
A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH). The first SARS-CoV-2 positive pregnant woman was enrolled on April 2, and enrollment was expanded to SARS-CoV-2 negative controls on April 20. A unified enrollment strategy with a single consent process for pregnant women and newborns was implemented on May 4. SARS-CoV-2 status was determined by viral detection on RT-PCR of a nasopharyngeal swab. Wide-ranging and pregnancy-specific samples were collected from maternal participants during pregnancy and postpartum. Newborn samples were collected during the initial hospitalization.

Results
Between April 2 and June 9, 100 women and 78 newborns were enrolled in the MGH COVID-19 biorepository. The rate of dyad enrollment and number of samples collected per woman significantly increased after changes to enrollment strategy (from 5 to over 8 dyads/week, P < 0.0001, and from 7 to 9 samples, P < 0.01). The number of samples collected per woman was higher in SARS-CoV-2 negative than positive women (9 vs 7 samples, P = 0.0007). The highest sample yield was for placenta (96%), umbilical cord blood (93%), urine (99%), and maternal blood (91%). The lowest-yield sample types were maternal stool (30%) and breastmilk (22%). Of the 61 delivered women who also enrolled their newborns, fewer women agreed to neonatal blood compared to cord blood (39 vs 58, P < 0.0001).

Conclusions
Establishing a COVID-19 perinatal biorepository required patient advocacy, transdisciplinary collaboration and creative solutions to unique challenges. This biorepository is unique in its comprehensive sample collection and the inclusion of a control population. It serves as an important resource for research into the impact of COVID-19 on pregnant women and newborns and provides lessons for future biorepository efforts.
Discriminative validity of the Core outcome set functional independence in a population of older adults
Authors: Dockx Yvonne J. C. , Molenaar Esther A. L. M. , Barten Di-Janne J. A. , Veenhof Cindy 
Published: August 2020

Abstract
Background
Clinicians are currently challenged to support older adults to maintain a certain level of Functional Independence (FI). FI is defined as “functioning physically safely and independent from another person, within one’s own context”. A Core Outcome Set was developed to measure FI. The purpose of this study was to assess discriminative validity of the Core Outcome Set FI (COSFI) in a population of Dutch older adults (≥ 65 years) with different levels of FI. Secondary objective was to assess to what extent the underlying domains ‘coping’, ‘empowerment’ and ‘health literacy’ contribute to the COSFI in addition to the domain ‘physical capacity’.

Methods
A population of 200 community-dwelling older adults and older adults living in residential care facilities were evaluated by the COSFI. The COSFI contains measurements on the four domains of FI: physical capacity, coping, empowerment and health literacy. In line with the COSMIN Study Design checklist for Patient-reported outcome measurement instruments, predefined hypotheses regarding prediction accuracy and differences between three subgroups of FI were tested. Testing included ordinal logistic regression analysis, with main outcome prediction accuracy of the COSFI on a proxy indicator for FI.

Results
Overall, the prediction accuracy of the COSFI was 68%. For older adults living at home and depending on help in (i)ADL, prediction accuracy was 58%. 60% of the preset hypotheses were confirmed. Only physical capacity measured with Short Physical Performance Battery was significantly associated with group membership. Adding health literacy with coping or empowerment to a model with physical capacity improved the model significantly (p < 0.01).

Conclusions
The current composition of the COSFI, did not yet meet the COSMIN criteria for discriminative validity. However, with some adjustments, the COSFI potentially becomes a valuable instrument for clinical practice. Context-related factors, like the presence of a spouse, also may be a determining factor in this population. It is recommended to include context-related factors in further research on determining FI in subgroups of older people.
Determinants of overburdening among informal carers: a systematic review
Authors: Lindt Nienke , van Berkel Jantien , Mulder Bob C. 
Published: August 2020

Abstract
Background
The world’s population is ageing, resulting in rising care demands and healthcare costs, which in turn lead to a shift from formal to informal care. However, not only is the number of potential informal carers fast decreasing, but also informal caregivers are experiencing a higher caregiver burden. This literature review aims to synthesize the literature on the common determinants of caregiver burden in Western countries, to help ensure future continuation of informal care in the home context, and to improve or sustain the quality of life of caregivers and patients alike.

Method
A systematic review of peer-reviewed articles included in PubMed, Scopus, and/or PsychInfo was conducted.

Results
Seventeen articles were included. The most important predictors were the duration of caregiving and the patient’s dependency level, in terms of both physical and mental dependency stemming from decreased cognitive capacity or behavioural problems. Some specific illnesses and role conflicts or captivity also increased caregiver burden, whereas social support lowered it. Being a female caregiver or having an adult–child relationship led to a higher burden.

Conclusions
The most important predictors of caregiver burden are the duration of caregiving and the patient’s dependency level. In addition, the patient’s behavioural problems and cognitive capacity determine dependency level, and thus care burden. Interventions to relieve burden need to be adapted to the illness trajectory of specific diseases and corresponding needs for social support for both the recipient and the caregiver. Changing role expectations, leading to men being more involved, could reduce the disproportionately high burden for women.
Effectiveness of an online education intervention on stress and coping of family members after placing a relative with dementia into a residential care facility: protocol of a randomised controlled trial
Authors: Hui Zhaozhao , Yang Chen , Li Jieqiong , Lee Diana Tze Fan 
Published: August 2020

Abstract
Background
After residential care placement, family members may be exposed to stressors like difficulty in role changes, interpersonal conflict with facility staff, and emotional torment. These can threaten family members’ own health and well-being and even influence the extent they involve in their relative’s care. This study aims to evaluate an online education intervention for Chinese family members whose relatives with dementia have been placed into a residential care facility.

Methods
This protocol describes a two-arm randomised controlled trial. A total of 150 family members of residents with dementia will be recruited from four to six residential care facilities in Xi’an, Shaanxi, China and randomly allocated to either the intervention or control group. Family members in the intervention group will receive a six-week group-based online education intervention, while those in the control group will receive routine care. Family members’ stress, coping, caregiving burden, and family involvement, as well as their relative’s behavioural and psychological symptoms of dementia will be assessed at immediately post-intervention and six-week follow-up. Effectiveness of the intervention will be analysed by generalised estimating equation model, based on the intention-to-treat principle. A process evaluation of the intervention will also be undertaken.

Discussion
This study will be of great significance in addressing family members’ stressors after institutionalising a relative with dementia and promoting the implementation of family-centred care in practice especially in residential care facilities.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1900024582, Registered 18 July 2019.
Care of family caregivers of persons with dementia (CaFCa) through a tailor-made mobile app: study protocol of a complex intervention study
Authors: Kabir Zarina Nahar , Leung Angela Yee Man , Grundberg Åke , Boström Anne-Marie , Lämås Kristina , Kallström Ana Paula , Moberg Cecilia , Cronfalk Berit Seiger , Meijer Sebastiaan , Konradsen Hanne 
Published: August 2020

Abstract
Background
Globally, family members account for the main source of caregiving of persons with dementia living at home. Providing care to family members with dementia often has negative health consequences for caregivers such as stress, depression and low quality of life. Yet, formal support for family caregivers (FCs) is limited. Telehealth technology has the potential to provide health care and social support to FCs. This study aims to assess the effectiveness of providing support by healthcare professionals (HPs) through a mobile app in reducing stress, depressive symptoms and loneliness, and improving mental health and quality of life of FCs of persons with dementia.

Methods
Using a pragmatic intervention design, this study will use pre- and post-intervention assessment to evaluate the effectiveness of the proposed intervention in a sample of 78 FCs of persons with dementia (PWD). The intervention will be implemented by approximately 5 HPs specialized in dementia care based in the municipalities in Sweden. The main thrust of the intervention is to provide professional support, with help of an interactive mobile app, to family members in their caregiving role for PWDs. Qualitative interviews with HPs and FCs form the groundwork of the development of the mobile app. By using the app on smart phone or tablet, the FC, in groups of 8–10, will communicate with peers and a HP exchanging ideas on how to deal with PWD’s behavioral and cognitive changes and get support. They will also be able to discuss stressful events and access mindfulness exercises focused on themselves. Quantitative data will be collected before and at three time points after the 8-week intervention to assess changes in the health outcomes of the FCs. In-depth interviews will be conducted after the intervention to capture the experiences of FCs and HPs regarding the ease of use and acceptability of the app.

Discussion
This tailor-made mobile app has the high potential to be a practical platform for supporting FCs to alleviate stress and improve mental health irrespective of distance to the nearest health care or social service center.

Trial registration
ISRCTN, ISRCTN46137262. Registered 10 October 2019.