bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theory-based approach to developing an implementation plan to support the adoption of a patient decision aid for Down syndrome prenatal screening
Authors: Agbadjé Titilayo Tatiana , Menear Matthew , Gagnon Marie-Pierre , Légaré France 
Published: May 2021

Abstract
Background
Our team has developed a decision aid to help pregnant women and their partners make informed decisions about Down syndrome prenatal screening. However, the decision aid is not yet widely available in Quebec’s prenatal care pathways.

Objective
We sought to identify knowledge translation strategies and develop an implementation plan to promote the use of the decision aid in prenatal care services in Quebec, Canada.

Methods
Guided by the Knowledge-to-Action Framework and the Theoretical Domains Framework, we performed a synthesis of our research (11 publications) on prenatal screening in Quebec and on the decision aid. Two authors independently reviewed the 11 articles, extracted information, and mapped it onto the Knowledge-to-Action framework. Using participatory action research methods, we then recruited pregnant women, health professionals, managers of three prenatal care services, and researchers to (a) identify the different clinical pathways followed by pregnant women and (b) select knowledge translation strategies for a clinical implementation plan. Then, based on all the information gathered, the authors established a consensus on strategies to include in the plan.

Results
Our knowledge synthesis showed that pregnant women and their partners are not sufficiently involved in the decision-making process about prenatal screening and that there are numerous barriers and facilitators of the use of the decision aid in clinical practice (e.g., low intention to use it among health providers). Using a participatory action approach, we met with five pregnant women, three managers, and six health professionals. They informed us about three of Quebec’s prenatal care pathways and helped us identify 20 knowledge translation strategies (e.g., nurse discusses decision aid with women before they meet the doctor) to include in a clinical implementation plan. The research team reached a consensus about the clinical plan and also about broader organizational strategies, such as training healthcare providers in the use of the decision aid, monitoring its impact (e.g., measure decisional conflict) and sustaining its use (e.g., engage key stakeholders in the implementation process).

Conclusion
Next steps are to pilot our implementation plan while further identifying global strategies that target institutional, policy, and systemic supports for implementation.
Fast and efficient Rmap assembly using the Bi-labelled de Bruijn graph
Authors: Mukherjee Kingshuk , Rossi Massimiliano , Salmela Leena , Boucher Christina 
Published: May 2021

AbstractGenome wide optical maps are high resolution restriction maps that give a unique numeric representation to a genome. They are produced by assembling hundreds of thousands of single molecule optical maps, which are called Rmaps. Unfortunately, there are very few choices for assembling Rmap data. There exists only one publicly-available non-proprietary method for assembly and one proprietary software that is available via an executable. Furthermore, the publicly-available method, by Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006), follows the overlap-layout-consensus (OLC) paradigm, and therefore, is unable to scale for relatively large genomes. The algorithm behind the proprietary method, Bionano Genomics’ Solve, is largely unknown. In this paper, we extend the definition of bi-labels in the paired de Bruijn graph to the context of optical mapping data, and present the first de Bruijn graph based method for Rmap assembly. We implement our approach, which we refer to as rmapper, and compare its performance against the assembler of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) and Solve by Bionano Genomics on data from three genomes: E. coli, human, and climbing perch fish (Anabas Testudineus). Our method was able to successfully run on all three genomes. The method of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) only successfully ran on E. coli. Moreover, on the human genome rmapper was at least 130 times faster than Bionano Solve, used five times less memory and produced the highest genome fraction with zero mis-assemblies. Our software, rmapper is written in C++ and is publicly available under GNU General Public License at https://github.com/kingufl/Rmapper.
Case report: a step-wise management of concurrent presentation of congenital single lung and aberrant right subclavian artery in an infant girl
Authors: Park Keon Young , Janek Kevin C. , Hermsen Joshua L. , Anagnostopoulos Petros V. , Le Hau D. 
Published: May 2021

Abstract
Introduction
Congenital single lung (CSL) is a rare condition, and symptomatic patients often present with respiratory distress or recurrent respiratory infection due to mediastinal shift causing vascular or airway compression. Aberrant right subclavian artery (ARSA) is another rare congenital anomality that can lead to tracheal or esophageal compressions. There is only one other case of concurrent presentation of CSL and ARSA reported, which presented unique challenge in surgical management of our patient. Here we present a step-wise, multidisciplinary approach to manage symptomatic CSL and ARSA.

Case presentation
An infant girl with a prenatal diagnosis of CSL developed worsening stridor and several episodes of respiratory illnesses at 11 months old. Cross-sectional imaging and bronchoscopic evaluation showed moderate to severe distal tracheomalacia with anterior and posterior tracheal compression resulting from severe mediastinal rotation secondary to right-sided CSL. It was determined that her tracheal compression was mainly caused by her aortic arch wrapping around the trachea, with possible additional posterior compression of the esophagus by the ARSA. She first underwent intrathoracic tissue expander placement, which resulted in immediate improvement of tracheal compression. Two days later, she developed symptoms of dysphagia lusoria due to increased posterior compression of her esophagus by the ARSA. She underwent transposition of ARSA to the right common carotid with immediate resolution of dysphagia lusoria. As the patient grew, additional saline was added to the tissue expander due to recurrence in compressive symptoms.

Conclusions
Concurrent presentation of CSL and ARSA is extremely rare. Asymptomatic CSL and ARSA do not require surgical interventions. However, if symptomatic, it is crucial to involve a multidisciplinary team for surgical planning and to take a step-wise approach as we were able to recognize and address both tracheomalacia and dysphagia lusoria in our patient promptly.
Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down’s syndrome mouse model
Authors: Urbano-Gámez Jesús David , Casañas Juan José , Benito Itziar , Montesinos María Luz 
Published: May 2021

AbstractDown syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.
CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Cui Qingya , Qian Chongsheng , Xu Nan , Kang Liqing , Dai Haiping , Cui Wei , Song Baoquan , Yin Jia , Li Zheng , Zhu Xiaming , Qu Changju , Liu Tianhui , Shen Wenhong , Zhu Mingqing , Yu Lei , Wu Depei , Tang Xiaowen 
Published: May 2021

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.
Increased expression of KPNA2 predicts unfavorable prognosis in ovarian cancer patients, possibly by targeting KIF4A signaling
Authors: Cui Xiangrong , Wang Honghong , Wu Xueqing , Huo Kai , Jing Xuan 
Published: May 2021

Abstract
Background
Karyopherin α-2 (KPNA2) is a member of karyopherin family, which is proved to be responsible for the import or export of cargo proteins. Studies have determined that KPNA2 is associated with the development and prognosis of various cancers, yet the role of KPNA2 in ovarian carcinoma and its potential molecular mechanisms remains unclear.

Materials and methods
The expression and prognosis of KPNA2 in ovarian cancer was investigated using GEPIA and Oncomine analyses. Mutations of KPNA2 in ovarian cancer were analyzed by cBioPortal database. The prognostic value of KPNA2 expression was evaluated by our own ovarian carcinoma samples using RT-qPCR. Subsequently, the cell growth, migration and invasion of ovarian cancer cells were investigated by CCK-8 and transwell assay, respectively. The protein levels of KPNA2 and KIF4A were determined by western blot.

Results
We obtained the following important results. (1) KPNA2 and KIF4A wereoverexpressed in ovairan cancer tissues and cells. (2) Among patients with ovarian cancer, overexpressed KPNA2 was associated with lower survival rate. (3) Mutations (R197* and S140F) in KPNA2 will have some influences on protein structure, and then may cause protein function abnormal. (4) KPNA2 konckdown inhibited proliferation, migration, invasion, as well as the expression of KIF4A.

Conclusion
KPNA2, as a tumorigenic gene in ovarian cancer, accelerated tumor progression by up-regulating KIF4A, suggesting that KPNA2 might be a hopeful indicator of treatment and poor prognosis.
Clinical outcomes and safety of passive leg raising in out-of-hospital cardiac arrest: a randomized controlled trial
Authors: Azeli Youcef , Bardají Alfredo , Barbería Eneko , Lopez-Madrid Vanesa , Bladé-Creixenti Jordi , Fernández-Sender Laura , Bonet Gil , Rica Elena , Álvarez Susana , Fernández Alberto , Axelsson Christer , Jiménez-Herrera Maria F. 
Published: May 2021

Abstract
Background
There are data suggesting that passive leg raising (PLR) improves hemodynamics during cardiopulmonary resuscitation (CPR). This trial aimed to determine the effectiveness and safety of PLR during CPR in out-of-hospital cardiac arrest (OHCA).

Methods
We conducted a randomized controlled trial with blinded assessment of the outcomes that assigned adults OHCA to be treated with PLR or in the flat position. The trial was conducted in the Camp de Tarragona region. The main end point was survival to hospital discharge with good neurological outcome defined as cerebral performance category (CPC 1–2). To study possible adverse effects, we assessed the presence of pulmonary complications on the first chest X-rays, brain edema on the computerized tomography (CT) in survivors and brain and lungs weights from autopsies in non-survivors.

Results
In total, 588 randomized cases were included, 301 were treated with PLR and 287 were controls. Overall, 67.8% were men and the median age was 72 (IQR 60–82) years. At hospital discharge, 3.3% in the PLR group and 3.5% in the control group were alive with CPC 1–2 (OR 0.9; 95% CI 0.4–2.3, p = 0.91). No significant differences in survival at hospital admission were found in all patients (OR 1.0; 95% CI 0.7–1.6, p = 0.95) and among patients with an initial shockable rhythm (OR 1.7; 95% CI 0.8–3.4, p = 0.15). There were no differences in pulmonary complication rates in chest X-rays [7 (25.9%) vs 5 (17.9%), p = 0.47] and brain edema on CT [5 (29.4%) vs 10 (32.6%), p = 0.84]. There were no differences in lung weight [1223 mg (IQR 909–1500) vs 1239 mg (IQR 900–1507), p = 0.82] or brain weight [1352 mg (IQR 1227–1457) vs 1380 mg (IQR 1255–1470), p = 0.43] among the 106 autopsies performed.

Conclusion
In this trial, PLR during CPR did not improve survival to hospital discharge with CPC 1–2. No evidence of adverse effects has been found.
Clinical trial registration
ClinicalTrials.gov: NCT01952197, registration date: September 27, 2013, https://clinicaltrials.gov/ct2/show/NCT01952197.
Genome-wide DNA mutations in Arabidopsis plants after multigenerational exposure to high temperatures
Authors: Lu Zhaogeng , Cui Jiawen , Wang Li , Teng Nianjun , Zhang Shoudong , Lam Hon-Ming , Zhu Yingfang , Xiao Siwei , Ke Wensi , Lin Jinxing , Xu Chenwu , Jin Biao 
Published: May 2021

Abstract
Background
Elevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological evolution. However, how long-term elevations in temperature influence the accumulation of mutations in plants remains unknown.

Results
Multigenerational exposure of Arabidopsis MA (mutation accumulation) lines and MA populations to extreme heat and moderate warming results in significantly increased mutation rates in single-nucleotide variants (SNVs) and small indels. We observe distinctive mutational spectra under extreme and moderately elevated temperatures, with significant increases in transition and transversion frequencies. Mutation occurs more frequently in intergenic regions, coding regions, and transposable elements in plants grown under elevated temperatures. At elevated temperatures, more mutations accumulate in genes associated with defense responses, DNA repair, and signaling. Notably, the distribution patterns of mutations among all progeny differ between MA populations and MA lines, suggesting that stronger selection effects occurred in populations. Methylation is observed more frequently at mutation sites, indicating its contribution to the mutation process at elevated temperatures. Mutations occurring within the same genome under elevated temperatures are significantly biased toward low gene density regions, special trinucleotides, tandem repeats, and adjacent simple repeats. Additionally, mutations found in all progeny overlap significantly with genetic variations reported in 1001 Genomes, suggesting non-uniform distribution of de novo mutations through the genome.

Conclusion
Collectively, our results suggest that elevated temperatures can accelerate the accumulation, and alter the molecular profiles, of DNA mutations in plants, thus providing significant insight into how environmental temperatures fuel plant evolution.
Demonstrating trustworthiness when collecting and sharing genomic data: public views across 22 countries
Authors: Milne Richard , Morley Katherine I. , Almarri Mohamed A. , Anwer Shamim , Atutornu Jerome , Baranova Elena E. , Bevan Paul , Cerezo Maria , Cong Yali , Costa Alessia , Critchley Christine , Fernow Josepine , Goodhand Peter , Hasan Qurratulain , Hibino Aiko , Houeland Gry , Howard Heidi C. , Hussain S. Zakir , Malmgren Charlotta Ingvoldstad , Izhevskaya Vera L. , Jędrzejak Aleksandra , Jinhong Cao , Kimura Megumi , Kleiderman Erika , Leach Brandi , Liu Keying , Mascalzoni Deborah , Mendes Álvaro , Minari Jusaku , Nicol Dianne , Niemiec Emilia , Patch Christine , Pollard Jack , Prainsack Barbara , Rivière Marie , Robarts Lauren , Roberts Jonathan , Romano Virginia , Sheerah Haytham A. , Smith James , Soulier Alexandra , Steed Claire , Stefànsdóttir Vigdis , Tandre Cornelia , Thorogood Adrian , Voigt Torsten H. , Wang Nan , West Anne V. , Yoshizawa Go , Middleton Anna 
Published: May 2021

Abstract
Background
Public trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.

Methods
We analyse the ‘Your DNA, Your Say’ online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.

Results
Providing transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data—endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.

Conclusions
Our findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
Hard wiring of normal tissue-specific chromosome-wide gene expression levels is an additional factor driving cancer type-specific aneuploidies
Authors: Patkar Sushant , Heselmeyer-Haddad Kerstin , Auslander Noam , Hirsch Daniela , Camps Jordi , Bronder Daniel , Brown Markus , Chen Wei-Dong , Lokanga Rachel , Wangsa Darawalee , Wangsa Danny , Hu Yue , Lischka Annette , Braun Rüdiger , Emons Georg , Ghadimi B. Michael , Gaedcke Jochen , Grade Marian , Montagna Cristina , Lazebnik Yuri , Difilippantonio Michael J. , Habermann Jens K. , Auer Gert , Ruppin Eytan , Ried Thomas 
Published: May 2021

Abstract
Background
Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood.

Methods
In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms.

Results
This analysis revealed a complex picture of factors driving tumor karyotype evolution in which some recurrent chromosomal copy number reflect the chromosome arm-wide gene expression levels of the their normal tissue of tumor origin.

Conclusions
We conclude that the cancer type-specific distribution of chromosomal arm gains and losses is potentially “hardwiring” gene expression levels characteristic of the normal tissue of tumor origin, in addition to broadly modulating the expression of tissue-specific tumor driver genes.
Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses
Authors: van Deuren Rosanne C. , Arts Peer , Cavalli Giulio , Jaeger Martin , Steehouwer Marloes , van de Vorst Maartje , Gilissen Christian , Joosten Leo A. B. , Dinarello Charles A. , Mhlanga Musa M. , Kumar Vinod , Netea Mihai G. , van de Veerdonk Frank L. , Hoischen Alexander 
Published: May 2021

AbstractBackgroundThe interleukin (IL)-1 pathway is primarily associated with innate immunological defense and plays a major role in the induction and regulation of inflammation. Both common and rare genetic variation in this pathway underlies various inflammation-mediated diseases, but the role of rare variants relative to common variants in immune response variability in healthy individuals remains unclear.MethodsWe performed molecular inversion probe sequencing on 48 IL-1 pathway-related genes in 463 healthy individuals from the Human Functional Genomics Project. We functionally grouped common and rare variants, over gene, subpathway, and inflammatory levels and performed the Sequence Kernel Association Test to test for association with in vitro stimulation-induced cytokine responses; specifically, IL-1β and IL-6 cytokine measurements upon stimulations that represent an array of microbial infections: lipopolysaccharide (LPS), phytohaemagglutinin (PHA),Candida albicans(C. albicans), andStaphylococcus aureus(S. aureus).ResultsWe identified a burden ofNCF4rare variants with PHA-induced IL-6 cytokine and showed that the respective carriers are in the 1% lowest IL-6 producers. Collapsing rare variants in IL-1 subpathway genes produces a bidirectional association with LPS-induced IL-1β cytokine levels, which is reflected by a significant Spearman correlation. On the inflammatory level, we identified a burden of rare variants in genes encoding for proteins with an anti-inflammatory function withS. aureus-induced IL-6 cytokine. In contrast to these rare variant findings which were based on different types of stimuli, common variant associations were exclusively identified withC. albicans-induced cytokine over various levels of grouping, from the gene, to subpathway, to inflammatory level.ConclusionsIn conclusion, this study shows that functionally grouping common and rare genetic variants enables the elucidation IL-1-mediated biological mechanisms, specifically, for IL-1β and IL-6 cytokine responses induced by various stimuli. The framework used in this study may allow for the analysis of rare and common genetic variants in a wider variety of (non-immune) complex phenotypes and therefore has the potential to contribute to better understanding of unresolved, complex traits and diseases.