bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Myeloma, the Prognostic Impact of Hyperdiploidy Is Mainly Related to the Gain of Chromosome 5
Authors: Loiseau Herve Avet , Li Cheng , Magrangeas Florence , Guerin Catherine , Gouraud Wilfried , Harousseau Jean-Luc , Attal Michel , Marit Gerald , Mathiot Claire , Facon Thierry , Moreau Philippe , Anderson Kenneth C , Campion Loic , Munshi Nikhil C. , Minvielle Stephane 
Published: April 2020

Abstract
Multiple myeloma is characterized by multiple chromosomal abnormalities, and virtually 100% of the patients are cytogenetically abnormal. Among the few recurrent changes described, hyperdiploidy is one of the most frequent. In cytogenetic series, hyperdiploidy is reported in 50 to 60% of the cases. It has been associated with prolonged survival in some series, whereas other series concluded to a neutral prognostic impact. These conflicting data might be related to the bias of cytogenetic analyses, which are abnormal in only 10 to 30% of the cases. In order to circumvent the pitfall of the low proliferation of plasma cells, we conducted a study based on DNA microarray. A series of 192 patients presenting multiple myeloma at diagnosis and treated homogeneously in tandem transplantation IFM trials were analyzed using the 500K Affymetrix SNP-arrays. In agreement with cytogenetic series, hyperdiploidy (&gt; 47 chromosomes) was observed in 99 patients (53%). As previously reported, the most frequently gained chromosomes were chromosomes 3, 5, 7, 9, 11, 15, 19, 21, and X in female patients. We did perform a prognostic analysis. Hyperdiploid patients displayed a clear survival advantage as compared with non-hyperdiploid patients: p=0.006 and p=0.0008 for event free survival (EFS) and overall survival (OS), respectively. When adding all the chromosomal abnormalities observed on the SNP-arrays, 3 chromosomal lesions were independently associated with prognosis : gain of 1q, loss of 12p, and gain of chromosome 5. If serum b2- microglobulin (sb2m) level and t(4;14) were entered in the model, only sb2m, del(12p) and gain of chromosome 5, kept an independent prognostic value. These data suggest that most of the prognostic impact of hyperdiploidy could be linked to the gain of chromosome 5 (p=0.0001 and p&lt;0.0001, for EFS and OS, respectively). In order to test this hypothesis, we did compare the survival of hyperdiploid patients with gain of chromosome 5 to that of hyperdiploid patients lacking chromosome 5 gain. As expected, patients with chromosome 5 gain displayed a significantly longer EFS and OS than those lacking this gain (p=0.005 and p=0.001 for EFS and OS, respectively). In conclusion, this study suggests that most of the prognostic value of hyperdiploidy is actually borne by chromosome 5.
Prospective Validation of the Peds Clot Clinical Decision Rule [Pdcr] in Hospital-Acquired Venous Thromboembolism: An Interim Analysis
Authors: Schultz Rachael F , Kwon Soyang , Sharathkumar Anjali , Bhat Rukhmi 
Published: April 2020

Abstract
Background: Venous thromboembolism (VTE) is an emerging hospital acquired complication in pediatric hospitals. Substantial efforts have been made to identify high-risk population based on exposure to risk-factors for VTE. Our group developed the PedsClot Clinical Decision Rule (Sharathkumar et al Journal of Thrombosis and Haemostasis, 10: 1326-1334) to identify this high-risk population based on a case-control study but this has not been validated yet.
Objective: To validate thePedsClot Clinical Decision Rule [PDCR] through prospective collection of data in a tertiary pediatric hospital. This study reports our findings of interim analyses for process evaluation.
Methods: This prospective data collection was performed using the Lurie Children's hospital automatic data import facility through the Enterprise Data Warehouse[study period: 02/01/2012-12/31/14]. Real time data was added to a research database of consecutive admissions based on following inclusion criteria: &gt; 48 hour stay in the Intensive Care (Pediatric, Cardiac, Neonatal), Hematology Oncology and Infectious Disease units. Following variables were included in the dataset: age, sex, ethnicity, date of admission and discharge, ICU admission, central venous catheter (CVC), blood stream infection, immobilization, oral contraceptives, mechanical ventilation&gt; 12hrs, and length of stay. Risk factors were weighed and scored as per PDCR rule. Chi-square tests were used to examine the association between the potential risk factors and VTE. PDCR model performance was evaluated by reporting the sensitivity and specificity.
Results: A total of 1722 children were eligible for the interim analyses. The demographic and clinical features of the dataset analyses and the odds ratio [OR] are detailed in Table 1 and 2 respectively. Of 1722 patients, 57 (3.3%) were identified as VTE, 50% were admitted to the ICU and 51% had a CVC. VTE was associated with age ≥ 13 years (AOR=2.3; 95% CI=1.3, 4.0), ICU admission (AOR=2.4; 95% CI=1.3, 4.4), and CVC (AOR=1.9; 95% CI=1.1, 3.3). The model performance showed that at the cut off point of 3, the specificity of the PDCR in predicting VTE was 75% but had a low sensitivity (37%). Risk prediction variables such as assessment of immobilization, use of oral contraceptives and prediction of hospital stay required manual entry into the datasheet; this makes data-capture labor intensive, especially for larger datasets.
Conclusions: This study utilized technological advances and database warehouse facility to validate PDCR. This interim data analyses indicates that in real life, PDCR has a high specificity but poor sensitivity in identifying children with predisposition for VTE. We are currently working to refine the risk model which may lead to a better model performance.

Disclosures
Sharathkumar: Bayer, Baxter, CSL Behring: Consultancy.
A Single Genetic Origin for a Common Caucasian Risk Factor for Venous Thrombosis
Authors: Zivelin Ariella , Griffin John H. , Xu Xiao , Pabinger Ingrid , Samama Michel , Conard Jacqueline , Brenner Benjamin , Eldor Amiram , Seligsohn Uri 
Published: April 2020

AbstractA common genetic risk factor for venous thrombosis among Caucasoid subpopulations is a polymorphism, nt G1691A, in blood coagulation factor V that replaces Arg506 with Gln and imparts resistance of factor Va to the anticoagulant, activated protein C. Haplotype analyses using six dimorphic sites in the factor V gene for 117 Caucasian subjects of Jewish, Arab, Austrian, and French origin who were homozygous for nt A1691 compared with 167 controls (nt G1691) support a single origin for this polymorphism. The nt G1691A mutation is estimated to have arisen circa 21,000 to 34,000 years ago, ie, after the evolutionary divergence of Africans from non-Africans and of Caucasoid from Mongoloid subpopulations.
A microsimulation model to assess the economic impact of immunotherapy in non-small cell lung cancer
Authors: Legoupil Clémence , Debieuvre Didier , Marabelle Aurelien , Michiels Stefan , Kapso Raïssa , Besse Benjamin , Bonastre Julia 
Published: April 2020

IntroductionImmunotherapy has become the standard of care in advanced non-small cell lung cancer (NSCLC). We aimed to quantify the economic impact, in France, of anti-PD-1 therapy for NSCLC.MethodsWe used patient-level data from the national ESCAP-2011-CPHG cohort study to estimate time to treatment failure and mean cost per patient for the four label indications approved by the European Medicines Agency (EMA) for NSCLC in May 2018. To compute the budget impact, we used a microsimulation model to estimate the target populations of anti-PD-1 therapy over a 3-year period, which were combined with the annual cost of treatment.ResultsOverall, 11 839 patients with NSCLC were estimated to be eligible for anti-PD-1 therapy 3 years after the introduction of anti-PD-1 therapies. The mean annual cost per patient in the control group ranged from €2671 (95% CI €2149–3194) to €6412 (95% CI €5920–6903) across the four indications. The mean annual cost of treatment for the four EMA-approved indications of anti-PD-1 therapy was estimated to be €48.7 million in the control group and at €421.8 million in the immunotherapy group. The overall budget impact in 2019 is expected to amount to €373.1 million. In the sensitivity analysis, flat doses and treatment effect had the greatest influence on the budget impact.ConclusionAnti-PD-1 agents for NSCLC treatment are associated with a substantial economic burden.
Prevalence and incidence of, and risk factors for chronic cough in the adult population: the Rotterdam Study
Authors: Arinze Johnmary T. , de Roos Emmely W. , Karimi Leila , Verhamme Katia M.C. , Stricker Bruno H. , Brusselle Guy G. 
Published: April 2020

Chronic cough is a common complaint in the general population but there are no precise data on the incidence of, and prospectively examined risk factors for chronic cough in a population-based setting. Therefore, we investigated the period prevalence, incidence and risk factors for chronic cough in adult subjects.In a prospective population-based cohort study among subjects aged ≥45 years, data on chronic cough were collected on two separate occasions using a standardised questionnaire. Chronic cough was defined as daily coughing for at least 3 months duration during the preceding 2 years. Potential risk factors were gathered by interview, physical examination and several investigations.Of the 9824 participants in this study, 1073 (10.9%) subjects had chronic cough at baseline. The prevalence of chronic cough increased with age and peaked in the eighth decade. In subjects aged <70 years, chronic cough was more common in women. During an average follow-up of 6 years, 439 incident cases of chronic cough occurred with an overall incidence rate of 11.6 per 1000 person-years (95% CI 10.6–12.8). In current smokers, the incidence of chronic cough was higher in men. In the multivariable analysis, current smoking, gastro-oesophageal reflux disease (GORD), asthma and COPD were identified as risk factors for chronic cough.Chronic cough is common among adults and highly prevalent in the older population. Current smoking, GORD, asthma and COPD are independent risk factors for chronic cough. Individuals at risk of developing chronic cough may benefit from smoking cessation and control of the underlying disease.
Short paired-end reads trump long single-end reads for expression analysis
Authors: Freedman Adam H. , Gaspar John M. , Sackton Timothy B. 
Published: April 2020

Abstract
Background
Typical experimental design advice for expression analyses using RNA-seq generally assumes that single-end reads provide robust gene-level expression estimates in a cost-effective manner, and that the additional benefits obtained from paired-end sequencing are not worth the additional cost. However, in many cases (e.g., with Illumina NextSeq and NovaSeq instruments), shorter paired-end reads and longer single-end reads can be generated for the same cost, and it is not obvious which strategy should be preferred. Using publicly available data, we test whether short-paired end reads can achieve more robust expression estimates and differential expression results than single-end reads of approximately the same total number of sequenced bases.

Results
At both the transcript and gene levels, 2 × 40 paired-end reads unequivocally provide expression estimates that are more highly correlated with 2 × 125 than 1 × 75 reads; in nearly all cases, those correlations are also greater than for 1 × 125, despite the greater total number of sequenced bases for the latter. Across an array of metrics, differential expression tests based upon 2 × 40 consistently outperform those using 1 × 75.

Conclusion
Researchers seeking a cost-effective approach for gene-level expression analysis should prefer short paired-end reads over a longer single-end strategy. Short paired-end reads will also give reasonably robust expression estimates and differential expression results at the isoform level.
Nuclear phylogeography of the temperate tree species Chiranthodendron pentadactylon (Malvaceae): Quaternary relicts in Mesoamerican cloud forests
Authors: Hernández-Langford Diana Gabriela , Siqueiros-Delgado María Elena , Ruíz-Sánchez Eduardo 
Published: April 2020

AbstractBackgroundTheMexican hand treeorCanac(Chiranthodendron pentadactylon) is a temperate tree species of cloud and pine-oak forests of southern Mexico and Guatemala. Its characteristic hand-shaped flower is used in folk medicine and has constituted the iconic symbol of theSociedad Botánica de Méxicosince 1940. Here, the evolutionary history of this species was estimated through phylogeographic analyses of nuclear DNA sequences obtained through restriction site associated DNA sequencing and ecological niche modeling. Total genomic DNA was extracted from leaf samples obtained from a representative number (5 to 10 per sampling site) of individuals distributed along the species geographic range. In Mexico, population is comprised by spatially isolated individuals which may follow the trends of cloud forest fragmentation. By contrast, in GuatemalaChiranthodendronmay constitute a canopy dominant species near the Acatenango volcano. The distributional range of this species encompasses geographic provinces separated by the Isthmus of Tehuantepec.The objectives of the study were to: (i) estimate its genetic structure to define whether the observed range disjunction exerted by the Isthmus of Tehuantepec translates into separate populations, (ii) link population divergence timing and demographic trends to historical climate change, and (iii) test hypotheses related to Pleistocene refugia.ResultsPatterns of genetic diversity indicated high levels of genetic differentiation between populations separated by the Isthmus. The western and eastern population diverged approximately 0.873 Million years ago (Ma). Demographic analyses supported a simultaneous split from an ancestral population and rapid expansion from a small stock approximately 0.2 Ma corresponding to a glacial period. The populations have remained stable since the LIG (130 Kilo years ago (Ka)). Species distribution modelling (SDM) predicted a decrease in potential distribution in the Last Interglacial (LIG) and an increase during the Last Glacial Maximum (LGM) (22 Ka), Mid-Holocene (6 Ka) and present times.ConclusionsDivergence time estimations support the hypothesis that populations represent Quaternary relict elements of a species with broader and northernmost distribution. Pleistocene climatic shifts exerted major influence on the distribution of populations allowing dispersion during episodes of suitable climatic conditions and structuring during the first interglacial with a time period length of 100 Kilo years (Kyr) and the vicariant influence of the Isthmus. Limited demographic expansion and population connectivity during the LGM supports the moist forest hypothesis model.
Protein changes as robust signatures of fish chronic stress: a proteomics approach to fish welfare research
Authors: Raposo de Magalhães Cláudia , Schrama Denise , Farinha Ana Paula , Revets Dominique , Kuehn Annette , Planchon Sébastien , Rodrigues Pedro Miguel , Cerqueira Marco 
Published: April 2020

AbstractBackgroundAquaculture is a fast-growing industry and therefore welfare and environmental impact have become of utmost importance. Preventing stress associated to common aquaculture practices and optimizing the fish stress response by quantification of the stress level, are important steps towards the improvement of welfare standards. Stress is characterized by a cascade of physiological responses that, in-turn, induce further changes at the whole-animal level. These can either increase fitness or impair welfare. Nevertheless, monitorization of this dynamic process has, up until now, relied on indicators that are only a snapshot of the stress level experienced. Promising technological tools, such as proteomics, allow an unbiased approach for the discovery of potential biomarkers for stress monitoring. Within this scope, using Gilthead seabream (Sparus aurata) as a model, three chronic stress conditions, namely overcrowding, handling and hypoxia, were employed to evaluate the potential of the fish protein-based adaptations as reliable signatures of chronic stress, in contrast with the commonly used hormonal and metabolic indicators.ResultsA broad spectrum of biological variation regarding cortisol and glucose levels was observed, the values of which rose higher in net-handled fish. In this sense, a potential pattern of stressor-specificity was clear, as the level of response varied markedly between a persistent (crowding) and a repetitive stressor (handling). Gel-based proteomics analysis of the plasma proteome also revealed that net-handled fish had the highest number of differential proteins, compared to the other trials. Mass spectrometric analysis, followed by gene ontology enrichment and protein-protein interaction analyses, characterized those as humoral components of the innate immune system and key elements of the response to stimulus.ConclusionsOverall, this study represents the first screening of more reliable signatures of physiological adaptation to chronic stress in fish, allowing the future development of novel biomarker models to monitor fish welfare.
Arabidopsis Chloroplast protein for Growth and Fertility1 (CGF1) and CGF2 are essential for chloroplast development and female gametogenesis
Authors: Zhu Rui-Min , Chai Sen , Zhang Zhuang-Zhuang , Ma Chang-Le , Zhang Yan , Li Sha 
Published: April 2020

Abstract
Background
Chloroplasts are essential organelles of plant cells for not only being the energy factory but also making plant cells adaptable to different environmental stimuli. The nuclear genome encodes most of the chloroplast proteins, among which a large percentage of membrane proteins have yet to be functionally characterized.

Results
We report here functional characterization of two nuclear-encoded chloroplast proteins, Chloroplast protein for Growth and Fertility (CGF1) and CGF2. CGF1 and CGF2 are expressed in diverse tissues and developmental stages. Proteins they encode are associated with chloroplasts through a N-terminal chloroplast-targeting signal in green tissues but also located at plastids in roots and seeds. Mutants of CGF1 and CGF2 generated by CRISPR/Cas9 exhibited vegetative defects, including reduced leaf size, dwarfism, and abnormal cell death. CGF1 and CGF2 redundantly mediate female gametogenesis, likely by securing local energy supply. Indeed, mutations of both genes impaired chloroplast integrity whereas exogenous sucrose rescued the growth defects of the CGF double mutant.

Conclusion
This study reports that two nuclear-encoded chloroplast proteins, Chloroplast protein for Growth and Fertility (CGF1) and CGF2, play important roles in vegetative growth, in female gametogenesis, and in embryogenesis likely by mediating chloroplast integrity and development.
Epicardial adipose tissue thickness as a potential predictor of gestational diabetes mellitus: a prospective cohort study
Authors: Liu Jing , Song Guang , Meng Tao , Zhao Ge 
Published: April 2020

Abstract
Background
Gestational diabetes mellitus (GDM) is the most common metabolic disorder that can occur during pregnancy and is associated with a long-term risk of both maternal and neonatal comorbidities. This study aimed to investigate the association between echocardiographic epicardial adipose tissue (EAT) and the risk for GDM during the early second trimester of pregnancy.

Method
We recruited all singleton pregnancies between January 2014 and December 2018 at 16 weeks + 0 days to 19 weeks + 6 days. We then used generalized linear models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for EAT as a potential predictor for GDM. Receiver-operating-characteristic (ROC) analysis was then conducted to investigate the discriminative capacity of any individual maternal factor for the prediction of GDM.

Results
In total, our study involved 314 pregnant women with GDM and 1832 pregnant women without GDM. Multivariate regression analysis revealed that EAT thickness (OR = 2.87; 95% CI: 2.49–3.31) was significantly associated with the presence of GDM (P < 0.001). Furthermore, EAT thickness was also significantly associated with a range of adverse outcomes in the GDM group, including large size for gestational age, neonatal hypoglycemia, admission to the neonatal intensive care unit, preterm delivery, and hyperbilirubinemia (P < 0.001). ROC analysis revealed that the area under the curve was 0.790 (95% CI: 0.768–0.812). When the cutoff value for EAT thickness was set to 5.49 mm, the sensitivity was 95.2% and the specificity was 50.5%.

Conclusions
Echocardiographic EAT thickness is positively and significantly associated with both the risk of GDM and adverse outcomes related to GDM. Echocardiographic EAT has the potential to predict GDM prior to actual clinical diagnosis.
Identifying and understanding the health and social care needs of Indigenous older adults with multiple chronic conditions and their caregivers: a scoping review
Authors: Webkamigad Sharlene , Rowe Robyn , Peltier Shanna , Froehlich Chow Amanda , McGilton Katherine S. , Walker Jennifer D. 
Published: April 2020

Abstract
Background
Indigenous people continue to experience high rates of multiple chronic conditions (MCC) at younger ages than other populations, resulting in an increase in health and social care needs. Those who provide services designed to address MCC for Indigenous communities require synthesized information to develop interventions that meet the needs of their older adult population. This review seeks to answer the research question: What are the health and social care needs, priorities and preferences of Indigenous older adults (living outside of long-term care settings) with MCC and their caregivers?

Methods
A scoping review, guided by a refinement of the Arksey & O’Malley framework, was conducted. Articles were included if the authors reported on health and social care needs and priorities of older Indigenous adults. We also included articles that focused on Indigenous conceptions of wellness, resilience, well-being, and/or balance within the context of aging, and articles where authors drew from Indigenous specific worldviews, ways of knowing, cultural safety, cultural competence, cultural appropriateness, cultural relevance and community needs.

Results
This scoping review included 9 articles that were examined using an Indigenous determinants of health (IDH) theoretical framework to analyze the needs of older adults and CGs. Five areas of needs were identified: accessible health services; building community capacity; improved social support networks; preservation of cultural values in health care; and wellness-based approaches.

Conclusion
The review highlights key determinants of health that influenced older adults’ needs: education and literacy, ethnicity, and social support/network (proximal); health promotion and health care (intermediate); and a combination of historical and contemporary structures (distal). The findings highlight the importance of local Indigenous knowledge and perspectives to improve accessibility of culturally relevant health and social services.