bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidental Pulmonary Embolism. Analysis of Mayo Clinic Venous Thromboembolism Database
Authors: Wysokinska Ewa , Houghton Damon E. , Vlazny Danielle , Ashrani Aneel A. , Froehling David A , Hodge David O. , Peterson Lisa , McBane Robert D. , Wysokinski Waldemar E. , Casanegra Ana I 
Published: November 2019

Background: Incidental pulmonary embolism (PE) is not infrequently found on CT scans with highest incidence reported in patients with cancer. It is unclear whether patients with symptomatic pulmonary embolism (iPE) have different clinical profile or outcomes compared to patients with symptomatic PE (sPE) and whether this is affected by the presence or type of malignancy.
Objective: Compare baseline characteristics of patients diagnosed with iPE to patients with sPE with attention to cancer-specific risk factors as well as evaluate clinical outcomes.
Methods: Consecutive patients enrolled in the Mayo Thrombophilia Clinic VTE Registry between March 1, 2013 and December 31st, 2018 with PE were followed prospectively. Outcomes of recurrent venous thromboembolism (VTE), major bleeding, clinically relevant non-major bleeding (CRNMB) and mortality data were collected every 3 months. Clinical outcomes were analyzed with specific focus on patients with cancer. Information was collected and managed using REDCap (Research Electronic Data Capture) and data analysis was performed using SAS software (SAS Institute Inc., Cary, North Carolina).
Results: Out of a total of 1033 patients with PE in VTE registry, there were 655 patients with PE (284 with incidental and 363 symptomatic) who completed at least 3 months of anticoagulation and were started on treatment within 14 days of diagnosis. Apixaban was used in 220 (34 %), Rivaroxaban 175 (27 %), Enoxaparin 179 (27%), and Warfarin in 81 (12 %) patients.
Overall cancer was present in 61% of patients and was more common in patients with iPE compared to sPE (80.2% vs 45.2%, p<0.001).
Patients with iPE were less likely to have previous VTE (8.2% vs 25.5%, p< 0.0001) and tended to have lower BMI (mean 28.8 vs 31.4, p<0.0001)
Characteristics of the subgroup of only cancer patients with PE are summarized in the Table.
Of note, pancreatic and GI cancers were more common in patients with iPE.
There were no differences in recurrent VTE, major bleeding and CRNMB in patients with iPE compared to sPE. This also held true for patients with underlying malignancies. Mortality rates were significantly higher in all patients with iPE even when adjusting for presence of malignancy (p=0.03). When adjusting for presence of metastatic malignancy though the difference was no longer present (p=0.33).
Conclusion: Patients with iPE were more likely to have an underlying malignancy, potentially due to higher likelihood of undergoing staging imaging studies. Additionally, patients with iPE more often had metastatic disease which was associated with higher mortality. Recurrent VTE and bleeding outcomes were similar in patients with iPE and sPE, this was independent of the presence of underlying malignancy.

Disclosures
McBane: BMS: Research Funding.
Ferroportin Downregulation Promotes Cell Proliferation By Modulating the Nrf2-Mir 17-5p Axis in Multiple Myeloma
Authors: Shi Jumei , Kong Yuanyuan , Hu Liangning , Chen Gege , Yu Dandan , Xie Yongsheng , Wang Yingcong , Wu Xiaosong 
Published: November 2019

Recent findings demonstrate that aberrant downregulation of the iron-exporter protein, ferroportin (FPN1), is associated with poor prognosis and osteoclast differentiation in multiple myeloma (MM). Here, we show that FPN1 was downregulated in MM and that clustered regularly interspaced short palindromic repeat (CRISPR)-mediated FPN1 knockout promoted MM cell growth and survival. Using an microRNA target-scan algorithm, we identified miR 17-5p as an FPN1 regulator that promoted cell proliferation and cell cycle progression, and inhibited apoptosis - both in vitro and in vivo. miR 17-5p inhibited retarded tumor growth in a MM xenograft model. Moreover, restoring FPN1 expression at least partially abrogated the biological effects of miR 17-5p in MM cells. The cellular iron concentration regulated the expression of the iron-regulatory protein (IRP) via the 5-untranslated region of IRP messenger RNA and modulated the post-transcriptional stability of FPN1. Bioinformatics analysis with subsequent chromatin immunoprecipitation-polymerase chain reaction and luciferase activity experiments revealed that the transcription factor Nrf2 drove FPN1 transcription through promoter binding and suppressed miR 17-5p (which also increased FPN1 expression). Nrf2-mediated FPN1 downregulation promoted intracellular iron accumulation and reactive oxygen species. Our study links FPN1 transcriptional and post-transcriptional regulation with MM cell growth and survival, and validates the prognostic value of FPN1 and its utility as a novel therapeutic target in MM.
Figure 1

Disclosures
No relevant conflicts of interest to declare.
Impaired Bile Secretion Promotes Chronic Liver Injury in Sickle Cell Disease
Authors: Pradhan Tirthadipa , Sundd Prithu , Gladwin Mark T , Monga Satdarshan Pal , Kato Gregory J 
Published: November 2019

Hepatic crisis is an emergent complication affecting sickle cell disease (SCD) patients, however, the molecular mechanism of sickle cell hepatobiliary crisis remains poorly understood. We examined the liver pathophysiology of SCD using a humanized mouse model (townes SCD mice; homozygous for Hbatm1(HBA)Tow, homozygous for Hbbtm2(HBG1,HBB*)Tow). These mice have the major features (irreversibly sickled red cells, splenomegaly, anemia, multiorgan pathology) found in humans with SCD and, as such, represent a useful in vivo system to study hepatobiliary changes in SCD disease.
SCD mice manifested progressive hepatomegaly, liver injury and hyperbilirubinemia. RNA-sequence analysis of total RNA from SCD mouse liver compared to control (AS) identified dysregulation of genes encoding proteins responsible for fibrosis, bile acid synthesis, bile transport and cholesterol metabolism. Immunohistochemical analysis confirmed inflammation, fibrosis and increased ductular reaction in SCD mice. To mechanistically address the cholestatic phenotype in SCD mice, we used our recently developed multi-photon-excitation (MPE) enabled in vivo real-time fluorescence microscopy of intact liver in live mice. We used Texas-Red (TXR) dextran to visualize the blood flow through liver sinusoids and carboxyfluorescein (used as a surrogate of bile flow) to visualize bile flow through biliary canaliculi. Real time imaging show that sinusoidal ischemia occurs in the liver of transgenic-humanized SCD mice under basal condition. Intravital imaging also revealed impaired bile secretion into the bile canaliculi, which was associated with loss of apical bile acid transporters and bile acid biosynthetic enzymes, hepatic bile accumulation, and activation of Farnesoid X receptor (FXR) and small heterodimer partner (Shp) in the liver of SCD mice. These findings are the first to identify that impaired bile acid synthesis and misexpression of bile transporters promote intrahepatic bile accumulation and impaired bile secretion, leading to hepatobiliary injury of SCD. Improved understanding of these processes could potentially benefit the development of new therapies to treat sickle cell hepatic crisis.

Disclosures
Gladwin: Globin Solutions, Inc: Patents & Royalties: Provisional patents for the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning; Bayer Pharmaceuticals: Other: Co-investigator; United Therapeutics: Patents & Royalties: Co-inventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases . Kato:Novartis, Global Blood Therapeutics: Consultancy, Research Funding; Bayer: Research Funding.
Impact of Asthma on Inpatient Outcome of Sickle Cell Crisis: A Population-Based Study
Authors: Gong Zimu , Ali Faisal Shaukat S , Zhao Yu , Garcia Jessica Lee 
Published: November 2019

Introduction: Sickle cell disease (SCD) is one of the most common inherited hematological disorder in the United States. Sickle cell crisis is a common complication caused by excessive sickling of red blood cells, resulting in tissue ischemia. The frequency of such pain crisis, however, varies greatly among patients depending on disease control and other patient characteristics. Asthma is a common comorbidity in SCD patients which is associated with higher incidence of acute chest syndrome (ACS). However, the impact of asthma on short term outcome of acute sickle cell crisis remains unclear.
Methods: We analyzed data from the National Inpatient Sample database. Data entries from year 2005 through 2014 were included. The presence of SCD, sickle cell crisis, ACS, asthma are identified using corresponding ICD codes. Data regarding demographic information, performed procedures, inpatient mortality, and length of stay are extracted and analyzed accordingly.
Results: A total of 247,266 records were identified. The median age at admission was 26 years (interquartile range 18 - 37), with most patients being of African American origin (91.8%). A total of 16,828 (6.8%) patients presented with ACS, whereas 173,869 (70.3%) presented with non-ACS crisis. The remaining 56,569 (22.9%) patients were admitted for reasons other than sickle cell crisis, most commonly infection. Overall, 34,609 patients (14.0%) had asthma. Compared to patients without ACS, the incidence of asthma was significantly higher in patients with ACS (19.0% vs 13.6%, P<0.001), whereas patients with non-ACS crisis had a similar incidence of asthma compared to those without sickle cell crisis (13.7% vs 13.5%, P=0.42). Asthma patients who presented with ACS exhibited a lower inpatient mortality (0.4% vs 1.1%, P<0.001), as well as lower use of invasive mechanical ventilation (3.0% vs 4.1%, P=0.006). Similarly, in patients with non-ACS sickle cell crisis, asthma was associated with lower mortality (0.4% vs 0.2%, P<0.001), lower use of invasive mechanical ventilation (0.4% vs 0.7%, P<0.001), and lower frequency of transfusion (27.5% vs 31.9%, P<0.001).
Conclusion: Our study again demonstrated the association between asthma and ACS in SCD patients. Furthermore, asthma appears to be associated with superior outcome in both patients with ACS and non-ACS sickle cell crisis. Further studies are warranted to elucidate if asthma is associated with a milder form of sickle cell crisis which may correlate with the physiologic basis of these associations.

Disclosures
No relevant conflicts of interest to declare.
Does knowledge of evolutionary biology change high school students’ attitudes about healthy eating?
Authors: Sherry Diana S. 
Published: November 2019

AbstractBackgroundEmbedded in the emerging area of evolutionary medicine is the premise that evolutionary biology can serve a pedagogical function with widespread applications for education and outreach. Although great strides have been taken over the decades by the science education community to improve evolution education in general, the knowledge gulf or gap between advances in evolutionary medicine and public understanding through the educational system has widened at a rapid pace—and not without consequences for public health, especially for young people. Epidemiological data indicate that the high rates of obesity and type-2 diabetes have begun to extend to adolescents and teenagers, an alarming trend of great concern. Would knowledge of the evolutionary biology perspective on diet and health have value for young people? Little is known about the efficacy of evolutionary medicine education as a public health outreach strategy. A small study was conducted at a New England high school and consisted of two research components: (1) a cross-sectional survey of students’ views about what “healthy eating” means and (2) an intervention experiment designed to isolate exposure to knowledge of evolutionary biology. Data were collected through the use of questionnaires and analyzed according to qualitative methods.ResultsThe survey results showed that students had an accurate view of general guidelines for healthy eating in alignment with public health messaging (e.g., avoiding junk food, eating lots of fruits and vegetables). The main result from the intervention experiment showed that students who received instruction in nutritional physiology alone did not change their view of what “healthy eating” means, whereas students who received instruction in nutritional physiology coupled with evolutionary biology changed their views of healthy food choices, leading to intended dietary changes.ConclusionsA brief, one-time exposure to key concepts in evolutionary biology brought about a shift in students’ perceptions of healthy eating. An approach that can cause a shift in perception or attitude, considered an essential first step toward effecting behavioral change, merits further attention and development. Evolutionary medicine education holds strong potential as an untapped yet effective public health outreach strategy regarding the dietary choices of youth.
A compulsive act of excess water intake leading to hyponatraemia and rhabdomyolysis: a case report
Authors: Fernando Sudheera , Sivagnanam Francisca , Rathish Devarajan 
Published: November 2019

Abstract
Background
Primary polydipsia is commonly seen in patients with psychiatric illnesses. Excess water intake is also seen in patient with anorexia and anticholinergic medications. We report a patient who had hyponatraemia and rhabdomyolysis after consuming excess water for ureteric calculus.

Case presentation
A healthy middle-aged male presented with an episode of generalized tonic-clonic seizure and reduced level of consciousness preceded by consumption of excess water. He was recently diagnosed to have a ureteric calculus and was advised to consume plenty of water. On examination, he was disoriented in place, person and time. Except for the generalized diminished reflexes, other neurological and systemic examinations were normal. He had severe hyponatraemia, mild hypokalaemia and myoglobulinuria. His serum creatinine phosphokinase and aspartate aminotransferase were markedly elevated. The diagnosis of rhabdomyolysis in the setting of acute water intoxication was made. Optimum fluid and electrolyte management achieved a dramatic recovery of consciousness, hyponatraemia and rhabdomyolysis.

Discussion
The patient has had excess water intake due to a compulsive act in the background fear of ureteric calculus. Such act could lead to severe hyponatraemia and rhabdomyolysis. Therefore, future similar acts could be prevented by proper medical advice. Further, emergency physicians should be vigilant for rhabdomyolysis in patients with hyponatraemia or hypokalaemia.
Involvement of OsGF14b Adaptation in the Drought Resistance of Rice Plants
Authors: Liu Jianping , Sun Xinjiao , Liao Wencheng , Zhang Jianhua , Liang Jiansheng , Xu Weifeng 
Published: November 2019

Abstract
Background
Drought stress is one of the major abiotic stresses that restrict plant growth and development. 14–3-3 proteins have been validated to regulate many biological processes in plants. Previous research demonstrated that OsGF14b plays different roles in panicle and leaf blast resistance. In this study, we researched the function of OsGF14b in drought resistance in rice.

Findings
Here, we report that OsGF14b was strongly induced by soil drought stress. In comparison with wild type (WT), the osgf14b mutant exhibited improved resistance to drought and osmotic stress by changing the content of stress-relevant parameters, complementation of the osgf14b mutant restored the drought sensitivity to WT levels, whereas the OsGF14b-overexpression lines exhibited enhanced sensitivity to drought and osmotic stress. The osgf14b mutant plants were hypersensitive to abscisic acid (ABA), while the OsGF14b-overexpression plants showed reduced sensitivity to ABA. Furthermore, mutation and overexpression of OsGF14b affected the expression of stress-related genes under normal growth conditions and/or drought stress conditions.

Conclusions
We have demonstrated that OsGF14b is involved in the drought resistance of rice plants, partially in an ABA-dependent manner.
LOVE ON WINGS, a Dof family protein regulates floral vasculature in Vigna radiata
Authors: Guo Wuxiu , Zhang Xue , Peng Qincheng , Luo Da , Jiao Keyuan , Su Shihao 
Published: November 2019

Abstract
Background
The interaction among plants and their pollinators has been a major factor which enriched floral traits known as pollination syndromes and promoted the diversification of flowering plants. One of the bee-pollination syndromes in Faboideae with keel blossoms is the formation of a landing platform by wing and keel petals. However, the molecular mechanisms of elaborating a keel blossom remain unclear.

Results
By performing large scale mutagenesis, we isolated and characterized a mutant in Vigna radiata, love on wings (low), which shows developmental defects in petal asymmetry and vasculature, leading to a failure in landing platform formation. We cloned the locus through map-based cloning together with RNA-sequencing (RNA-seq) analysis. We found that LOW encoded a nucleus-localized Dof-like protein and was expressed in the flower provascular and vascular tissues. A single copy of LOW was detected in legumes, in contrast with other taxa where there seems to be at least 2 copies. Thirty one Dof proteins have been identified from the V. radiata’s genome, which can be further divided into four Major Cluster of Orthologous Groups (MCOGs). We also showed that ectopic expression of LOW in Arabidopsis driven by its native promoter caused changes in petal vasculature pattern.

Conclusions
To summarize, our study isolated a legume Dof-like factor LOW from V. radiata, which affects vasculature development in this species and this change can, in turn, impact petal development and overall morphology of keel blossom.
Interpreter proxy versus healthcare interpreter for administration of patient surveys following arthroplasty: a pilot study
Authors: Xue Daniel , Churches Timothy , Armstrong Elizabeth , Mittal Rajat , Naylor Justine Maree , Harris Ian Andrew 
Published: November 2019

Abstract
Background
Clinical quality registries and other systems that conduct routine post-discharge surveillance of patient outcomes following surgery may have difficulty surveying patients who have limited proficiency in the language of the healthcare provider. Interpreter proxies (family and carers) are often used due to limited access to certified healthcare interpreters (due to cost or availability). The aim of this study was to assess the reliability of engaging interpreter proxies compared with certified healthcare interpreters for the administration of patient-reported health-related surveys for people with limited English proficiency (LEP).

Methods
People with LEP and due for a routine 6-month telephone follow-up post knee or hip arthroplasty were invited to participate. Participants were randomly allocated to having their first interview with an interpreter proxy or a certified healthcare interpreter followed by the second (crossover) interview within 2 weeks (range: 4 to 12 days) after the first interview using the alternative method. Agreement between the two methods was assessed using quadratic weighted Cohen’s kappa, intraclass correlation and concordance correlation co-efficient where appropriate for EQ-5D health domains, total Oxford hip and knee scores, patient satisfaction, operation success, readmission, reoperation, and post-surgical complication responses. The mean of the differences between the same data items collected by each of the two methods was also calculated.

Results
Eighty five participants (96%) completed the study. There was substantial to excellent inter-rater agreement (kappa = 0.69–0.87 and ICCs above 0.74) for all but one measure. The mean differences between family proxy and healthcare interpreter scores for each participant were small, ranging from 0.01 (score range of 1–5) to 0.72 (score range of 0–100).

Conclusion
These results suggest that using interpreter proxies is a reliable alternative to certified healthcare interpreters in conducting patient-reported health surveys, potentially making this process easier and cost effective for researchers and registries.
Compound heterozygous LPIN2 pathogenic variants in a patient with Majeed syndrome with recurrent fever and severe neutropenia: case report
Authors: Liu Jun , Hu Xu-Yun , Zhao Zhi-Peng , Guo Ruo-Lan , Guo Jun , Li Wei , Hao Chan-Juan , Xu Bao-Ping 
Published: November 2019

Abstract
Background
Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA), and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for Majeed syndrome.

Case presentation
We report an 8-month-old boy, who presented with recurrent fever, mild to moderate anemia, and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular testing identified a paternal splicing donor site variant c.2327 + 1G > C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3) in LPIN2.

Conclusions
Only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, different from previous reports.