tbuckley/cabot-search huggingface dataset:
Variations in the Prevalence of Gestational Diabetes Mellitus With Remote Testing and a Pragmatic Solution to Improve Accuracy
Authors: Emma L. Jamieson, Erica P. Spry, Andrew B. Kirke, Carly Roxburgh, David N. Atkinson, Julia V. Marley
Journal: Diabetes Care (2020)

A recent article (1) and Commentary (2) in Diabetes Care have raised issues with respect to the method of handling blood samples for oral glucose tolerance tests (OGTT) and the prevalence of gestational diabetes mellitus (GDM). Many Australian sites continue to rely solely on collection tubes containing fluoride for stabilization of glucose. In outback Australia, this is a very real issue.

We previously estimated a two- to threefold increase in GDM prevalence in rural and remote Australia had the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study preanalytical protocol been used (from 10.8 to 28.5% [95% CI 20.8–29.5%]) (3). The impact of glycolysis is likely exacerbated in remote compared with urban settings due to greater distances to the laboratory—up to 650 km (400 miles) in our study (3).

Centrifugation within 10 min of sample collection can achieve glucose profiles similar to those with the HAPO study preanalytical protocol (3). Potter et al. (1) found a 1.8-fold increase in GDM prevalence after pathology laboratory collection centers implemented immediate centrifugation in a predominantly urban Australian setting. However, many rural and remote sites in …
Abstract 14306: Mural Cell SDF1 Signaling is Associated With the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Ke Yuan
Journal: Circulation (2020)

Introduction: Pericytes and pulmonary artery smooth muscle cells (PASMCs) are NG2+ mural cells that provide structural support to pulmonary vessels. In pulmonary arterial hypertension (PAH), both mural cell types contribute to PA muscularization, but whether distinct mechanisms that are responsible for their behavior is unclear. Methods: RNA-Seq was used to compare the gene profile of pericytes and PASMCs isolated from PAH and healthy lungs. NG2-CreER mice were used to generate tamoxifen-inducible NG2-selective reporter mice (NG2tdT fl/+ ) for cell lineage identification and for NG2-selective SDF1 knockout (SDF1 NG2-KO ). Results: Hierarchical clustering of RNA-seq data demonstrated that the genetic profile of PAH pericytes and PASMCs is significantly similar. Cellular lineage staining studies on NG2tdT mice in chronic hypoxia showed that tdT+ cells accumulate in muscularized arteries. RNAseq analysis performed on these hypoxic tdT+ cells demonstrated significant upregulation of SDF1, a chemokine involved in chemotaxis and angiogenesis. Compared to controls, SDF1 NG2-KO mice in chronic hypoxia had reduced RVSP, fulton index, less muscularization and lower abundance of NG2+ cells around microvessels (Fig. 1). In addition, SDF1 stimulation in human healthy pericytes induced greater contractility, impaired their capacity to establish endothelial-pericyte tube formation and increased expression of SMC markers SMA, Calponin and SM22. In contrast, SDF1 knockdown reduced PAH pericyte proliferation, contractility and improved endothelial cell tube formation on matrigel. Conclusions: SDF1 is upregulated in NG2+ mural cells. High expression of SDF1 could drive pericyte detachment and gain an SMC-like phenotype that contributes to abnormal muscularization and vascular obstruction. Targeting SDF1 could help prevent and reverse muscularization in PAH.
Abstract 13577: Human Induced Pluripotent Stem Cell-derived Cardiomyocyte Patches Ameliorate Right Ventricular Diastolic Dysfunction in a Rat Pressure-overloaded Right Heart Model
Authors: Takuji Watanabe, Shigeru Miyagawa, Akima Harada, Ai Kawamura, Takuji Kawamura, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2020)

Introduction: Right ventricular (RV) failure following definitive repair of congenital heart diseases (CHD) have great impact on survival after surgical intervention. Recently, human induced pluripotent stem cell-derived cardiomyocyte (hiPS-CM) sheet transplantation ameliorated left ventricular dysfunction in preclinical study, associating possible efficacy in RV failure of CHD. Hypothesis: We hypothesized whether hiPS-CM patch could improve distressed RV function in rat pressure overload model. Methods: F344/NJcl- rnu/rnu rat (7-9 weeks old, male, 180-210g) underwent pulmonary artery banding (PAB) via left thoracotomy under general anesthesia. Four weeks after PAB, hiPS-CM patch transplantation to the RV was performed in the hiPS-CM patch transplantation group (n = 10), whereas a sham operation was performed in the sham group (n =10). We evaluated for cardiac catheterization (CATH) data and pathological findings 8 weeks after PAB. Results: In CATH, RV end diastolic pressure (sham; 10.0 ± 4.1 vs hiPS-CM; 5.5 ± 2.7 mmHg, P &lt; 0.01), time constant of isovolumic relaxation (sham; 24.9 ± 8.6 vs hiPS-CM; 16.5 ± 6.4 ms, P &lt; 0.01) and end-diastolic pressure volume-relation (sham; 365.6 ± 246.3 vs hiPS-CM; 214.0 ± 147.4 mmHg/mL, P &lt;0.05) were significantly ameliorated in hiPS-CM group compared with sham group. Sirius-red staining showed a significant anti-fibrotic effects in the hiPS-CM group compared with the sham group (13.4 ± 5.3 vs 20.7 ± 4.8 %, P &lt;0.05). Factor VIII stain showed that myocardial capillary vascular density in the hiPS-CM group was significantly higher than in the sham group (640 ± 131 vs 362 ± 31 units/mm 2 , P &lt;0.001). hiPS-CMs were detectable on epicardium 2 weeks after hiPS-CM patch transplantation. The expression levels of vascular endothelial growth factor and hepatocyte growth factor in the hiPS-CM group was significantly higher than in the sham group (P &lt;0.05). Conclusions: In a rat model of a pressure-overload RV, hiPS-CM patch transplantation improved the diastolic function with suppressed ventricular fibrosis and increased capillary density, suggesting a promising treatment for RV failure in CHD patients after surgical repair.
Targeted delivery of siRNAs against hepatocellular carcinoma-related genes by a galactosylated polyaspartamide copolymer
Authors: Francesca Perrone, Emanuela Fabiola Craparo, Maja Cemazar, Urska Kamensek, Salvatore Emanuele Drago, Barbara Dapas, Bruna Scaggiante, Fabrizio Zanconati, Debora Bonazza, Mario Grassi, Nhung Truong, Gabriele Pozzato, Rossella Farra, Gennara Cavallaro, Gabriele Grassi
Journal: Journal of Controlled Release (2020)
Mammary tumor cells disseminate during atypical hyperplasia in Her2-transgenic mice
Authors: Yves Huesemann, Jochen B. Geigl, Falk Schubert, Manfred Meyer, Elke Burghart, Guido Forni, Roland Eils, Piero Musiani, Gert Riethmueller, Christoph A. Klein
Journal: Cancer Research (2006)

2399  It has been known for long that many patients with very small tumors will eventually succumb to their disease despite curative surgery. Moreover, up to 7% of cancer patients are diagnosed with cancer of unknown primary, i.e. metastasis in the absence of primary cancer. Interestingly, also for sporadic breast cancer clinical and experimental data point to dissemination of human breast cancer cells at a very early stage of tumor development. All these findings suggest that the popular linear progression model, predicting metastatic spread to occur late in disease progression, may not be applicable to all cancer patients. To address this question we analyzed systemic breast cancer progression in a model of human breast cancer, the Her-2 transgenic mouse from epithelial transformation to metastasis. BALB/c mice transgenic for the activated rat HER-2/neu closely mimic the progression and gene expression profiles of human breast cancer. We screened lungs and bone marrow samples of mice with antibody directed against the transgene Her-2 and additionally antibody against cytokeratin (CK) from various time points to assess the onset of metastatic spread. The isolated DNA of single cells, areas of primary tumors and of manifest pulmonary metastases was analyzed by comparative genomic hybridization (CGH). To our great surprise we detected metastatic cells in lung and bone marrow at a time when mammary glands showed histologically non-invasive atypical hyperplasia only but no tumors. We carefully analyzed primary lesions at this stage of disease by transmission electron microscopy and indeed observed tumor cells sneaking through the basement membrane. To confirm the malignant potential of early-disseminated cancer cells we performed bone marrow transplantation. Bone marrow from mice displaying only atypical hyperplasia was transplanted into wild-type siblings. Strikingly, transplantation of only 80 disseminated cancer cells resulted in bone marrow carcinosis in the recipient animals.These findings suggest that particular genetic changes in a permissive genetic background initiate systemic cancer early during carcinogenesis. Further analysis of Her2-transgenic mice may reveal mechanisms of metastatic spread that are at variance with conventional models but may explain many clinical courses observed in human cancer.
Abstract 17104: Utility of Screening Fetal Echocardiogram Following Normal Anatomy Ultrasound for In Vitro Fertilization Pregnancies
Authors: Rebecca Spurr, Jeffrey Conwell, Luciana T Young, Aarti Bhat, Mark Lewin, Bhawna Arya
Journal: Circulation (2020)

Introduction: In-vitro fertilization (IVF) is associated with a higher incidence of congenital heart disease (CHD), resulting in universal screening fetal echocardiograms (F-echo) even when obstetric scan (OB-scan), including cardiac structures is normal. Recent studies suggest that when OB-scan is normal, F-echo may add little benefit and increases cost and anxiety. We aim to determine the utility of screening F-echo in IVF pregnancies with normal cardiac anatomy on prior OB-scan. Methods: We conducted a retrospective chart review of IVF pregnancies referred for F-echo at the Seattle Children’s Hospital between 2014 and 2020. OB-scan results and subspecialty of interpreting physician (Obstetrics=OB; Maternal Fetal Medicine=MFM; Radiology=Rads), F-echos, and postnatal outcomes were reviewed. Cardiac anatomy on OB-scans was classified as complete if 4-chamber and outflow-tract views were obtained. Supplemental views (three-vessel and sagittal aortic arch views) on OB-scan were also documented. Results: Of 525 IVF referrals, 450 had normal F-echo. OB-scan reports were available for review in 411; 304 (74%) demonstrated normal cardiac anatomy and were interpreted by OB (42%), MFM (61%) and Rads (31%). F-echo was normal in 270 (88%). Of the 34 abnormal F-echo, none required intervention (16 muscular and 5 perimembranous ventricular septal defects, 9 minor valve abnormalities, 2 mild ventricular hypertrophy, 2 arrhythmia). There was no difference in OB-scan accuracy for identifying normal cardiac anatomy when comparing 4-chamber and outflow-tract views vs. addition of supplemental views (88% vs 90% normal F-echo; p&gt;0.1). Evaluation of OB-scan accuracy by interpreting physician subspecialty demonstrated normal F-echo in 93%, 80%, 91% read by OB, MFM and Rads, respectively. Conclusions: A majority of IVF referrals with normal cardiac anatomy visualized on OB-scan using 4-chamber and outflow-tract views resulted in normal F-echo, regardless of interpreting physician subspecialty or addition of supplemental views. Of the minority with abnormal F-echo, none required intervention. Consideration should be given to the cost/benefit of screening F-echo for the indication of IVF if normal cardiac anatomy is diagnosed on OB-scan.
Future directions in preclinical and translational cancer neuroscience research
Authors: Ihsan Ekin Demir, Carmen Mota Reyes, Wasfi Alrawashdeh, Güralp O. Ceyhan, Sylvie Deborde, Helmut Friess, Kıvanç Görgülü, Rouzanna Istvanffy, David Jungwirth, Rohini Kuner, Maria Maryanovich, Shorook Na’ara, Simon Renders, Jami L. Saloman, Nicole N. Scheff, Hendrik Steenfadt, Pavel Stupakov, Vera Thiel, Divij Verma, Bengi Su Yilmaz, Ruth A. White, Timothy C. Wang, Richard J. Wong, Paul S. Frenette, Ziv Gil, Brian M. Davis
Journal: Nature Cancer (2020)
Multi-locations evaluation of sorghum (Sorghum bicolor L.) genotypes for grain yield and yield related traits at western Oromia, Ethiopia
Authors: Biru Alemu, Geleta Negash, Wekgari Raga, Dereje Abera
Journal: Journal of Clinical Oncology (2020)

A field experiment was conducted on twelve sorghum genotypes against one local and two standard checks at Haro Sabu Agricultural Research Center (HSARC) sub sites for three consecutive years (2016-2018) using randomized completely block design (RCBD) to evaluate and select high yielding sorghum genotypes and to assess the impact of genotype by environmental interaction on grain yield and yield components across diverse growing environments of western Oromia. Eight agronomic traits and three economically important disease reaction were collected depending on the crop descriptor. Pooled over locations analysis of variance detected significance difference among tested genotypes for all collected traits. Genotype by environment interactions (G×E) significantly affected all recorded traits excluding days to heading and thousand seed weight. Genotype and genotype by environment interaction (GGE) bi-plot analysis revealed that G3, G11 and G12 as ideal genotypes in terms of yielding ability and stability and were promoted as candidates for possible release and use as genetic resource in future breeding programs.

	Key words: Sorghum bicolor L., Genotype by environment interactions (G×E), Genotype and genotype by environment interaction (GGE) bi-plot, stability.
Abstract 366: Association Between Attitudes and Preferences in Cardiopulmonary Resuscitation with Personality Traits in High-risk, Out-patient Healthcare Settings
Authors: Sabine Abukhadra, Tameen Jaara, Caroline Preston, Sachin Agarwal
Journal: Circulation (2020)

Background: Little is known about attitudes and preferences towards cardiopulmonary resuscitation (CPR) by outpatient healthcare employees. Investigations assessing the relationship between personality traits and willingness to perform CPR are few. Methods: From 10/2018-5/2019, the Columbia University Patient Safety Department partnered with the AHA to conduct training sessions on how to identify an individual in cardiac arrest and perform CPR at eight outpatient medical sites covering all major medical and surgical specialties (~1 million patient visits/year). Sites included did not have code teams and were in varying distances of the Emergency Department (ED). Participants, 80% of employees at each clinic, were surveyed on characteristics and motivation, as they apply to CPR, and completed the Ten-Item Personality Inventory (TIPI). Results: Of the 309 participants, 79% (244 of 309) were women and 32% (99 of 309) were Latinx. Before the investigation, 60% (185 of 309) of participants had learned CPR, but only 8.7% (27 of 309) of those individuals had refreshed their knowledge in the past year. About half, 46% (142 of 309), of participants, scored 6 or above (scale 0-7) on the openness personality trait and 77% (238 of 309) scored a 6 or above (scale 0-7) on the conscientiousness trait. More than half, 67% (207 of 309; CI 61-72) of participants claimed that harming others was a major concern in performing CPR at their practice. Participants with high openness scores were significantly less likely to cite their main concern during resuscitation as harm to the victim (p&lt;0.005). When asked of their willingness to perform CPR, 27% (83 of 309; CI 22-33) of participants cited various patient characteristics as deciding factors. Participants with high conscientiousness scores were significantly less likely to view any patient characteristics as critical in the debate to perform CPR (p&lt;0.0001). Conclusions: In out-patient healthcare offices, very few employees considered patient characteristics in their willingness to perform CPR; however, the majority are concerned that they will harm a patient by attempting to resuscitate. Future studies should look into the role of different personalities in willingness to perform CPR in a real-life setting.
Basophils and their effector molecules in allergic disorders
Authors: Kensuke Miyake, Sho Shibata, Soichiro Yoshikawa, Hajime Karasuyama
Journal: Allergy (2020)

Abstract Basophils are the rarest granulocytes which represent &lt;1% of peripheral blood leukocytes. Basophils bear several phenotypic similarities to tissue‐resident mast cells and therefore had been erroneously considered as blood‐circulating mast cells. However, recent researches have revealed that basophils play nonredundant roles in allergic inflammation, protective immunity against parasitic infections and regulation of innate and acquired immunity. Basophils are recruited to inflamed tissues and activated in an IgE‐dependent or IgE‐independent manner to release a variety of effector molecules. Such molecules, including IL‐4, act on various types of cells and play versatile roles, including the induction and termination of allergic inflammation and the regulation of immune responses. Recent development of novel therapeutic agents has enabled us to gain further insights into basophil biology in human disorders. In this review, we highlight the recent advances in the field of basophil biology with a particular focus on the role of basophils in allergic inflammation. Further studies on basophils and their effector molecules will help us identify novel therapeutic targets for treating allergic disorders.
Abstract 273: Implications of Expanding the Utstein Case Definition for Out of Hospital Cardiac Arrest
Authors: Jenny Shin, Richard Chocron, Thomas Rea, Peter Kudenchuk, Mickey Eisenberg, Bryan F McNally
Journal: Circulation (2020)

Background: The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized there being a system-specific survival correlation between the current Utstein and other VF populations inclusive of unwitnessed and EMS-witnessed VF OHCA that supports expanding performance metrics to this more comprehensive population that is more representative of the actual community burden of VF OHCA. Methods: We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated &gt;=100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used the Pearson coefficient to assess the correlation of agency-specific survival between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA. Results: A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7,774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between current the Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1-2, the Pearson correlation was 0.61. Conclusion: Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ~50%, while still achieving a distinguishing metric of system-specific performance.
Abstract 17042: CCL20 in Psoriasis: A Potential Biomarker of Disease Severity, Inflammation, and Impaired Vascular Health
Authors: Youssef A Elnabawi, Michael Tawil, Tessa Barrett, Edward A A Fisher, Jose Scher, Andrea Neimann, James Krueger, Jeffrey S Berger, Michael S Garshick
Journal: Circulation (2020)

Introduction: CV risk calculators that incorporate traditional risk factors underestimate CV risk in psoriasis and guidelines now suggest incorporating psoriasis into clinical decision making. Therefore, the purpose of this study is to use high throughput targeted proteomic panels to investigate the relationship between skin disease activity, inflammatory biomarkers, and vascular health. Methods: A targeted proteomics approach of 280 inflammatory proteins was performed in 23 psoriasis patients (age, mean [SD], 42 [14] years; 48% male, psoriasis area and severity index [PASI] 5 [3 - 11]) and 15 controls (41 [14], years; 53% male) recruited into an on-going clinical trial to assess vascular health in psoriasis (NCT03228017). Vascular health was assessed ex vivo through direct transcriptomic analysis of brachial vein endothelial cells. Serum samples were analyzed using the OLINK Proseek multiplex assay Inflammation I, Cardiovascular II/III profiles. Results: Targeted proteomics identified CCL20, IL6 and IL7A as the three highest circulating pro-inflammatory cytokines. CCL20 was 80% higher in psoriasis compared to controls ( p =0.004 ) and revealed a strong association with PASI ( r= 0.57; p =0.009). Additionally, CCL20 was positively associated with IL6, IL17A and hsCRP ( p &lt;0.01 for all). CCL20 positively associated with the mean composite transcriptome of endothelial inflammation (meanEC) (r=0.55, p&lt;0.01), which remained significant even after adjustment for traditional CV risk factors (adjusted [adj]β=0.63, p =0.001). Interestingly, CCL20 had a stronger correlation with meanEC than other established pro-inflammatory makers, including IL6 (adj β=0.48, p =0.04), IL17a (adj β=0.54, p =0.05), TNFα (adj β=0.06, p =0.78), and hsCRP (adj β=0.08, p =0.79). In nested models CCL20 added value (χ 2 = 79.22, p&lt;0.001) to a model already incorporating PASI, Framingham Risk, hs-CRP, IL-17A and IL-6 (χ 2 = 48.18, p&lt;0.001). Conclusions: We demonstrate that CCL20 expression has a strong correlation with PASI score and endothelial inflammation and reflects systemic inflammation better than well-established markers of inflammation in psoriasis including IL-6, IL-17A, and hs-CRP. CCL20 may serve as a potential biomarker of vascular health in this population.
Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 Years
Authors: Lindsey C. Yourman, Irena S. Cenzer, W. John Boscardin, Brian T. Nguyen, Alexander K. Smith, Mara A. Schonberg, Nancy L. Schoenborn, Eric W. Widera, Ariela Orkaby, Annette Rodriguez, Sei J. Lee
Journal: JAMA Internal Medicine (2020)

Guidelines recommend targeting preventive interventions toward older adults whose life expectancy is greater than the intervention's time to benefit (TTB). The TTB for statin therapy is unknown.