bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repair of Anomalous Right Coronary Artery From the Pulmonary Artery Using the Modified Trapdoor Technique
Authors: Ganta Srujan , Vanderploeg Megan , Kavarana Minoo 
Published: March 2019

Background: Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is rare. Unique anatomical characteristics observed include tethering secondary to the extensive collateral vessels, severe native coronary tortuosity, and massive dilation of the coronary arteries. This requires specific technical consideration to ensure safe translocation. Methods: A single-center retrospective review of six patients with ARCAPA was performed. Echocardiographic and computerized tomography scan data were analyzed for anatomical and functional cardiac characteristics. Operative techniques were analyzed, which reflected an evolution toward a modified-trapdoor technique. Results: Five children presented with asymptomatic murmurs and one adult patient with unstable angina. All patients underwent successful surgical correction. The modified trapdoor technique provided the most ideal geometry for coronary transfer secondary to its anatomical characteristics. Two patients had coronary button transfers above the sinotubular junction using vertical stab incisions, one had the button implanted after excising part of the aortic wall, and last three patients had modified trapdoor incisions. Mean cardiopulmonary bypass and cross-clamp times were 170 ± 27 minutes and 99.5 ± 29 minutes respectively. The average hospital stay was five days and there were no mortalities. Conclusions: Anomalous right coronary from the pulmonary artery’s unique anatomical characteristics require a coronary transfer technique different from that performed in aortic root replacement. In some respects, our modified technique resembles coronary transfers used in difficult arterial switch operations. The use of a modified trapdoor incision simplifies coronary transfer and may minimize coronary kinking and subsequent complications related to coronary transfer.
The Congenital Heart Technical Skill Study: Rationale and Design
Authors: Anderson Brett R. , Kumar S. Ram , Gottlieb-Sen Danielle , Liava’a Matthew H. , Hill Kevin D. , Jacobs Jeffrey P. , Moga Francis X. , Overman David M. , Newburger Jane W. , Glied Sherry A. , Bacha Emile A. ,   on behalf of the Congenital Heart Technical Skill Study
Published: March 2019

Background: We report the rationale and design for a peer-evaluation protocol of attending congenital heart surgeon technical skill using direct video observation. Methods: All surgeons contributing data to The Society of Thoracic Surgeons—Congenital Heart Surgery Database (STS-CHSD) are invited to submit videos of themselves operating, to rate peers, or both. Surgeons may submit Norwood procedures, complete atrioventricular canal repairs, and/or arterial switch operations. A HIPPA-compliant website allows secure transmission/evaluation. Videos are anonymously rated using a modified Objective Structured Assessment of Technical Skills score. Ratings are linked to five years of contemporaneous outcome data from the STS-CHSD and surgeon questionnaires. The primary outcome is a composite for major morbidity/mortality. Results: Two hundred seventy-six surgeons from 113 centers are eligible for participation: 83 (30%) surgeons from 53 (45%) centers have agreed to participate, with recruitment ongoing. These surgeons vary considerably in years of experience and outcomes. Participants, both early and late in their careers, describe the process as “very rewarding” and “less time consuming than anticipated.” An initial subset of 10 videos demonstrated excellent interrater reliability (interclass correlation = 0.85). Conclusions: This study proposes to evaluate the technical skills of attending pediatric cardiothoracic surgeons by video observation and peer-review. It is notable that over a quarter of congenital heart surgeons, across a range of experiences, from almost half of United States centers have already agreed to participate. This study also creates a mechanism for peer feedback; we hypothesize that feedback could yield broad and meaningful quality improvement.
Xenon-129 MRI detects ventilation deficits in paediatric stem cell transplant patients unable to perform spirometry
Authors: Walkup Laura L. , Myers Kasiani , El-Bietar Javier , Nelson Adam , Willmering Matthew M. , Grimley Michael , Davies Stella M. , Towe Christopher , Woods Jason C. 
Published: March 2019

BackgroundEarly detection of pulmonary morbidity following haematopoietic stem cell transplantation (HSCT) remains an important challenge for intervention, primarily due to the insensitivity of spirometry to early change, and in paediatrics, patient compliance provides additional challenges. Regional lung ventilation abnormalities in paediatric HSCT patients were quantified using hyperpolarised xenon-129 (129Xe) magnetic resonance imaging (MRI) and compared to spirometry.MethodsMedically stable, paediatric allogeneic HSCT patients (n=23, ages 6–16 years) underwent an outpatient MRI scan where regional ventilation was quantified with a breath-hold of hyperpolarised129Xe gas. Ventilation deficits, regions of the lung that ventilate poorly due to obstruction, were quantified as a ventilation defect percentage (VDP) and compared to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio, and forced expiratory flow at 25–75% of FVC (FEF25–75%) from spirometry using linear regression.ResultsThe mean±sd129Xe VDP was 10.5±9.4% (range 2.6–41.4%).129Xe VDP correlated with FEV1, FEV1/FVC ratio and FEF25–75%(p≤0.02 for all comparisons). Ventilation deficits were detected in patients with normal spirometry (i.e.FEV1>80%), supporting the sensitivity of129Xe MRI to early obstruction reported in other pulmonary conditions. Seven (30%) patients could not perform spirometry, yet ventilation deficits were observed in five of these patients, detecting abnormalities that otherwise may have gone undetected and untreated until advanced.ConclusionLung ventilation deficits were detected using hyperpolarised129Xe gas MRI in asymptomatic paediatric HSCT patients and in a subgroup who were unable to perform reliable spirometry.129Xe MRI provides a reliable imaging-based assessment of pulmonary involvement in this potentially difficult to diagnose paediatric population.
Reconstruction of evolutionary trajectories of chromosomes unraveled independent genomic repatterning between Triticeae and Brachypodium
Authors: Wang Zhenyi , Wang Jinpeng , Pan Yuxin , Lei Tianyu , Ge Weina , Wang Li , Zhang Lan , Li Yuxian , Zhao Kanglu , Liu Tao , Song Xiaoming , Zhang Jiaqi , Yu Jigao , Hu Jingjing , Wang Xiyin 
Published: March 2019

Abstract
Background
After polyploidization, a genome may experience large-scale genome-repatterning, featuring wide-spread DNA rearrangement and loss, and often chromosome number reduction. Grasses share a common tetraploidization, after which the originally doubled chromosome numbers reduced to different chromosome numbers among them. A telomere-centric reduction model was proposed previously to explain chromosome number reduction. With Brachpodium as an intermediate linking different major lineages of grasses and a model plant of the Pooideae plants, we wonder whether it mediated the evolution from ancestral grass karyotype to Triticeae karyotype.

Results
By inferring the homology among Triticeae, rice, and Brachpodium chromosomes, we reconstructed the evolutionary trajectories of the Triticeae chromosomes. By performing comparative genomics analysis with rice as a reference, we reconstructed the evolutionary trajectories of Pooideae plants, including Ae. Tauschii (2n = 14, DD), barley (2n = 14), Triticum turgidum (2n = 4x = 28, AABB), and Brachypodium (2n = 10). Their extant Pooidea and Brachypodium chromosomes were independently produced after sequential nested chromosome fusions in the last tens of millions of years, respectively, after their split from rice. More frequently than would be expected by chance, in Brachypodium, the ‘invading’ and ‘invaded’ chromosomes are homoeologs, originating from duplication of a common ancestral chromosome, that is, with more extensive DNA-level correspondence to one another than random chromosomes, nested chromosome fusion events between homoeologs account for three of seven cases in Brachypodium (P-value≈0.00078). However, this phenomenon was not observed during the formation of other Pooideae chromosomes.

Conclusions
Notably, we found that the Brachypodium chromosomes formed through exclusively distinctive trajectories from those of Pooideae plants, and were well explained by the telomere-centric model. Our work will contribute to understanding the structural and functional innovation of chromosomes in different Pooideae lineages and beyond.
Young pregnant women and risk for mental disorders: findings from an early pregnancy cohort
Authors: Lockwood Estrin Georgia , Ryan Elizabeth G. , Trevillion Kylee , Demilew Jill , Bick Debra , Pickles Andrew , Howard Louise Michele 
Published: March 2019

BackgroundYoung women aged 16–24 are at high risk of common mental disorders (CMDs), but the risk during pregnancy is unclear.AimsTo compare the population prevalence of CMDs in pregnant women aged 16–24 with pregnant women ≥25 years in a representative cohort, hypothesising that younger women are at higher risk of CMDs (depression, anxiety disorders, post-traumatic stress disorder, obsessive–compulsive disorder), and that this is associated with low social support, higher rates of lifetime abuse and unemployment.MethodAnalysis of cross-sectional baseline data from a cohort of 545 women (of whom 57 were aged 16–24 years), attending a South London maternity service, with recruitment stratified by endorsement of questions on low mood, interviewed with the Structured Clinical Interview DSM-IV-TR.ResultsPopulation prevalence estimates of CMDs were 45.1% (95% CI 23.5–68.7) in young women and 15.5% (95% CI 12.0–19.8) in women ≥25, and for ‘any mental disorder’ 67.2% (95% CI 41.7–85.4) and 21.2% (95% CI 17.0–26.1), respectively. Young women had greater odds of having a CMD (adjusted odds ratio (aOR) = 5.8, 95% CI 1.8–18.6) and CMDs were associated with living alone (aOR = 3.0, 95% CI 1.1–8.0) and abuse (aOR = 1.5, 95% CI 0.8–2.8).ConclusionsPregnant women between 16 and 24 years are at very high risk of mental disorders; services need to target resources for pregnant women under 25, including those in their early 20s. Interventions enhancing social networks, addressing abuse and providing adequate mental health treatment may minimise adverse outcomes for young women and their children.Declaration of interestNone.
Validation of MSKCC pre-prostatectomy nomogram in men who undergo MRI-targeted prostate biopsy prior to radical prostatectomy.
Authors: Glaser Zachary A , Gordetsky Jennifer , Bae Sejong , Nix Jeffrey , Porter Kristin K , Rais-Bahrami Soroush 
Published: March 2019

14 Background: The Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Prostatectomy nomogram is a widely used resource using clinical factors to predict the likelihood of adverse pathology at radical prostatectomy. The increasing adoption of magnetic resonance imaging (MRI) and MRI-targeted biopsy (TB) permits optimized detection of clinically-significant cancer over systematic biopsy sampling alone. We aim to validate the prognostic utility of the MSKCC Pre-Prostatectomy nomogram with TB pathology results. Methods: Men who underwent systematic extended-sextant prostate biopsy (SB) followed by MRI TB who later underwent radical prostatectomy at our institution were included. Patient information was entered into the MSKCC Pre-Prostatectomy nomogram using five biopsy reporting schemes (SB alone, TB alone reported each of two ways (individual core (IC) technique or aggregate cores (AG) technique combining cores from a single MRI targeted lesion), and SB with TB combined with TB reported by both IC and AG methods. The likelihood of extracapsular extension (EPE), lymph node involvement (LNI), and seminal vesicle invasion (SVI) as predicted by the nomogram for each biopsy reporting schema were compared to radical prostatectomy pathology. Results: We identified 63 men from January 2014 to November 2017. On ROC analysis, IC-TB, AG-TB, SB plus IC-TB, and SB plus AG-TB exhibited similar, if not improved, AUC compared to SB alone in predicting EPE (0.671, 0.674, 0.658, and 0.6613 versus 0.6085). For LNI, superior AUC was observed for AG-TB (0.647) compared to IC-TB (0.571) and SB alone (0.524) Equivocal SVI prediction was observed for SB plus IC-TB compared to SB alone (0.727 versus 0.733). Conclusions: Using TB pathology results either alone or combined with SB pathology results for the MSKCC Pre-Prostatectomy nomogram appears comparable, if not improved, in prognosticating adverse pathologic features on radical prostatectomy compared to using SB core data alone from which the nomogram was developed.
Initial results from a phase II study of nivolumab (NIVO) plus ipilimumab (IPI) for the treatment of metastatic castration-resistant prostate cancer (mCRPC; CheckMate 650).
Authors: Sharma Padmanee , Pachynski Russell Kent , Narayan Vivek , Flechon Aude , Gravis Gwenaelle , Galsky Matt D. , Mahammedi Hakim , Patnaik Akash , Subudhi Sumit Kumar , Ciprotti Marika , Duan Tao , Saci Abdel , Hu Sarah , Han G. Celine , Fizazi Karim 
Published: March 2019

142 Background: Immune checkpoint inhibitor monotherapy has shown limited clinical benefit in patients (pts) with prostate cancer, likely due to an immunologically “cold” tumor microenvironment. We report preplanned interim efficacy/safety for NIVO + IPI in pts with mCRPC from CheckMate 650. Methods: Asymptomatic/minimally symptomatic pts who progressed after 2nd-generation hormone therapy and have not received chemotherapy for mCRPC (cohort 1) and pts who progressed after taxane-based chemotherapy (cohort 2) were included. Treatment was NIVO 1 mg/kg + IPI 3 mg/kg Q3W for 4 doses, then NIVO 480 mg every 4 weeks. Coprimary endpoints: objective response rate (ORR) and radiographic PFS per PCWG2. Safety is a secondary endpoint. Exploratory endpoints include correlation of biomarkers with efficacy. Results: 78 pts had a minimum follow-up of 6 months; among pts with baseline measurable disease, ORR was 26% and 10% in cohorts 1 and 2 (Table). In both cohorts, ORR was higher in pts with PD-L1 ≥1%, DNA damage repair (DDR), homologous recombination deficiency (HRD), or above-median tumor mutational burden (TMB). Of all PSA responding pts (Table), 4 had PSA <0.2 ng/mL. Grade 3–4 treatment-related adverse events occurred in 39% and 51% of pts in cohorts 1 and 2; one grade 5 event occurred in each cohort. Conclusions: In a malignancy where immune checkpoint inhibitor monotherapy has previously shown limited success, NIVO + IPI demonstrated activity in pretreated pts with mCRPC, particularly in a biomarker-enriched population, with a safety profile consistent with this dosing schedule. Further study is warranted. Clinical trial information: NCT02985957. [Table: see text]
Assessment of circulating tumor cell number as a transitional surrogate endpoint for survival in phase II trials for metastatic castration-resistant prostate cancer.
Authors: Scher Howard I. , Mccormack Robert Thomas , Molina Arturo , Smith Matthew Raymond , Dreicer Robert , Saad Fred , De Wit Ronald , Fizazi Karim , Aftab Dana T. , Limon Ana , Fleisher Martin , De Bono Johann S. , Kelloff Gary J. , Heller Glenn 
Published: March 2019

143 Background: Short-term measures of response that reflect clinical benefit are a critical unmet need for clinical trials for mCRPC. Using data from 5 randomized mCRPC trials, we showed that a response endpoint (RE) based on a change in CTC number using the FDA cleared CellSearch® (Menarini) platform from any, (≥ 1, CTC any) to 0 (CTC0) per 7.5 ml of blood was associated strongly with overall survival (OS). Here we explored whether different CTC and PSA REs could serve as “transitional surrogates” defined as a biomarker validated in phase 2 but not in phase 3 trials for overall survival (OS), using the baseline and week 13 prostate-specific antigen (PSA) level and CTC counts. Methods: Four 13-week REs were studied: (i) PSA50 (≥ 50% PSA decline from baseline), (ii) CTC0 (≥ 1 CTC/7.5 ml of blood at baseline and 0 CTCs at week 13), (iii) both PSA50 and CTC0, and (iv) either PSA50 or CTC0. The relative effectiveness of these REs as transitional surrogates for OS was evaluated at the patient level by discrimination, the separation between responder and non-responder survival curves, and at the trial level using explained variation, the accuracy in predicting k-month survival in a trial with the response proportion. Results: A total of 6081 pts were enrolled of whom 5660 (93%) survived until week 13 and among these patients 3080 (54%) had a baseline CTC count ≥ 1 and baseline PSA ≥ 5 ng/ml. At the patient level, separation between responder and non-responder survival curves over time was greater using CTC0 than PSA50 (average difference in survival probability 0.35 vs. 0.29, respectively). At the trial level, explained variation in survival over time was also greater for CTC0 than PSA50 (average R-squared 0.67 vs. 0.58, respectively). CTC/PSA combination REs did not improve on CTC0 at either level. Conclusions: The CTC0 RE provides stronger discrimination than PSA50 at the patient level and greater observed explained variation at the trial level. The results suggest that for the individual patient, a decrease in CTCs to zero at week 13 is a stronger indicator of longer term OS than the more widely used PSA50 and serves as a reasonably likely surrogate for OS in clinical trials.
Targeting mediator subunits CDK8/CDK19 for treatment of advanced prostate cancer.
Authors: Hupe Marie C. , Offermann Anne , Becker Finn , Joerg Vincent , Vogel Wenzel , Braegelmann Johannes , Perner Sven , Merseburger Axel Stuart 
Published: March 2019

152 Background: The mediator complex plays a pivotal role in the regulation of gene transcription. The subunits CDK8 and CDK19 are overexpressed in advanced prostate cancer (PCa) and promote migration and invasion, as shown previously by our group. The aim of this study was to analyze if CDK8/CDK19 inhibition can impede PCa progression. Methods: Immunohistochemistry for CDK8 and CDK19 was performed on a large PCa cohort (376 radical prostatectomy (RP) specimens, 39 locally advanced tumors, 32 lymph node metastases, 24 distant metastases, 73 benign prostatic specimens). PCa cell lines (DU145, PC3) were treated with CDK8/CDK19 small molecule inhibitors followed by MTT assay, wound healing assay, and Western Blot for epithelial/mesenchymal markers. Results: CDK19 is higher expressed in primary PCa vs. benign specimens and locally advanced PCa/distant metastases vs. primary PCa. CDK8 and CDK19 are higher expressed in castration-resistant specimens vs. hormone-naive specimens. CDK19 significantly correlates with grade group in RP specimens. Biochemical recurrence free survival rates are lower for patients with high vs. medium vs. no/low CDK19 expression in the tumor. CDK19 predicts recurrence free survival independently from grade group and PSA. CDK8/CDK19 inhibition results in decreased migration, while there is no effect on proliferation. Mesenchymal markers are reduced while epithelial markers are induced following CDK8/CDK19 inhibition. Conclusions: CDK19 qualifies as a prognostic marker predicting biochemical recurrence following RP. CDK8/CDK19 inhibition leads to decreased migratory potential and mesenchymal phenotype. CDK8/19 expression increases during progression to castration-resistance. Collectively, CDK8/CDK19 represents a new target for treatment of advanced and/or castration-resistant PCa.
A circulating tumor cell RNA assay for dynamic assessment of androgen receptor signaling inhibitors sensitivity in metastatic castration-resistant prostate cancer.
Authors: Jan Yu Jen , Yoon Junhee , Chen Jie-Fu , Chen Pin-Jung , Teng Pai-Chi , Yao Nu , Cheng Shirley , Lozano Amber , Freeman Michael , You Sungyong , Tseng Hsian-Rong , Posadas Edwin M. 
Published: March 2019

157 Background: Tissue-based gene signatures can predict clinical behavior in prostate cancer (PC). Our objective was to extend their application to circulating tumor cells (CTCs) and to show that changes in the signature were associated with changes in clinical behavior. Methods: Our approach combined the Thermoresponsive(TR)-NanoVelcro CTC purification system with the Nanostring nCounter system for cellular purification and transcriptomic analysis. The Prostate Cancer Classification System (PCS) panel was modified for use in CTCs. We selected 31 blood samples from 23 PC patients receiving androgen receptor signaling inhibitors (ARSI) and measured the PCS1 Z score (probability). These findings were compared with clinical outcome data (responsiveness/resistance). Results: A modified, 16-gene PCS1 signature was established and validated through a rigorous bioinformatics process. We performed analytical validation of our combined CTC-RNA system to ensure reproducibility and specificity. In patient bloods, ARSI-resistant samples (ARSI-R, n = 14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n = 17) (Rank-sum test, P = 0.003). The analyzed bloods contained samples from 8 patients who developed resistance to an ARSI allowing for dynamic measurement of gene expression. Our analysis found that the PCS1 Z score increased at the time that ARSI-resistance emerged (Pairwise T-test, P = 0.016). Conclusions: Using this new methodology, contemporary, clinically-relevant gene signatures such as PCS could be measured non-invasively in CTCs. These findings can be used to relate gene expression to clinical drug response. This approach also allowed for measurement of dynamic variations of gene expression in individual patients over time that correlated to ARSI sensitivity.
A Genome-wide association study of metastatic prostate cancer.
Authors: Teerlink Craig , Hahn Andrew W , Esther John , Rathi Nityam , Farnham James M , Agarwal Neeraj , Cannon-Albright Lisa 
Published: March 2019

160 Background: There are no biomarkers currently used in clinical practice that can predict which men will develop metastatic prostate cancer (mPrCa). Germline genetic variants that are highly associated with metastatic disease could be used for such prediction and may be identifiable from genome-wide association analyses (GWAS) conducted in appropriately scaled mPrCa case-control datasets. Methods: 451 mPrCa cases sequentially sampled from University of Utah/Huntsman Cancer Institute clinics were genotyped on the Illumina OmniExpress SNP platform and population-matched via principal components analysis to 1043 controls from dbGaP study phs000733 genotyped on the Illumina 5M SNP platform. The mPrCa cases and controls were analyzed via genome-wide association to identify SNPs highly associated with mPrCa. The dataset was then merged and re-analyzed with 176 lethal prostate cancer cases (identified in the Utah SEER Tumor Registry with a linked Utah death certificate including prostate cancer as a cause of death) in an attempt to identify a larger number of potential candidate SNPs associated with metastatic or lethal prostate disease. Results: The GWAS of mPrCa cases identified 4 significant SNPs at the 8q24.21 locus (p < 5e-8), as well as 9 SNPs in 6 previously unreported regions (5q14.1, 6p24.1, 8q21.3, 15q13.3, 15q22.2, and 17q25.1) with suggestive evidence for association (p < 1e-6). In addition, 30 SNPs with nominal evidence (p < 0.001) in the mPrCa-only GWAS appeared with more extreme p-values when the 176 lethal subjects were included in the analysis, and may be appropriate candidate variants to test in external datasets. Conclusions: In this case-control GWAS study of 627 men with mPrCa or lethal PrCa, germline SNPs at the 8q24.21 locus and 6 previously unreported regions may be associated with mPrCa. These findings should be validated in external datasets of men with mPrCa.