bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD6-01: Prevalence of PDL1 and tumor infiltrating lymphocytes (TILs) in primary and metastatic TNBC
Authors: Li Y , Chang C-W , Tran D , Denker M , Hegde P , Molinero L 
Published: February 2018

Abstract
Background: Metastatic Triple Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype with a high unmet medical need and limited therapeutic options. PDL1 on immune cells (IC) and TILs were associated with activity to the anti-PDL1 mAB atezolizumab in mTNBC (Schmid AACR 2017). PDL1 IC &gt;=1% is the diagnostic hypothesis for TNBC atezolizumab studies. The goal of the current project was to evaluate the prevalence of PDL1 and TILs in primary and metastatic TNBC samples.
Methods: FFPE tumor tissue from pathology documented TNBC tissues were centrally tested for PDL1 IHC on tumor cells (TC) and infiltrating immune cells (IC) (VENTANA SP142 assay) and quantified as percentage of tumor area. TILs were evaluated as a percentage of tumor area and PD-L1 gene (CD274) expression was quantified by Fluidigm.
Results: 669 tumors were evaluable for PD-L1 by IHC and TILs. 280 samples were annotated as primary tumors and 179 as metastases with 210 denoted as unknown. PDL1 IC and TC immunostaining was correlated to PD-L1 transcript expression (r = 0.55 and r = 0.51, respectively). 84% of samples had no tumor cells expressing PDL1 and 16% had at least 1% of PDL1 in TC. 44% of the samples had no PDL1 in the immune cells, 35% expressed PDL1 IC [31% to &lt;5%] and 21% PDL1 IC 35%. PDL1 distribution was similar between primary and metastases, with median of 1% and 0% for PDL1 IC and TC, respectively. Analyses of anatomical locations suggest that PDL1 IC is highest in lymph nodes (median IC = 3%), lowest in liver metastases (median IC = 0.5%) while breast tissue is intermediate (median IC = 1%). The correlation between PDL1 IC and TILs is r = 0.69. TILs were numerically higher in primary compared to metastases (10% vs 5%). Anatomical TIL distribution confirmed liver metastases as least infiltrated, while breast, lymph node and lung metastases with similarly higher values (5% vs 10%, respectively). Concordance analyses in intra-individual synchronous and asynchronous matched pairs were performed at a cutoff of PDL1 IC 31%. Concordance of matched specimens was 82% in 11 synchronous pairs and 75% in 20 asynchronous pairs.
Conclusions: Prevalence of PDL1 IHC is similar between primary and metastatic TNBC samples. Although PDL1 IC and TILs are highly correlated, TILs are less prevalent in metastases compared to primary tissue. Anatomical location may influence prevalence of both PDL1 IC and TILs. Concordance of PDL1 in matched pairs is high, suggesting PDL1 IC may be a stable biomarker.
Citation Format: Li Y, Chang C-W, Tran D, Denker M, Hegde P, Molinero L. Prevalence of PDL1 and tumor infiltrating lymphocytes (TILs) in primary and metastatic TNBC [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD6-01.
Abstract PL2: Advances in the understanding and the applications of mutational signatures in human cells
Authors: Nik-Zainal S 
Published: February 2018

Abstract
A cancer genome is an historical account of the mutagenic activity that has occurred throughout the development of the tumour. Indeed, every mutation matters. While driver mutations were the main focus of cancer research for a long time, passenger mutational signatures, the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis, are also biologically informative.
We previously outlined the methods for identifying and quantifying base substitution mutational signatures present in primary human cancers. Recently, the intellectual framework of mutational signatures was extended to include six novel rearrangement signatures. Exploring this in &gt;2,500 whole genome sequenced tumours of multiple tumour types, reveals how our early (and rather simplistic) thinking of mutational signatures, requires critical re-evaluation. There are more nuances than previously appreciated.
Diving into the detail of individual mutational signatures, we reveal intriguing mechanistic insights into the DNA damage and repair processes that mark the landscape of cancer genomes. In some instances, our findings invite more thoughtful consideration of that relatively binary distinction between drivers and passengers. Furthermore, we demonstrate why our whole genome profiling methods could assist in taking things to a clinical level, with mutational signatures forming an additional weapon in the arsenal of cancer diagnostics and therapeutic stratification, in the modern war against cancer.
Finally, we validate cancer mutational signatures using cell-based model systems and arrive at new realisations (unpublished). This powerful approach (humbles the analyst and) emphasises how biological exploration of big data still relies indispensably on experimental work to truly advance understanding.
Citation Format: Nik-Zainal S. Advances in the understanding and the applications of mutational signatures in human cells [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PL2.
Bempedoic Acid Lowers Low-Density Lipoprotein Cholesterol and Attenuates Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient (
LDLR
+/−
and
LDLR
−/−
) Yucatan Miniature Pigs
Authors: Burke Amy C. , Telford Dawn E. , Sutherland Brian G. , Edwards Jane Y. , Sawyez Cynthia G. , Barrett P. Hugh R. , Newton Roger S. , Pickering J. Geoffrey , Huff Murray W. 
Published: February 2018

Objective—
Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia.

Approach and Results—

Gene targeting has been used to generate Yucatan miniature pigs heterozygous (
LDLR
+/−
) or homozygous (
LDLR
−/−
) for LDL receptor deficiency (ExeGen).
LDLR
+/−
and
LDLR
−/−
pigs were fed a high-fat, cholesterol-containing diet (34% kcal fat; 0.2% cholesterol) and orally administered placebo or BemA for 160 days. In
LDLR
+/−
pigs, compared with placebo, BemA decreased plasma cholesterol and LDL-C up to 40% and 61%, respectively. In
LDLR
−/−
pigs, in which plasma cholesterol and LDL-C were 5-fold higher than in
LDLR
+/−
pigs, BemA decreased plasma cholesterol and LDL-C up to 27% and 29%, respectively. Plasma levels of triglycerides and high-density lipoprotein cholesterol, fasting glucose and insulin, and liver lipids were unaffected by treatment in either genotype. In the aorta of
LDLR
+/−
pigs, BemA robustly attenuated en face raised lesion area (−58%) and left anterior descending coronary artery cross-sectional lesion area (−40%). In
LDLR
−/−
pigs, in which lesions were substantially more advanced, BemA decreased aortic lesion area (−47%) and left anterior descending coronary artery lesion area (−48%).

Conclusions—

In a large animal model of LDLR deficiency and atherosclerosis, long-term treatment with BemA reduces LDL-C and attenuates the development of aortic and coronary atherosclerosis in both
LDLR
+/−
and
LDLR
−/−
miniature pigs.
Comparison Between Different Strategies of Rheumatic Heart Disease Echocardiographic Screening in Brazil: Data From the PROVAR (Rheumatic Valve Disease Screening Program) Study
Authors: Nascimento Bruno R. , Sable Craig , Nunes Maria Carmo P. , Diamantino Adriana C. , Oliveira Kaciane K. B. , Oliveira Cassio M. , Meira Zilda Maria A. , Castilho Sandra Regina T. , Santos Júlia P. A. , Rabelo Letícia Maria M. , Lauriano Karlla C. A. , Carmo Gabriel A. L. , Tompsett Allison , Ribeiro Antonio Luiz P. , Beaton Andrea Z. , Lauar Amanda O. , Costa Ana Luísa M. , Ferreira Camila G. , Webb Catherine L. , Lopes Eduardo L. V. , Ruiz Gabriela Z. L. , Chequer Graziela , Richards Hedda , Castro Iara M. , Teixeira Isabella M. , Perlman Lindsay , Lafeta Luciana C. X. , Barros Luise Cristina T. R. , Galbas Michelle C. , Lourenço Tainá V. , de Rezende Vitória M. L. R. 
Published: February 2018

Background

Considering the limited accuracy of clinical examination for early diagnosis of rheumatic heart disease (
RHD
), echocardiography has emerged as an important epidemiological tool. The ideal setting for screening is yet to be defined. We aimed to evaluate the prevalence and pattern of latent
RHD
in schoolchildren (aged 5–18 years) and to compare effectiveness of screening between public schools, private schools, and primary care centers in Minas Gerais, Brazil.

Methods and Results

The
PROVAR
(Rheumatic Valve Disease Screening Program) study uses nonexperts and portable and handheld devices for
RHD
echocardiographic screening, with remote interpretation by telemedicine, according to the 2012 World Heart Federation criteria. Compliance with study consent and prevalence were compared between different screening settings, and variables associated with
RHD
were analyzed. In 26 months, 12 048 students were screened in 52 public schools (n=10 901), 2 private schools (n=589), and 3 primary care centers (n=558). Median age was 12.9 years, and 55.4% were girls. Overall
RHD
prevalence was 4.0% borderline (n=486) and 0.5% definite (n=63), with statistically similar rates between public schools (4.6%), private schools (3.5%), and primary care centers (4.8%) (
P
=0.24). The percentage of informed consents signed was higher in primary care centers (84.4%) and private schools (66.9%) compared with public schools (38.7%) (
P
<0.001). Prevalence was higher in children ≥12 years (5.3% versus 3.1%;
P
<0.001) and girls (4.9% versus 4.0%;
P
=0.02). Only age (odds ratio, 1.12; 95% confidence interval, 1.09–1.17;
P
<0.001) was independently associated with
RHD
.

Conclusions

RHD
screening in primary care centers seems to achieve higher coverage rates. Prevalence among schoolchildren is significantly high, with rates higher than expected in private schools of high‐income areas. These data are important for the formulation of public policies to confront
RHD
.
A Fluctuation–Dissipation Relation for the Ocean Subject to Turbulent Atmospheric Forcing
Authors: Wirth Achim 
Published: February 2018

AbstractThe fluctuation–dissipation relation for a turbulent fluid layer (ocean) subject to frictional forcing by a superposed lighter fluid layer (atmosphere) in local models of air–sea dynamics is established. The fluctuation–dissipation relation reflects the fact that air–sea interaction not only injects energy in the ocean but also dissipates it. Energy injection and dissipation must therefore be related. The competition between the two processes determines the oceanic energy budget in the idealized dynamics considered here. When applying the fluctuation–dissipation relation to a two-dimensional, two-layer, Navier–Stokes model with turbulent dynamics, in the atmosphere and the ocean, coupled by a quadratic friction law, the friction parameter is estimated within 8% of the true value, while the estimation of the mass ratio between the atmosphere and the ocean fails, as the forcing time scale is not faster than the characteristic time scale of the atmospheric dynamics.
Correlation between epicardial fat thickness and aortic valve sclerosis
Authors: Nabati Maryam , Favaedi Maryam , Kheirgoo Masoud , Yazdani Jamshid , Dabirian Mozhdeh 
Published: February 2018

Background Epicardial fat is a true visceral fat deposit with adverse effects through the secretion of numerous proinflammatory and proatherogenic cytokines. Previous studies showed an association between aortic valve sclerosis and coronary artery disease. The aim of this study was to determine the correlation between epicardial fat thickness and aortic valve sclerosis. Method The study involved 225 patients who were admitted for coronary angiography due to new-onset angina. They underwent transthoracic echocardiography and epicardial fat thickness was determined. The sclerosis scoring of each aortic cusp, average aortic valve sclerosis score index, and left ventricular ejection fraction were determined. The variables of left ventricular diastolic function obtained included the early diastolic velocity determined by transmitral pulsed Doppler, and early mitral annular velocity measured by tissue Doppler. Results Patients with an epicardial fat thickness ≥7 mm were older ( p = 0.006), with more hypertension ( p = 0.045) and hyperlipidemia ( p < 0.001). Their average aortic valve sclerosis score index was higher (1.4 ± 1.02 vs. 0.86 ± 0.85, p = 0.001), and left ventricular ejection fraction and early mitral annular velocity were lower ( p < 0.001 and 0.03, respectively). They also exhibited more left ventricular hypertrophy ( p = 0.026) and a trend towards more significant coronary artery disease and 3-vessel disease ( p = 0.086 and 0.073, respectively). Conclusion Our findings confirm that epicardial fat as a marker of visceral adipose tissue may have an important role in promoting inflammatory and atherosclerotic changes in the aortic valve.
The role of thoracic surgery in extracorporeal membrane oxygenation services
Authors: Heward Elliot , Hashmi Syed F , Malagon Ignacio , Shah Rajesh , Barker Julian , Rammohan Kandadai S 
Published: February 2018

Background Recent evidence surrounding the use of venovenous extracorporeal membrane oxygenation in treating acute respiratory failure has led to the expansion of extracorporeal membrane oxygenation services worldwide. The high rate of complications related to venovenous extracorporeal membrane oxygenation often requires intervention by specialist thoracic surgeons. This study aimed to investigate the role of specialist thoracic surgeons within the multidisciplinary team managing these high-risk patients. Methods We retrospectively reviewed 90 patients who received venovenous extracorporeal membrane oxygenation at our tertiary referral center between December 2011 and May 2015. Four patients who underwent lung transplantation were excluded. Results We found that 29.1% (25/86) of patients on venovenous extracorporeal membrane oxygenation had undergone a thoracic intervention. A total of 82 interventions were performed: 11 thoracotomies, 49 chest drains, 13 rigid bronchoscopies, 4 flexible bronchoscopies, 4 temporary endobronchial blockers, and 1 sternotomy. Of the 11 thoracotomies, 3 were reexplorations. Survival to discharge for patients who underwent thoracic surgical interventions was 72% (18/25). Conclusions Our experience has demonstrated that a large proportion of patients receiving venovenous extracorporeal membrane oxygenation require a thoracic intervention, many of which are major intraoperative procedures. Patients on venovenous extracorporeal membrane oxygenation have benefited from rapid on-site access to thoracic surgical services to manage these challenging life-threatening complications.
Persistent mania following cessation of corticosteroids
Authors: Roxanas Milton G 
Published: February 2018

Objectives: The aims of this study are to describe two patients whose manic symptoms persisted for several months after the cessation of corticosteroids, to review the literature and to suggest treatment. Methods: The presentation of two elderly patients with persistent manic symptoms following cessation of corticosteroids several months previously afforded the author the opportunity to examine them carefully, investigate and treat them. Results: The patients were investigated to rule out other causes and were treated with sodium valproate and quetiapine (in the second patient). When well, the medications were slowly decreased and stopped. Both patients were well at one-year follow-up. Conclusions: Manic symptoms may persist for many months after stopping corticosteroids and active treatment is needed to control them.
Dexmedetomidine Decreases Postoperative Pain and Narcotic Use in Children Undergoing Alveolar Bone Graft Surgery
Authors: Lopez Mariela M. , Zech Derrick , Linton Judith L. , Blackwell Steven J. 
Published: February 2018

Objective: Dexmedetomidine is a parenteral agent that combines the benefits of cooperative sedation, anxiolysis, and analgesia without the risks of respiratory depression. Off-label use has been reported in children. We have introduced dexmedetomidine for use in patients having undergone alveolar bone graft (ABG). The objective is to demonstrate the value and safety of postoperative dexmedetomidine infusion in a non-ICU setting following ABG. Design: A retrospective review was performed on patients who underwent ABG by the senior author. Patients were divided into 2 groups: those who received postoperative dexmedetomidine and those who received patient-controlled anesthesia. Main Outcome Measure(s): The primary study outcome measures included patient demographics, adverse events, length of stay, pain scores, and doses of narcotics during admission were collected. Results: Inclusion criteria were met by 54 patients; 39 received dexmedetomidine whereas 15 did not. There were no significant differences between groups in age, gender, and length of stay. The patients who received dexmedetomidine used oral narcotics less often ( P = .01). In addition, more patients reported no pain after surgery ( P = .05) and at the time of discharge if they received dexmedetomidine ( P < .01). There were no reported adverse effects. Conclusions: Dexmedetomidine provided superior pain control after surgery and at the time of discharge, as well as a significant decrease in the use of oral narcotics. In our institution, it has since replaced the PCA as a postoperative pain control modality. Absent the risk for respiratory depression, dexmedetomidine has demonstrated a safe option for postoperative pain control in our focused group of pediatric patients.
Employee Perceptions of the Work Environment, Motivational Outlooks, and Employee Work Intentions: An HR Practitioner’s Dream or Nightmare?
Authors: Shuck Brad , Peyton Roberts Taylor , Zigarmi Drea 
Published: February 2018

The Problem Reinforcement theory has inspired many types of human resource development (HRD) initiatives. Despite their widespread use, reinforcement-focused programs, designed to control the outcome of behavior through external rewards, have proven expensive and cumbersome to manage and have an alarmingly low rate of return on investment. There is a critical need to better understand motivation in work environments as well as to explore more efficacious forms of motivation, both intrinsic and extrinsic simultaneously. The Solution Self-determination theory (SDT) is concerned with forward influence, independent choice, and the degree to which behavior is internalized as self-determined. Sources of employee motivation are influenced by employee perceptions of the work environment as well as behavioral outcomes. The most optimal forms of motivation are believed to originate from internal regulation of basic psychological needs rather than external forms of motivation such as those central to reinforcement-focused theory and practice. The Stakeholders We question which forms of motivation are most optimal for influencing employee behavior in the workplace, including long-held traditions of reinforcement-grounded programming, and present new models for understanding the role of motivation in HRD. Results of this study focus the conversation on SDT and explore specific implications for practice.
Endovascular treatment of cerebral aneurysm after renal transplantation in polycystic kidney disease
Authors: Demartini Zeferino , Galdino Jennyfer , Koppe Gelson L , Bignelli Alexandre T , Francisco Alexandre N , Gatto Luana AM 
Published: February 2018

Background Patients with polycystic kidney disease have a higher prevalence of intracranial aneurysms and may progress to renal failure requiring transplantation. The endovascular treatment of intracranial aneurysms may improve prognosis, since rupture often causes premature death or disability, but the nephrotoxicity risk associated with contrast medium must be always considered in cases of renal impairment. Methods A 55-year-old female patient with polycystic kidney disease and grafted kidney associated with anterior communicant artery aneurysm was successfully treated by embolization. Results The renal function remained normal after the procedure. To the authors’ knowledge, this is the first case of endovascular treatment of brain aneurysm in a transplanted patient reported in the medical literature. Conclusions The endovascular procedure in renal transplant patients is feasible and can be considered to treat this population. Further studies and cases are needed to confirm its safety.
Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma
Authors: Spina Valeria , Bruscaggin Alessio , Cuccaro Annarosa , Martini Maurizio , Di Trani Martina , Forestieri Gabriela , Manzoni Martina , Condoluci Adalgisa , Arribas Alberto , Terzi-Di-Bergamo Lodovico , Locatelli Silvia Laura , Cupelli Elisa , Ceriani Luca , Moccia Alden A. , Stathis Anastasios , Nassi Luca , Deambrogi Clara , Diop Fary , Guidetti Francesca , Cocomazzi Alessandra , Annunziata Salvatore , Rufini Vittoria , Giordano Alessandro , Neri Antonino , Boldorini Renzo , Gerber Bernhard , Bertoni Francesco , Ghielmini Michele , Stüssi Georg , Santoro Armando , Cavalli Franco , Zucca Emanuele , Larocca Luigi Maria , Gaidano Gianluca , Hohaus Stefan , Carlo-Stella Carmelo , Rossi Davide 
Published: February 2018

Key Points
ctDNA is as an easily accessible source of tumor DNA for cHL genotyping. ctDNA is a radiation-free tool to track residual disease in cHL.
FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity
Authors: Ettinger Ruth A. , Liberman Joseph A. , Gunasekera Devi , Puranik Komal , James Eddie A. , Thompson Arthur R. , Pratt Kathleen P. 
Published: February 2018

Key PointsLess immunogenic FVIII muteins were designed by defining and replacing MHCII anchor residues with amino acids that reduced MHCII binding. Patient-derived T-cell clones show lower proliferation in response to FVIII-F2196K, which had normal FVIII activity and expression level.
Natural killer receptor ligand expression on acute myeloid leukemia impacts survival and relapse after chemotherapy
Authors: Mastaglio Sara , Wong Eric , Perera Travis , Ripley Jane , Blombery Piers , Smyth Mark J. , Koldej Rachel , Ritchie David 
Published: February 2018

Key Points
AML blasts express both activating and inhibitory NKRLs at diagnosis. An overall activating NK ligand phenotype on blasts is associated with improved survival and reduced relapse after induction chemotherapy.