bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter study evaluating the frequency and time requirement of mechanical thrombectomy
Authors: Wilson Taylor A , Leslie-Mazwi Thabele , Hirsch Joshua A , Frey Casey , Kim Teddy E , Spiotta Alejandro M , Leacy Reade de , Mocco J , Albuquerque Felipe C , Ducruet Andrew F , Cheema Ahmed , Arthur Adam , Srinivasan Visish M , Kan Peter , Mokin Maxim , Dumont Travis , Rai Ansaar , Singh Jasmeet , Wolfe Stacey Q , Fargen Kyle M 
Published: June 2017

IntroductionThere are few published data evaluating the incidence of mechanical thrombectomy among stroke centers or the times at which they occur.MethodsA multicenter retrospective study was performed to identify all patients undergoing emergent thrombectomy for acute ischemic stroke during a 3-month period (June through August 2016). Consultations that did not undergo thrombectomy were not included.ResultsTen institutions participated in the study. During the 92-day study period, a total of 189 patients underwent mechanical thrombectomy. The average number of procedures per hospital over the study period was 18.9 (average of 0.2 cases per day per or 75.6 cases per year). This ranged from 0.09 cases per day at the lowest volume center to 0.49 cases per day at the highest volume center. Procedures were more common on weekdays (p<0.001) and during non-work hours (p<0.001). The most common period for thrombectomy procedures was between 20:00 and 21:00 hours. The median time from notification to groin puncture was 84 min (IQR 56–145 min) and from puncture to closure was 57 min (IQR 33–80 min). The median time from imaging completion to procedural start was 52 min longer for non-work hours than during work hours (p<0.001). There were no differences in procedural length based on day of the week or time of day.ConclusionsThese findings indicate that the majority of mechanical thrombectomy cases occur during non-work hours, with associated off-hours delays, which has important operational implications for hospitals implementing stroke call coverage.
Blood pressure gradients in cerebral arteries: a clue to pathogenesis of cerebral small vessel disease
Authors: Blanco Pablo J , Müller Lucas O , Spence J David 
Published: June 2017

RationaleThe role of hypertension in cerebral small vessel disease is poorly understood. At the base of the brain (the ‘vascular centrencephalon’), short straight arteries transmit blood pressure directly to small resistance vessels; the cerebral convexity is supplied by long arteries with many branches, resulting in a drop in blood pressure. Hypertensive small vessel disease (lipohyalinosis) causes the classically described lacunar infarctions at the base of the brain; however, periventricular white matter intensities (WMIs) seen on MRI and WMI in subcortical areas over the convexity, which are often also called ‘lacunes’, probably have different aetiologies.ObjectivesWe studied pressure gradients from proximal to distal regions of the cerebral vasculature by mathematical modelling.Methods and resultsBlood flow/pressure equations were solved in an Anatomically Detailed Arterial Network (ADAN) model, considering a normotensive and a hypertensive case. Model parameters were suitably modified to account for structural changes in arterial vessels in the hypertensive scenario. Computations predict a marked drop in blood pressure from large and medium-sized cerebral vessels to cerebral peripheral beds. When blood pressure in the brachial artery is 192/113 mm Hg, the pressure in the small arterioles of the posterior parietal artery bed would be only 117/68 mm Hg. In the normotensive case, with blood pressure in the brachial artery of 117/75 mm Hg, the pressure in small parietal arterioles would be only 59/38 mm Hg.ConclusionThese findings have important implications for understanding small vessel disease. The marked pressure gradient across cerebral arteries should be taken into account when evaluating the pathogenesis of small WMIs on MRI. Hypertensive small vessel disease, affecting the arterioles at the base of the brain should be distinguished from small vessel disease in subcortical regions of the convexity and venous disease in the periventricular white matter.
Precision Medicine in Pediatric Oncology: Translating Genomic Discoveries into Optimized Therapies
Authors: Tran Thai Hoa , Shah Avanthi Tayi , Loh Mignon L. 
Published: June 2017

Abstract
Survival of children with cancers has dramatically improved over the past several decades. This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease, and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified “driver” genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents. Thus, the recently described genomic and epigenetic landscapes of many childhood cancers have expanded the paradigm of precision medicine in the hopes of improving outcomes while minimizing toxicities. In this review, we will discuss the biologic rationale for molecularly targeted therapies in genomically defined subsets of pediatric leukemias, solid tumors, and brain tumors. Clin Cancer Res; 23(18); 5329–38. ©2017 AACR.
Human Papillomavirus DNA Methylation Predicts Response to Treatment Using Cidofovir and Imiquimod in Vulval Intraepithelial Neoplasia 3
Authors: Jones Sadie E.F. , Hibbitts Samantha , Hurt Christopher N. , Bryant Dean , Fiander Alison N. , Powell Ned , Tristram Amanda J. 
Published: June 2017

AbstractPurpose: Response rates to treatment of vulval intraepithelial neoplasia (VIN) with imiquimod and cidofovir are approximately 57% and 61%, respectively. Treatment is associated with significant side effects and, if ineffective, risk of malignant progression. Treatment response is not predicted by clinical factors. Identification of a biomarker that could predict response is an attractive prospect. This work investigated HPV DNA methylation as a potential predictive biomarker in this setting.Experimental Design: DNA from 167 cases of VIN 3 from the RT3 VIN clinical trial was assessed. HPV-positive cases were identified using Greiner PapilloCheck and HPV 16 type-specific PCR. HPV DNA methylation status was assessed in three viral regions: E2, L1/L2, and the promoter, using pyrosequencing.Results: Methylation of the HPV E2 region was associated with response to treatment. For cidofovir (n = 30), median E2 methylation was significantly higher in patients who responded (P ≤ 0.0001); E2 methylation &gt;4% predicted response with 88.2% sensitivity and 84.6% specificity. For imiquimod (n = 33), median E2 methylation was lower in patients who responded to treatment (P = 0.03; not significant after Bonferroni correction); E2 methylation &lt;4% predicted response with 70.6% sensitivity and 62.5% specificity.Conclusions: These data indicate that cidofovir and imiquimod may be effective in two biologically defined groups. HPV E2 DNA methylation demonstrated potential as a predictive biomarker for the treatment of VIN with cidofovir and may warrant investigation in a biomarker-guided clinical trial. Clin Cancer Res; 23(18); 5460–8. ©2017 AACR.
Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity
Authors: Meulendijks Didier , Jacob Wolfgang , Voest Emile E. , Mau-Sorensen Morten , Martinez-Garcia Maria , Taus Alvaro , Fleitas Tania , Cervantes Andres , Lolkema Martijn P. , Langenberg Marlies H.G. , De Jonge Maja J. , Sleijfer Stefan , Han Ji-Youn , Calles Antonio , Felip Enriqueta , Kim Sang-We , Schellens Jan H.M. , Wilson Sabine , Thomas Marlene , Ceppi Maurizio , Meneses-Lorente Georgina , James Ian , Vega-Harring Suzana , Dua Rajiv , Nguyen Maitram , Steiner Lori , Adessi Celine , Michielin Francesca , Bossenmaier Birgit , Weisser Martin , Lassen Ulrik N. 
Published: June 2017

AbstractPurpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of HRG mRNA and HER3 mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib.Results: Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor HRG and HER3 mRNA levels were associated with a numerically higher disease control rate but not ORR.Conclusions: The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels. Clin Cancer Res; 23(18); 5406–15. ©2017 AACR.
Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk
Authors: Rees Judy R. , Morris Carolyn B. , Peacock Janet L. , Ueland Per M. , Barry Elizabeth L. , McKeown-Eyssen Gail E. , Figueiredo Jane C. , Snover Dale C. , Baron John A. 
Published: June 2017

AbstractIn a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence. We found no association between plasma mF or UFA and overall adenoma risk. However, during later follow-up, the prespecified, composite endpoint of high-risk findings (advanced or multiple adenomas) was positively associated with plasma mF (Plinear trend = 0.009), with a 58% increased risk for participants in the upper versus lowest quartile. An irregular association was seen with plasma UFA, with suggestions of an inverse trend (Plinear trend=0.049). A modest, significant inverse association was also seen between mF and risk of serrated lesions, with a 39% lower risk for upper versus lower quartile participants (Plinear trend = 0.03). In conclusion, during the later follow-up period in which folic acid supplementation was previously seen to increase the risk of advanced and multiple adenomas, higher serum mF was associated with a higher risk of multiple and/or advanced adenomas, but no clear indication that UFA played a direct role. There were indications that higher mF was associated with reduced risk of serrated polyps. Cancer Prev Res; 10(8); 451–8. ©2017 AACR.
Genetic Testing in the Evaluation of Unexplained Cardiac Arrest
Authors: Mellor Greg , Laksman Zachary W.M. , Tadros Rafik , Roberts Jason D. , Gerull Brenda , Simpson Christopher S. , Klein George J. , Champagne Jean , Talajic Mario , Gardner Martin , Steinberg Christian , Arbour Laura , Birnie David H. , Angaran Paul , Leather Richard , Sanatani Shubhayan , Chauhan Vijay S. , Seifer Colette , Healey Jeffrey S. , Krahn Andrew D. 
Published: June 2017

Background—
Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear.

Methods and Results—

The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians’ discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6–9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1–9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%;
P
=0.04) but was associated with more variants of unknown significance (55% versus 5%;
P
<0.01).

Conclusions—
Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients.

Clinical Trial Registration—

https://www.clinicaltrials.gov
. Unique Identifier: NCT00292032
Quantifying the Shift Toward Transcatheter Aortic Valve Replacement in Low-Risk Patients
Authors: De Sciscio Paolo , Brubert Jacob , De Sciscio Michele , Serrani Marta , Stasiak Joanna , Moggridge Geoff D. 
Published: June 2017

Background—
In recent years, use of transcatheter aortic valve replacement has expanded to include patients at intermediate- and low-risk cohorts. We sought to determine disease prevalence and treatment distribution including transcatheter aortic valve replacement eligibility in low-risk patients across 37 advanced economies.

Methods and Results—
Four systematic searches were conducted across MEDLINE, EMBASE, and the Cochrane database for studies evaluating disease prevalence, severity, decision making, and survival in patients with aortic stenosis. Estimates of disease prevalence and treatment eligibility were calculated using stochastic simulation and population data for the 37 countries comprising the International Monetary Fund’s advanced economies index. Fifty-six studies comprising 42 965 patients were included across 5 domains: prevalence, severity, symptom status, treatment modality, and outcome. The pooled prevalence in the general population aged 60 to 74 years and >75 years was 2.8% (95% confidence interval [CI], 1.4%–4.1%) and 13.1% (95% CI, 8.2%–17.9%), respectively—corresponding to an estimated 16.1 million (95% CI, 12.2–20.3) people in 37 advanced economies. Of these, an estimated 3.2 million (95% CI, 2.2–4.4) patients have severe aortic stenosis with 1.9 million (95% CI, 1.3–2.6) eligible for surgical aortic valve replacement. There are ≈485 230 (95% CI, 284 550–66 7350) high-risk/inoperable patients, 152 690 (95% CI, 73 410–263 000) intermediate-risk patients, and 378 890 (95% CI, 205 130–610 210) low-risk patients eligible for transcatheter aortic valve replacement.

Conclusions—
With a prevalence of 4.5%, an estimated 16.1 million people aged ≥60 years across 37 advanced economies have aortic stenosis. Of these, there are ≈1.9 million patients eligible for surgical aortic valve replacement and 1.0 million patients eligible for transcatheter aortic valve replacement.
Comparison of a Drug‐Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3‐Year Follow‐Up
Authors: Yahagi Kazuyuki , Yang Yi , Torii Sho , Mensah Johanne , White Roseann M. , Mathieu Marion , Pacheco Erica , Nakano Masataka , Barakat Abdul , Sharkawi Tahmer , Vert Michel , Joner Michael , Finn Aloke V. , Virmani Renu , Lafont Antoine 
Published: June 2017

Background

Arterial Remodeling Technologies bioresorbable scaffold (
ART
‐
BRS
), composed of
l
‐ and
d
‐lactyl units without drug, has shown its safety in a porcine coronary model at 6 months. However, long‐term performance remains unknown. The aim of this study was to evaluate the
ART
‐
BRS
compared to a bare metal stent (
BMS
) in a healthy porcine coronary model for up to 3 years.

Methods and Results

Eighty‐two
ART
‐
BRS
and 66
BMS
were implanted in 64 Yucatan swine, and animals were euthanatized at intervals of 1, 3, 6, 9, 12, 18, 24, and 36 months to determine the vascular response using quantitative coronary angiography, optical coherence tomography, light and scanning electron microscopy, and molecular weight analysis. Lumen enlargement was observed in
ART
‐
BRS
as early as 3 months, which progressively increased up to 18 months, whereas
BMS
showed no significant difference over time. Percentage area stenosis by optical coherence tomography was greater in
ART
‐
BRS
than in
BMS
at 1 and 3 months, but this relationship reversed beyond 3 months. Inflammation peaked at 6 months and thereafter continued to decrease up to 36 months. Complete re‐endothelialization was observed at 1 month following implantation in both
ART
‐
BRS
and
BMS
. Scaffold dismantling started at 3 months, which allowed early vessel enlargement, and bioresorption was complete by 24 months.

Conclusions

ART
‐
BRS
has the unique quality of early programmed dismantling accompanied by vessel lumen enlargement with mild to moderate inflammation. The main distinguishing feature of the
ART
‐
BRS
from other scaffolds made from poly‐
l
‐lactic acid may result in early and long‐term vascular restoration.
Jewish Philosophy, Science of Judaism and Philology in Salomon Munk and Samuel David Luzzatto’s Letters Exchange
Authors: Adorisio Chiara 
Published: June 2017

Abstract
The correspondence of the Italian Hebraist Samuel David Luzzatto (1800–1865) and the German-Jewish Orientalist Salomon Munk (1803–1867) sheds light on the trans-European dimension of the movement known as the Science of Judaism. This article is based on the reconstruction of the friendship between Luzzatto and Munk as reflected in Luzzatto’s letters to Munk in Paris. Their relationship was personal as well as intellectual: Luzzatto sent his son Philoxène, a promising Orientalist, to study under Munk’s supervision. Together with Munk’s letter to Philoxène, these letters provide us with details central to an understanding of the relationship between the two scholars. Although differing in their attitude toward Jewish faith and philosophy, Munk and Luzzatto shared a common interest in Hebrew and Oriental languages. Through their philological and linguistic studies, they challenged the Orientalistic attitude prevalent among European scholars and historians of philosophy in the first half of the nineteenth century.
Planning the Socialist Housing District in Bucharest and the Soviet influence, 1947–1960
Authors: Maxim Juliana 
Published: June 2017

This article details some of the processes through which Romanian architectural culture transformed under Soviet influence in the 1950s and through which architects came to redefine the organization of the profession, the planning of the city, and methods of design.
The urban housing district (referred to as cvartal) and the rationalization of architectural design through type-solutions (tipizare or typization) were two architectural themes of particular political consequence and thus especially subjected to the pressures of Soviet precedent. The article shows, however, that the Soviet principles and policies brought to bear on the design of architectural types and the planning of the cvartal belonged in large part to a set of generic modernist principles that crossed political lines.
The article aims to nuance the negative view of Sovietization as the imposition of entirely foreign concerns: archival sources, publications of the time, and architectural examples show that Soviet models reoriented but continued preexisting Romanian preoccupations with the planning of the modern city. Furthermore, Sovietization was not an isolationist phenomenon that hindered innovation: rather than standing as an obstacle to modernization, Soviet models connected Romania’s architectural culture to international postwar debates on mass housing and new urban forms.
Ernest Weissmann’s “World City”
Authors: Tolic Ines 
Published: June 2017

On July 26, 1963, the city of Skopje was struck by a powerful earthquake which left behind almost nothing but ruins. Financially precarious, technically unprepared and politically non-aligned, the Yugoslav government needed neutral, long-term and specialized technical assistance if the Macedonian capital was to be rebuilt. Thanks to mediation of Ernest Weissmann, an architect of Croatian origins and a un officer at ecosoc, the United Nations joined in the reconstruction on October 14, 1963, and, in the following years, some of the most renowned contemporary architects and urban planners were invited to present their vision for the New Skopje. According to Weissmann, the city was to became nothing less than a “world city,” providing solutions to the contemporary “urban crisis,” prescribing a cure for “sick cities,” and showing the way for the “humanization” of the built environment. Even though mostly unattained, these ambitious goals gave birth to an international debate about the future of both cities and city planning, which was decisive for the definition of the un’s later interventions. The goal of this paper is to deal with Skopje’s reconstruction, highlighting Ernest Weissmann’s role in it, and to describe the city as a node of knowledge within a network of specialists in urban matters established by the United Nations during and – most of all – in spite of the Cold War context.