bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the effectiveness and safety of the carotid Casper-RX stent for tandem lesions in acute ischemic stroke
Authors: Bartolini Bruno , Puccinelli Francesco , Mosimann Pascal J , Hajdu Steven D , Veunac Louis , Michel Patrik , Saliou Guillaume 
Published: December 2018

IntroductionA new generation of carotid artery stents that use a dual micromesh layer to reduce embolic events during carotid artery stenting has recently been introduced. We aimed to analyze the effectiveness and safety of the new Casper-RX stent in patients experiencing acute ischemic stroke with large vessel intracranial occlusion associated with a tandem lesion (another carotid occlusion or severe stenosis).MethodsWe retrospectively analyzed all consecutive patients treated with carotid Casper-RX stents from our stroke registry. We analyzed clinical, angiographic, and neuroimaging data. Endpoints included acute intra-stent thrombus formation, stent occlusion prior to hospital discharge, 3 month modified Rankin Scale score (mRS), and symptomatic intracranial hemorrhage.Results21 patients were included: 10 patients had tandem carotid occlusions and 11 patients had severe carotid stenosis, 8 of whom had a hemodynamically significant stenosis. We observed acute in-stent thrombus formation in 11 patients. No stent occlusion occurred prior to hospital discharge. We report no stroke recurrence at 3 months but symptomatic intracranial hemorrhage in two patients. mRS score at 3 months was 0–2 (favorable) for 15 patients (71%), 3–5 for 3 patients, and 6 for 3 patients.ConclusionsIn the present series, we frequently observed clot formation during the procedure with Casper-RX stents, which required periprocedural intravenous infusion of anticoagulant and antiplatelet treatment. This motivated us, in the absence of a prospective randomized controlled study demonstrating the non-inferiority of micromesh dual layer stents compared with the single layer design, to discontinue using this stent type in acute stroke requiring carotid angioplasty.
Effects of flavonoids from Allium mongolicum Regel as a dietary additive on meat quality and composition of fatty acids related to flavor in lambs
Authors: Liu Wangjing , Ding He , Erdene Khas , Chen Renwei , Mu Qier , Ao Changjin 
Published: December 2018

Sixty male Small-tailed Han sheep (initial body weight: 42.5 ± 4.1 kg) were assigned randomly and averagely into four groups to evaluate effects of flavonoids extracted from Allium mongolicum Regel (AMR) on meat quality and composition of fatty acids related to flavor in longissimus dorsi muscle of lambs. Lambs of four groups were fed a basal control diet (C), and basal diet + three different amounts of flavonoids extracted from the AMR; those were 11 mg kg−1 (Flav 11), 22 mg kg−1 (Flav 22), or 33 mg kg−1 (Flav 33), respectively. Dressing percentage, loin eye area, cooking loss, and pressing loss were affected by treatments (P < 0.05). Percentage of intramuscular fat, the concentrations of eicosapentaenoic acid, C18:0, total saturated fatty acids, monounsaturated fatty acid, and 4-methyloctanoic acid in longissimus dorsi muscle were changed by treatments (P < 0.05). Addition of AMR to diet improved the meat quality and had favorable effects on fatty acid composition related to meat flavor in longissimus dorsi muscle.
Putting in all the stops: execution control for JavaScript
Authors: Baxter Samuel , Nigam Rachit , Politz Joe Gibbs , Krishnamurthi Shriram , Guha Arjun 
Published: December 2018

Scores of compilers produce JavaScript, enabling programmers to use many languages on the Web, reuse existing code, and even use Web IDEs. Unfortunately, most compilers inherit the browser's compromised execution model, so long-running programs freeze the browser tab, infinite loops crash IDEs, and so on. The few compilers that avoid these problems suffer poor performance and are difficult to engineer.
This paper presents Stopify, a source-to-source compiler that extends JavaScript with debugging abstractions and blocking operations, and easily integrates with existing compilers. We apply Stopify to ten programming languages and develop a Web IDE that supports stopping, single-stepping, breakpointing, and long-running computations. For nine languages, Stopify requires no or trivial compiler changes. For eight, our IDE is the first that provides these features. Two of our subject languages have compilers with similar features. Stopify's performance is competitive with these compilers and it makes them dramatically simpler.
Stopify's abstractions rely on first-class continuations, which it provides by compiling JavaScript to JavaScript. We also identify sub-languages of JavaScript that compilers implicitly use, and exploit these to improve performance. Finally, Stopify needs to repeatedly interrupt and resume program execution. We use a sampling-based technique to estimate program speed that outperforms other systems.
Certified concurrent abstraction layers
Authors: Gu Ronghui , Shao Zhong , Kim Jieung , Wu Xiongnan (Newman) , Koenig Jérémie , Sjöberg Vilhelm , Chen Hao , Costanzo David , Ramananandro Tahina 
Published: December 2018

Concurrent abstraction layers are ubiquitous in modern computer systems because of the pervasiveness of multithreaded programming and multicore hardware. Abstraction layers are used to hide the implementation details (e.g., fine-grained synchronization) and reduce the complex dependencies among components at different levels of abstraction. Despite their obvious importance, concurrent abstraction layers have not been treated formally. This severely limits the applicability of layer-based techniques and makes it difficult to scale verification across multiple concurrent layers.
In this paper, we present CCAL---a fully mechanized programming toolkit developed under the CertiKOS project---for specifying, composing, compiling, and linking certified concurrent abstraction layers. CCAL consists of three technical novelties: a new game-theoretical, strategy-based compositional semantic model for concurrency (and its associated program verifiers), a set of formal linking theorems for composing multithreaded and multicore concurrent layers, and a new CompCertX compiler that supports certified thread-safe compilation and linking. The CCAL toolkit is implemented in Coq and supports layered concurrent programming in both C and assembly. It has been successfully applied to build a fully certified concurrent OS kernel with fine-grained locking.
Finding root causes of floating point error
Authors: Sanchez-Stern Alex , Panchekha Pavel , Lerner Sorin , Tatlock Zachary 
Published: December 2018

Floating-point arithmetic plays a central role in science, engineering, and finance by enabling developers to approximate real arithmetic. To address numerical issues in large floating-point applications, developers must identify root causes, which is difficult because floating-point errors are generally non-local, non-compositional, and non-uniform.
This paper presents Herbgrind, a tool to help developers identify and address root causes in numerical code written in low-level languages like C/C++ and Fortran. Herbgrind dynamically tracks dependencies between operations and program outputs to avoid false positives and abstracts erroneous computations to simplified program fragments whose improvement can reduce output error. We perform several case studies applying Herbgrind to large, expert-crafted numerical programs and show that it scales to applications spanning hundreds of thousands of lines, correctly handling the low-level details of modern floating point hardware and mathematical libraries and tracking error across function boundaries and through the heap.
Static serializability analysis for causal consistency
Authors: Brutschy Lucas , Dimitrov Dimitar , Müller Peter , Vechev Martin 
Published: December 2018

Many distributed databases provide only weak consistency guarantees to reduce synchronization overhead and remain available under network partitions. However, this leads to behaviors not possible under stronger guarantees. Such behaviors can easily defy programmer intuition and lead to errors that are notoriously hard to detect.
In this paper, we propose a static analysis for detecting non-serializable behaviors of applications running on top of causally-consistent databases. Our technique is based on a novel, local serializability criterion and combines a generalization of graph-based techniques from the database literature with another, complementary analysis technique that encodes our serializability criterion into first-order logic formulas to be checked by an SMT solver. This analysis is more expensive yet more precise and produces concrete counter-examples.
We implemented our methods and evaluated them on a number of applications from two different domains: cloud-backed mobile applications and clients of a distributed database. Our experiments demonstrate that our analysis is able to detect harmful serializability violations while producing only a small number of false alarms.
A National Bowel Cancer Screening Programme using FIT: Achievements and Challenges
Authors: O'Donoghue Diarmuid , Sheahan Kieran , MacMathuna Padraic , Stephens Richard B. , Fenlon Helen , Morrin Martina , Mooney Jenny , Fahy Lorraine E. , Mooney Therese , Smith Alan 
Published: December 2018

Abstract
Colorectal cancer accounts for 11% of all cancer-related deaths in Ireland. With the aim of diagnosing these cancers at an earlier stage, and detecting premalignant lesions, the National Screening Service (NSS) offered a fecal immunochemical test (FIT) to all individuals aged 60 to 69. All individuals in the age range were contacted by post and invited to participate in the programme. Those with a positive FIT result were offered a colonoscopy in an internationally accredited unit. From an eligible population of 488,628, 196,238 individuals participated giving an uptake of 40.2%. Commencing at a FIT threshold of 20 μg Hg/g feces, the positivity rate was 8.6%, which overwhelmed colonoscopy capacity and, thus, the threshold was increased to 45 μg, resulting in an overall 5% positivity rate. A total of 520 individuals had cancer detected (68.3% stage I or II), of which 104 were removed endoscopically (pT1s). Adenomas were present in 54.2% of all colonoscopies, 17.4% deemed high risk. Despite a lower uptake, males were twice as likely to have colorectal cancers as females and had a 59% increased rate of high-risk adenomas diagnosed. Challenges facing the programme include increasing participation, especially among males, and increasing colonoscopy capacity. The ability to alter the sensitivity of FIT to match colonoscopy capacity is a valuable option for such a programme as it ensures that the maximum public health benefit can be achieved within available resources.
Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia
Authors: Blombery Piers , Anderson Mary Ann , Gong Jia-nan , Thijssen Rachel , Birkinshaw Richard W. , Thompson Ella R. , Teh Charis E. , Nguyen Tamia , Xu Zhen , Flensburg Christoffer , Lew Thomas E. , Majewski Ian J. , Gray Daniel H.D. , Westerman David A. , Tam Constantine S. , Seymour John F. , Czabotar Peter E. , Huang David C.S. , Roberts Andrew W. 
Published: December 2018

Abstract

The BCL2 inhibitor venetoclax induces high rates of durable remission in patients with previously treated chronic lymphocytic leukemia (CLL). However, despite continuous daily treatment, leukemia recurs in most patients. To investigate the mechanisms of secondary resistance, we analyzed paired pre-venetoclax and progression samples from 15 patients with CLL progression enrolled on venetoclax clinical trials. The novel Gly101Val mutation in BCL2 was identified at progression in 7 patients, but not at study entry. It was first detectable after 19 to 42 months of therapy, and its emergence anticipated clinical disease progression by many months. Gly101Val reduces the affinity of BCL2 for venetoclax by ∼180-fold in surface plasmon resonance assays, thereby preventing the drug from displacing proapoptotic mediators from BCL2 in cells and conferring acquired resistance in cell lines and primary patient cells. This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse.

Significance:
Why CLL recurs in patients who achieve remission with the BCL2 inhibitor venetoclax has been unknown. We provide the first description of an acquired point mutation in BCL2 arising recurrently and exclusively in venetoclax-treated patients. The mutation reduces venetoclax binding and is sufficient to confer resistance.
See related commentary by Thangavadivel and Byrd, p. 320.
This article is highlighted in the In This Issue feature, p. 305
CD16+NKG2Ahigh Natural Killer Cells Infiltrate Breast Cancer–Draining Lymph Nodes
Authors: Frazao Alexandra , Messaoudene Meriem , Nunez Nicolas , Dulphy Nicolas , Roussin France , Sedlik Christine , Zitvogel Laurence , Piaggio Eliane , Toubert Antoine , Caignard Anne 
Published: December 2018

Abstract
Tumor-draining lymph nodes (TD-LNs) are the first site of metastasis of breast cancer. Natural killer (NK) cells that infiltrate TD-LNs [including noninvaded (NI) or metastatic (M)-LNs from breast cancer patients] and NK cells from healthy donor (HD)-LNs were characterized, and their phenotype analyzed by flow cytometry. Low percentages of tumor cells invaded M-LNs, and these cells expressed ULBP2 and HLA class I molecules. Although NK cells from paired NI and M-LNs were similar, they expressed different markers compared with HD-LN NK cells. Compared with HD-LNs, TD-LN NK cells expressed activating DNAM-1, NKG2C and inhibitory NKG2A receptors, and exhibited elevated CXCR3 expression. CD16, NKG2A, and NKp46 expression were shown to be increased in stage IIIA breast cancer patients. TD-LNs contained a large proportion of activated CD56brightCD16+ NK cells with high expression of NKG2A. We also showed that a subset of LN NK cells expressed PD-1, expression of which was correlated with NKp30 and NKG2C expression. LN NK cell activation status was evaluated by degranulation potential and lytic capacity toward breast cancer cells. NK cells from TD-LNs degranulated after coculture with breast cancer cell lines. Cytokine-activated TD-LN NK cells exerted greater lysis of breast cancer cell lines than HD-LN NK cells and preferentially lysed the HLA class Ilow MCF-7 breast cancer cell line. TD-LNs from breast cancer patients, thus, contained activated lytic NK cells. The expression of inhibitory receptor NKG2A and checkpoint PD-1 by NK cells infiltrating breast cancer–draining LNs supports their potential as targets for immunotherapies using anti-NKG2A and/or anti–PD-1.
Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function
Authors: Clavijo Paul E. , Friedman Jay , Robbins Yvette , Moore Ellen C. , Smith Ernest , Zauderer Maurice , Evans Elizabeth E. , Allen Clint T. 
Published: December 2018

Abstract
Tumor infiltration by immunosuppressive myeloid cells, such as myeloid-derived suppressor cells (MDSCs), causes resistance to immunotherapy. Semaphorin4D, originally characterized for its axonal guidance properties, also contributes to endothelial cell migration and survival and modulates global immune cytokine profiles and myeloid cell polarization within the tumor microenvironment. Here, we show how a therapeutic murine Sema4D mAb improves responses to immune-checkpoint blockade (ICB) in two murine carcinoma models. Treatment of tumor-bearing mice with Sema4D mAb abrogated Ly6Ghi PMN-MDSC recruitment through reducing MAPK-dependent chemokine production by tumor cells in Murine oral cancer-1 (MOC1) tumors. PMN-MDSC suppressive capacity was reduced through inhibition of Sema4D-driven arginase expression. These changes led to enhanced tumor infiltration by CD8+ TIL and activation of tumor-draining lymph node T lymphocytes in response to tumor antigen. Sema4D mAb in combination with either CTLA-4 or PD-1 blockade enhanced rejection of tumors or tumor growth delay, resulting in prolonged survival with either treatment. This function of Sema4D mAb provides a rationale for its evaluation in combination with ICB to treat tumors with immunosuppressive myeloid infiltration.
Impact of Frailty on Mortality and Hospitalization in Chronic Heart Failure: A Systematic Review and Meta‐Analysis
Authors: Yang Xiaobo , Lupón Josep , Vidán Maria T. , Ferguson Caleb , Gastelurrutia Paloma , Newton Phillip J. , Macdonald Peter S. , Bueno Héctor , Bayés‐Genís Antoni , Woo Jean , Fung Erik 
Published: December 2018

Background
Although frailty has been associated with increased risks for hospitalization and mortality in chronic heart failure, the precise average effect remains uncertain. We performed a systematic review and meta‐analysis to summarize the hazards for mortality and incident hospitalization in patients with heart failure and frailty compared with those without frailty and explored the heterogeneity underlying the effect size estimates.

Methods and Results

MEDLINE
,
EMBASE,
and Cochrane databases were queried for articles published between January 1966 and March 2018. Predefined selection criteria were used. Hazard ratios (
HRs
) were pooled for meta‐analyses, and where odds ratios were used previously, original data were recalculated for
HR
. Overlapping data were consolidated, and only unique data points were used. Study quality and bias were assessed. Eight studies were included for mortality (2645 patients), and 6 studies were included for incident hospitalization (2541 patients) during a median follow‐up of 1.82 and 1.12 years, respectively. Frailty was significantly associated with an increased hazard for mortality (
HR
, 1.54; 95% confidence interval, 1.34–1.75;
P
<0.001) and incident hospitalization (
HR
, 1.56; 95% confidence interval, 1.36–1.78;
P
<0.001) in chronic heart failure. The Fried phenotype estimated a 16.9% larger effect size than the combined Fried/non‐Fried frailty assessment for the end point of mortality (
HR
, 1.80; 95% confidence interval, 1.41–2.28;
P
<0.001), but not for hospitalization (
HR
, 1.57; 95% confidence interval, 1.30–1.89;
P
<0.001). Study heterogeneity was found to be low (I
2
=0%), and high quality of studies was verified by the Newcastle‐Ottawa scale.

Conclusions
Overall, the presence of frailty in chronic heart failure is associated with an increased hazard for death and hospitalization by ≈1.5‐fold.
Young Women With Coronary Artery Disease Exhibit Higher Concentrations of Interleukin‐6 at Baseline and in Response to Mental Stress
Authors: Sullivan Samaah , Hammadah Muhammad , Wilmot Kobina , Ramadan Ronnie , Pearce Brad D. , Shah Amit , Kaseer Belal , Gafeer Mohamad Mazen , Lima Bruno B. , Kim Jeong Hwan , Ward Laura , Ko Yi‐An , Lewis Tené T. , Hankus Allison , Elon Lisa , Li Lian , Bremner J. Douglas , Raggi Paolo , Quyyumi Arshed , Vaccarino Viola 
Published: December 2018

Background

Young women with coronary artery disease (
CAD
), a group with high psychosocial burden, were previously shown to have higher levels of interleukin‐6 (
IL
‐6) compared with men of similar age. We sought to examine
IL
‐6 response to acute stress in
CAD
patients across sex and age, and contrast results to healthy controls and other biomarkers known to increase with mental stress (monocyte chemoattractant protein‐1 and matrix metallopeptidase‐9) and known limited stress‐reactivity (high‐sensitivity C‐reactive protein).

Methods and Results

Inflammatory biomarkers were measured at rest and 90 minutes after mental stress (speech task) among 819 patients with
CAD
and 89 healthy controls. Repeated‐measures models were used to investigate age (continuous) and sex differences across time, before and after adjusting for demographics,
CAD
risk factors, depressive symptoms, medication use, and
CAD
severity. Among patients with
CAD
, the mean age was 60 years (range, 25–79) and 31% were women. Younger women with
CAD
had significantly higher concentrations of
IL
‐6 at rest, 90 minutes after mental stress, as well as a higher response to stress, compared with similarly aged men (
P
<0.05 for sex by age interactions). In contrast,
IL
‐6 increased with age, and there were no sex differences in
IL
‐6 levels or response to stress among controls. Inflammatory responses to stress for high‐sensitivity C‐reactive protein, monocyte chemoattractant protein‐1, and matrix metallopeptidase‐9 among
CAD
patients were similar in women and men.

Conclusions

IL
‐6 response to mental stress are higher in young women with
CAD
than men of similar age.
Tadpole of the hylid frog Bokermannohyla gouveai (Peixoto &amp; Cruz, 1992)
Authors: COSTA PAULO NOGUEIRA , LOURENÇO ANA CAROLINA CALIJORNE , ALMEIDA-SANTOS PATRICIA , VAN SLUYS MONIQUE 
Published: December 2018

The genus Bokermannohyla Faivovich, Haddad, Garcia, Frost, Campbell & Wheeler, 2005 currently comprises 29 species that are distributed in the Atlantic Forest and Cerrado biomes of Brazil (Faivovich et al. 2009; Frost 2010; Napoli & Pimenta 2009). This genus has recently been erected to accommodate the former Hyla circumdata, Hyla claresignata, Hyla martinsi, and Hyla pseudopseudis species groups (Faivovich et al. 2005). The Bokermannohyla circumdata group is composed by seventeen species (Table 1), all occurring mainly in mountain stream habitats in the Atlantic Rainforest, being the dark vertical stripes on the posterior surface of the thigh a putative morphological synapomorphy of this group (Heyer 1985). Despite the importance of larval characters for phylogenetic and taxonomic studies (e.g. Haas 2003), tadpoles of only seven species are formally described for this group (Table 1). Herein we describe the tadpole of B. gouveai known only from habitats above 1800 m (IUCN, 2010) in the Parque Nacional do Itatiaia, States of Rio de Janeiro and Minas Gerais, southeastern Brazil.
Comparisons of Electromagnetic Scattering Properties of Real Hailstones and Spheroids
Authors: Jiang Zhiyuan , Kumjian Matthew R. , Schrom Robert S. , Giammanco Ian , Brown-Giammanco Tanya , Estes Heather , Maiden Ross , Heymsfield Andrew J. 
Published: December 2018

AbstractSevere (>2.5 cm) hail causes >$5 billion in damage annually in the United States. However, radar sizing of hail remains challenging. Typically, spheroids are used to represent hailstones in radar forward operators and to inform radar hail-sizing algorithms. However, natural hailstones can have irregular shapes and lobes; these details significantly influence the hailstone’s scattering properties. The high-resolution 3D structure of real hailstones was obtained using a laser scanner for hail collected during the 2016–17 Insurance Institute for Business and Home Safety (IBHS) Hail Field Study. Plaster casts of several record hailstones (e.g., Vivian, South Dakota, 2010) were also scanned. The S-band scattering properties of these hailstones were calculated with the discrete dipole approximation (DDA). For comparison, scattering properties of spheroidal approximations of each hailstone (with identical maximum and minimum dimensions and mass) were calculated with the T matrix. The polarimetric radar variables have errors when using spheroids, even for small hail. Spheroids generally have smaller variations in the polarimetric variables than the real hailstones. This increased variability is one reason why the correlation coefficienttends to be lower in observations than in forward-simulated cases using spheroids. Backscatter differential phaseδalso is found to have large variance, particularly for large hailstones. Irregular hailstones with a thin liquid layer produce enhanced and more variable values for reflectivity factor at horizontal polarizationZHH, differential reflectivityZDR, specific differential phaseKDP, linear depolarization ratio (LDR), andδcompared with dry hailstones;is also significantly reduced.