bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism: protocol for a systematic review and meta-analysis of individual participant data
Authors: Robin Philippe , Eddy Maggie , Sikora Lindsey , Le Roux Pierre-Yves , Carrier Marc , Couturaud Francis , Planquette Benjamin , Pesavento Raffaele , Rodger Marc , Salaun Pierre-Yves , Le Gal Grégoire 
Published: November 2018

BackgroundIn patients with a first, unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulant therapy (AT) is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. The objective of this study is to assess among patients with a first acute pulmonary embolism (PE) who received ≥3 months of AT and thereafter had a planar lung scan, whether residual pulmonary vascular obstruction (RPVO) is associated with VTE recurrence after discontinuation of AT.Methods and analysisWe will conduct a systematic review with a meta-analysis of individual participant data of contemporary studies evaluating the prognostic significance of RPVO in patients with a first acute PE. We will search from inception to 24 January 2018, PubMed, Medline, Embase and Cochrane’s Central Registry for Randomized Controlled Trials, CENTRAL for randomized controlled trials and prospective cohort studies. Two reviewers will conduct all screening and data collection independently. The methodological quality and risk of bias of eligible studies will be carefully and rigorously assessed using the Risk Of Bias In Non-randomised Studies of Interventions tool. The primary objective will be to assess the relationship between RPVO on ventilation–perfusion scan after completion of at least 3 months of AT after an acute PE event, and the risk of an objectively confirmed symptomatic recurrent VTE (including deep vein thrombosis or PE) or death due to PE. The secondary objectives will include the assessment of the optimal RPVO cut-off and the risk of recurrent VTE, as well as the relationship between the relative change in RPVO between PE diagnosis and at discontinuation of AT (≥3 months) and risk of recurrent VTE.Ethics and disseminationThis study of secondary data does not require ethics approval. It will be presented internationally and published in the peer-reviewed literature.PROSPERO registration numberCRD42017081080.
Efficient Memristor-Based Architecture for Intrusion Detection and High-Speed Packet Classification
Authors: Bontupalli Venkataramesh , Yakopcic Chris , Hasan Raqibul , Taha Tarek M. 
Published: November 2018

Deep packet inspection (DPI) is a critical component to prevent intrusion detection. This requires a detailed analysis of each network packet header and body. Although this is often done on dedicated high-power servers in most networked systems, mobile systems could potentially be vulnerable to attack if utilized on an unprotected network. In this case, having DPI hardware on the mobile system would be highly beneficial. Unfortunately, DPI hardware is generally area and power consuming, making its implementation difficult in mobile systems.
We developed a memristor crossbar-based approach, inspired by memristor crossbar neuromorphic circuits, for a low-power, low-area, and high-throughput DPI system that examines both the header and body of a packet. Two key types of circuits are presented: static pattern matching and regular expression circuits. This system is able to reduce execution time and power consumption due to its high-density grid and massive parallelism. Independent searches are performed using low-power memristor crossbar arrays giving rise to a throughput of 160Gbps with no loss in the classification accuracy.
Hypoxia-induced vagal withdrawal is independent of the hypoxic ventilatory response in men
Authors: Siebenmann Christoph , Ryrsø Camilla K. , Oberholzer Laura , Fisher James P. , Hilsted Linda M. , Rasmussen Peter , Secher Niels H. , Lundby Carsten 
Published: November 2018

Hypoxia increases heart rate (HR) in humans by sympathetic activation and vagal withdrawal. However, in anaesthetized dogs hypoxia increases vagal activity and reduces HR if pulmonary ventilation does not increase and we evaluated whether that observation applies to awake humans. Ten healthy males were exposed to 15 min of normoxia and hypoxia (10.5% O2), while respiratory rate and tidal volume were volitionally controlled at values identified during spontaneous breathing in hypoxia. End-tidal CO2 tension was clamped at 40 mmHg by CO2 supplementation. β-Adrenergic blockade by intravenous propranolol isolated vagal regulation of HR. During spontaneous breathing, hypoxia increased ventilation by 3.2 ± 2.1 l/min ( P = 0.0033) and HR by 8.9 ± 5.5 beats/min ( P < 0.001). During controlled breathing, respiratory rate (16.3 ± 3.2 vs. 16.4 ± 3.3 breaths/min) and tidal volume (1.05 ± 0.27 vs. 1.06 ± 0.24 l) were similar for normoxia and hypoxia, whereas the HR increase in hypoxia persisted without (8.6 ± 10.2 beats/min) and with (6.6 ± 5.6 beats/min) propranolol. Neither controlled breathing ( P = 0.80), propranolol ( P = 0.64), nor their combination ( P = 0.89) affected the HR increase in hypoxia. Arterial pressure was unaffected ( P = 0.48) by hypoxia across conditions. The hypoxia-induced increase in HR during controlled breathing and β-adrenergic blockade indicates that hypoxia reduces vagal activity in humans even when ventilation does not increase. Vagal withdrawal in hypoxia seems to be governed by the arterial chemoreflex rather than a pulmonary inflation reflex in humans. NEW & NOTEWORTHY Hypoxia accelerates the heart rate of humans by increasing sympathetic activity and reducing vagal activity. Animal studies have indicated that hypoxia-induced vagal withdrawal is governed by a pulmonary inflation reflex that is activated by the increased pulmonary ventilation in hypoxia. The present findings, however, indicate that humans experience vagal withdrawal in hypoxia even if ventilation does not increase, indicating that vagal withdrawal is governed by the arterial chemoreflex rather than a pulmonary inflation reflex.
Antagonism of Glycolysis and Reductive Carboxylation of Glutamine Potentiates Activity of Oncolytic Adenoviruses in Cancer Cells
Authors: Dyer Arthur , Schoeps Benjamin , Frost Sally , Jakeman Philip , Scott Eleanor M. , Freedman Joshua , Jacobus Egon J. , Seymour Leonard W. 
Published: November 2018

Abstract

Tumor cells exhibiting the Warburg effect rely on aerobic glycolysis for ATP production and have a notable addiction to anaplerotic use of glutamine for macromolecular synthesis. This strategy maximizes cellular biosynthetic potential while avoiding excessive depletion of NAD+ and provides an attractive anabolic environment for viral infection. Here, we evaluate infection of highly permissive and poorly permissive cancer cells with wild-type adenoviruses and the oncolytic chimeric adenovirus enadenotucirev (EnAd). All adenoviruses caused an increase in glucose and glutamine uptake along with increased lactic acid secretion. Counterintuitively, restricting glycolysis using 2-deoxyglucose or by limiting glucose supply strongly improved virus activity in both cell types. Antagonism of glycolysis also boosted EnAd replication and transgene expression within human tumor biopsies and in xenografted tumors in vivo. In contrast, the virus life cycle was critically dependent on exogenous glutamine. Virus activity in glutamine-free cells was rescued with exogenous membrane-permeable α-ketoglutarate, but not pyruvate or oxaloacetate, suggesting an important role for reductive carboxylation in glutamine usage, perhaps for production of biosynthetic intermediates. This overlap between the metabolic phenotypes of adenovirus infection and transformed tumor cells may provide insight into how oncolytic adenoviruses exploit metabolic transformation to augment their selectivity for cancer cells.

Significance:
This study describes changes in glucose and glutamine metabolism induced by oncolytic and wild-type adenoviruses in cancer cells, which will be important to consider in the preclinical evaluation of oncolytic viruses.
Replication Stress: An Achilles' Heel of Glioma Cancer Stem–like Cells
Authors: Morgan Meredith A. , Canman Christine E. 
Published: November 2018

Abstract
Glioblastoma (GBM) is a highly aggressive form of cancer that is resistant to standard therapy with concurrent radiation and temozolomide, two agents that work by inducing DNA damage. An underlying cause of this resistance may be a subpopulation of cancer stem–like cells that display a heightened DNA damage response (DDR). Although this DDR represents an attractive therapeutic target for overcoming the resistance of GBMs to radiotherapy, until now, the cause of this DDR upregulation has not been understood. In a previous issue of Cancer Research, Carruthers and colleagues investigated DNA replication stress as an underlying mechanism responsible for upregulation of the DDR and hence the radiation resistance of glioma stem–like cells. Furthermore, the authors explore the efficacy of combined ataxia telangiectasia and Rad3-related kinase and PARP inhibitors as a strategy to leverage these mechanisms and overcome radiation resistance.
See related article by Carruthers and colleagues, Cancer Res; 78(17); 5060–71.
Development of PARP and Immune-Checkpoint Inhibitor Combinations
Authors: Stewart Ross A , Pilié Patrick G , Yap Timothy A 
Published: November 2018

AbstractPARP inhibitors drive increased DNA damage, particularly in tumors with existing defects in DNA repair. This damage not only promotes immune priming through a range of molecular mechanisms, but also leads to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. In this context, PARP inhibition and programmed cell death 1(PD-1)/PD-L1–targeting antibodies represent a rationale combination. In this review, we detail the basic and translational science underpinning this promising new combination, summarize available clinical data, and discuss the key questions that remain to be addressed during future development.
Clinical Development of Novel Drug–Radiotherapy Combinations
Authors: Ahmad Saif S. , Crittenden Marka R. , Tran Phuoc T. , Kluetz Paul G. , Blumenthal Gideon M. , Bulbeck Helen , Baird Richard D. , Williams Kaye J. , Illidge Tim , Hahn Stephen M. , Lawrence Theodore S. , Spears Patricia A. , Walker Amanda J. , Sharma Ricky A. 
Published: November 2018

Abstract
Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized. In view of this lack of progress, the FDA–AACR–ASTRO Clinical Development of Drug–Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups, and the FDA to discuss challenges to introducing new drug–radiotherapy combinations to the clinic. This Perspectives in Regulatory Science and Policy article summarizes the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies that efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation, and patient-reported outcomes. Novel approaches including immune-oncology or DNA-repair inhibitor agents combined with radiotherapy should be prioritized. In this article, we focus on how the regulatory challenges associated with defining a new drug–radiotherapy combination can be overcome to improve clinical outcomes for patients with cancer.
A non-invasive water-borne hormone assay for amphibians
Authors: Gabor Caitlin R. , Gabor Caitlin R. , Bosch Jaime , Gabor Caitlin R. , Bosch Jaime , Fries Joe N. , Gabor Caitlin R. , Bosch Jaime , Fries Joe N. , Davis Drew R. 
Published: November 2018

Anthropogenic disturbances have been implicated in the rapid decline of amphibians. Disturbances, such as disease and poor water quality, might cause changes in the physiology of amphibians resulting in chronic stress, which can result in decreased growth and development as well as immunosuppression. In amphibians, corticosterone (CORT) is the main hormone released in response to stressors. We took the first steps towards validating a new, non-invasive, technique to assay CORT in amphibians using a water-borne collection method previously used only with fish. In validation of this technique, we found a significant positive correlation between release rates of water-borne CORT and levels of CORT in circulating plasma in adults of the San Marcos salamander, Eurycea nana, and the common midwife toad, Alytes obstetricans. These results indicate that water-borne CORT can be used as a proxy for plasma CORT. Additionally, we examined basic background information on the physiological states of these two species. We found that captive-reared salamanders had significantly lower release rates of CORT than field-collected salamanders. Field-collected salamanders had significantly higher CORT release rates 24 h after capture and transfer to the laboratory. For tadpoles, we found that field-collected tadpoles did not have significantly different CORT release rates than those maintained in the laboratory for four months. Our research indicates that this method of water-borne hormone collection should be viable for many species of amphibians; however, further validation via adrenocorticotropic hormone (ACTH) challenges is required. This method can be a useful tool for assessing the physiological state of laboratory and field populations of amphibians and the effects of urbanization, pesticides and diseases. An important benefit of this method is that it allows for repeated measures of the same individuals and can be less stressful than drawing blood.
Rapid enigmatic decline drives the fire salamander (Salamandra salamandra) to the edge of extinction in the Netherlands
Authors: Spitzen-van der Sluijs Annemarieke , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , de Zeeuw Marnix , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , de Zeeuw Marnix , van der Meij Tom , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , de Zeeuw Marnix , van der Meij Tom , Goverse Edo , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , de Zeeuw Marnix , van der Meij Tom , Goverse Edo , Kik Marja , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , de Zeeuw Marnix , van der Meij Tom , Goverse Edo , Kik Marja , Pasmans Frank , Spitzen-van der Sluijs Annemarieke , Spikmans Frank , Bosman Wilbert , de Zeeuw Marnix , van der Meij Tom , Goverse Edo , Kik Marja , Pasmans Frank , Martel An 
Published: November 2018

In the Netherlands, the fire salamander (Salamandra salamandra) is at the edge of its geographic range and is restricted to three small populations in the extreme south of the country. Despite the species being listed as ‘Endangered’ on the national Red List, the situation was considered to be stable. However, from 2008 onwards dead individuals were seen on more than one occasion. A sharp decline in numbers has been observed since 2010 (96%; ), but we were unable to attribute this to any known cause of amphibian decline, such as chytridiomycosis, ranavirus or habitat degradation. The present work describes this enigmatic decline, and we discuss these results in the context of possible causes.
The taxonomic history of the enigmatic Papuan snake genus Toxicocalamus (Elapidae: Hydrophiinae), with the description of a new species from the Managalas Plateau of Oro Province, Papua New Guinea, and a revised dichotomous key
Authors: O’Shea Mark , Allison Allen , Kaiser Hinrich 
Published: November 2018

Abstract
We trace the taxonomic history of Toxicocalamus, a poorly known genus of primarily vermivorous snakes found only in New Guinea and associated island archipelagos. With only a relatively limited number of specimens to examine, and the distribution of those specimens across many natural history collections, it has been a difficult task to assemble a complete taxonomic assessment of this group. As a consequence, research on these snakes has undergone a series of fits and starts, and we here present the first comprehensive chronology of the genus, beginning with its original description by George Albert Boulenger in 1896. We also describe a new species from the northern versant of the Owen Stanley Range, Oro Province, Papua New Guinea, and we present a series of comparisons that include heretofore underused characteristics, including those of unusual scale patterns, skull details, and tail tip morphology. Defined by the smallest holotype in the genus, the new species is easily differentiated from all other Toxicocalamus by a combination of the following eidonomic characters: fused prefrontal-internasal scute; single preocular, separate, not fused with prefrontal; minute circular, counter-sunk naris in the centre of a large, undivided, nasal scute; paired postoculars; single anterior temporal and paired posterior temporals; six supralabials, with 3rd and 4th supralabial contacting the orbit; dorsal scales in 15-15-15 rows; 235 ventral scales, 35 paired subcaudal scales; paired cloacal scales preceded by paired precloacal scales; and a short, laterally slightly compressed, ‘Ultrocalamus-type’ tail, terminating in a short conical scale. Differences from congeners in skull morphology include a reduced anterior extent of the parasphenoid, termination of the palatine tooth row at the anterior level of the parasphenoid, extent and shape of the premaxilla, shape and size of the prootics, extent and shape of the exoccipitals and occipital condyles, and features of the atlas-axis complex. This is the fifteenth species in the genus Toxicocalamus.
Play fighting in Visayan warty pigs (Sus cebifrons): insights on restraint and reciprocity in the maintenance of play
Authors: Pellis Sergio M. , Pellis Vivien C. 
Published: November 2018

Restraint is thought to be essential to enable the reciprocity needed for play fighting to remain playful. Descriptions of playing in pigs suggest that they do not exhibit restraint. Analysis of videotaped sequences of play fighting in captive family groups of warty pigs was used to test three hypotheses about restraint and reciprocity. Hypothesis 1 asserts that the lack of restraint arises from neither participant handicapping its actions in favour of its opponent: this was supported. Hypothesis 2 asserts that the winner of a contest will show restraint by not prosecuting further attack: this was not supported. However, the winner did refrain from attacking if the loser signalled submission. Hypothesis 3 asserts that restraint by the winner will allow reciprocal attacks by the loser — this was supported. The dissociation of restraint and reciprocity evident in the pigs offers some new insights into the evolution of play fighting.
Birds of a feather? Parrot and corvid cognition compared
Authors: Lambert Megan L. , Jacobs Ivo , Osvath Mathias , von Bayern Auguste M.P. 
Published: November 2018

Abstract
The last several decades of research on avian cognition have revealed surprising parallels between the abilities of birds — most notably corvids — and great apes. Parrots, albeit far less studied, are cited alongside corvids as “feathered apes”, but are these two taxa really that similar cognitively? In this review we aim to take a step back and present the broader picture, focusing on areas where there is now data from both parrots and corvids to facilitate first comparisons on a somewhat wider scale. By charting these birds’ performance in cognitive tasks, in many of which corvids perform on par with primates, we hope to highlight understudied areas and promising directions for future research. In reviewing the literature, the general pattern that emerges shows that different corvid and parrot species indeed perform similarly in a range of cognitive tasks to the extent that one may call them “feathered apes”.
Description of Aphelenchoides tabarestanensis n. sp. (Nematoda: Aphelenchoididae) isolated from Pinus brutia in Northern Iran
Authors: Golhasan Behrouz , Fang Yiwu , Li Hongmei , Tanha Maafi Zahra , Heydari Ramin 
Published: November 2018

Summary
Aphelenchoides tabarestanensis n. sp. was isolated during a survey of nematodes associated with bark samples of pine trees (Pinus brutia) in Mazandaran province, northern Iran. The new species is characterised by body length of 656 (580-786) μm (females) and 490 (480-500) μm (males), weakly annulated cuticle, four lines in the lateral field, and an offset lip region. The stylet is 10.5 (10-11) μm long and has small basal swellings. The excretory pore is located at nerve ring level and the hemizonid was not seen. The post-vulval uterine sac is 40.8 (38-43) μm long, the spicules are relatively short (18-19 μm in dorsal limb), and the male tail has the usual three pairs of caudal papillae (2 + 2 + 2). The female tail is subcylindrical with two or three minute processes at the tip. The new species belongs to the Group 3 category of Aphelenchoides species and is close to seven known species of the genus, namely: A. asteromucronatus, A. besseyi, A. fujianensis, A. goodeyi, A. ritzemabosi, A. siddiqii, and A. stellatus, but differs by body size, shape of tail mucron, stylet length, size of spicules, and length of post-vulval uterine sac. Phylogenetic analysis based on small subunit (SSU) and partial large subunit (LSU) sequences of rRNA supported the morphological results.
Bursaphelenchus carpini n. sp., B. laciniatae n. sp. and B. cryphali okhotskensis n. subsp. (Nematoda: Aphelenchoididae) isolated from Japan
Authors: Kanzaki Natsumi , Masuya Hayato , Ichihara Yu , Maehara Noritoshi , Aikawa Takuya , Ekino Taisuke , Ide Tatsuya 
Published: November 2018

Summary
Two new species and a new subspecies of Bursaphelenchus are described. Bursaphelenchus carpini n. sp. and B. cryphali okhotskensis n. subsp. were isolated from Cryphalus carpini emerged from a dead log of a Carpinus sp. collected in Ibaraki Prefecture, Japan, and from C. piceae emerged from a dead log of Abies sachalinensis collected in Hokkaido, Japan, respectively. Meanwhile, B. laciniatae n. sp. was isolated from the bark of dead Ulmus laciniata, which harboured Scolytus esuriens galleries, collected in Hokkaido, Japan. These three species phylogenetically belong to the eggersi/eremus-group clade and share common typological characters such as a relatively slender body, three-lined lateral field, male spicule with a well-developed condylus, short and wide blade (calomus-lamina complex) and lack of clear cucullus. These three species and subspecies can be distinguished from one another and their close relatives by the condylus shape, female tail shape and phylogenetic and biological characters.