bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Near-Complete Haplotype-Phased Genome of the Dikaryotic Wheat Stripe Rust FungusPuccinia striiformisf. sp.triticiReveals High Interhaplotype Diversity
Authors: Schwessinger Benjamin , Sperschneider Jana , Cuddy William S. , Garnica Diana P. , Miller Marisa E. , Taylor Jennifer M. , Dodds Peter N. , Figueroa Melania , Park Robert F. , Rathjen John P. 
Published: February 2018

ABSTRACTA long-standing biological question is how evolution has shaped the genomic architecture of dikaryotic fungi. To answer this, high-quality genomic resources that enable haplotype comparisons are essential. Short-read genome assemblies for dikaryotic fungi are highly fragmented and lack haplotype-specific information due to the high heterozygosity and repeat content of these genomes. Here, we present a diploid-aware assembly of the wheat stripe rust fungusPuccinia striiformisf. sp.triticibased on long reads using the FALCON-Unzip assembler. Transcriptome sequencing data sets were used to infer high-quality gene models and identify virulence genes involved in plant infection referred to as effectors. This represents the most completePuccinia striiformisf. sp.triticigenome assembly to date (83 Mb, 156 contigs,N50of 1.5 Mb) and provides phased haplotype information for over 92% of the genome. Comparisons of the phase blocks revealed high interhaplotype diversity of over 6%. More than 25% of all genes lack a clear allelic counterpart. When we investigated genome features that potentially promote the rapid evolution of virulence, we found that candidate effector genes are spatially associated with conserved genes commonly found in basidiomycetes. Yet, candidate effectors that lack an allelic counterpart are more distant from conserved genes than allelic candidate effectors and are less likely to be evolutionarily conserved within theP. striiformisspecies complex andPucciniales. In summary, this haplotype-phased assembly enabled us to discover novel genome features of a dikaryotic plant-pathogenic fungus previously hidden in collapsed and fragmented genome assemblies.IMPORTANCECurrent representations of eukaryotic microbial genomes are haploid, hiding the genomic diversity intrinsic to diploid and polyploid life forms. This hidden diversity contributes to the organism’s evolutionary potential and ability to adapt to stress conditions. Yet, it is challenging to provide haplotype-specific information at a whole-genome level. Here, we take advantage of long-read DNA sequencing technology and a tailored-assembly algorithm to disentangle the two haploid genomes of a dikaryotic pathogenic wheat rust fungus. The two genomes display high levels of nucleotide and structural variations, which lead to allelic variation and the presence of genes lacking allelic counterparts. Nonallelic candidate effector genes, which likely encode important pathogenicity factors, display distinct genome localization patterns and are less likely to be evolutionary conserved than those which are present as allelic pairs. This genomic diversity may promote rapid host adaptation and/or be related to the age of the sequenced isolate since last meiosis.
Factors associated with insufficient awareness of breast cancer among women in Northern and Eastern China: a case–control study
Authors: Liu Li-Yuan , Wang Yong-Jiu , Wang Fei , Yu Li-Xiang , Xiang Yu-Juan , Zhou Fei , Li Liang , Zhang Qiang , Fu Qin-Ye , Ma Zhong-Bing , Gao De-Zong , Li Yu-Yang , Yu Zhi-Gang 
Published: February 2018

ObjectivesTo investigate the awareness and knowledge level of breast cancer among Chinese participants.DesignCase–control study.SettingsThis study was based on the database of the minister-affiliated hospital key project of the Ministry of Health of the People’s Republic of China that included 21 Chinese hospitals between April 2012 and April 2013.ParticipantsMatched study was designed among 2978 participants with Han ethnicity aged between 25 and 70.Primary and secondary outcome measuresStudent’s t-test, Pearson’s χ2test, reliability analysis, exploratory factor analysis, and univariate and multivariate logistic regression analyses were performed to know the level of breast cancer knowledge and find the breast cancer awareness-associated factors.Results80.0% (2383/2978) of the participants had poor awareness level of breast cancer. In-depth knowledge of breast cancer such as early symptoms and risk factors was poorly found among them. Television broadcast and relatives or friends with breast cancers were the main sources of information about breast cancer. Of all participants, 72.8% (2167/2978) had heard about breast cancer as a frequent cancer affecting women, and 63.3% (1884/2978) knew that family history of breast cancer was a risk factor for breast cancer. Over half of them were aware that a breast lump could be a symptom of breast cancer. Multivariate analysis identified the following variables that predicted awareness of breast cancer: young age (OR=0.843, 95% CI 0.740 to 0.961), occupation (agricultural worker) (OR=12.831, 95% CI 6.998 to 23.523), high household social status (OR=0.644, 95% CI 0.531 to 0.780), breast hyperplasia history (OR=1.684, 95% CI 1.273 to 2.228), high behavioural prevention score (OR=4.407, 95% CI 3.433 to 5.657).ConclusionMost women were aware of breast cancer as a disease, but their in-depth knowledge of it was poor. More publicity and education programmes to increase breast cancer awareness are necessary and urgent, especially for the ageing women and agricultural workers.
Making soft intelligence hard: a multi-site qualitative study of challenges relating to voice about safety concerns
Authors: Martin Graham P , Aveling Emma-Louise , Campbell Anne , Tarrant Carolyn , Pronovost Peter J , Mitchell Imogen , Dankers Christian , Bates David , Dixon-Woods Mary 
Published: February 2018

BackgroundHealthcare organisations often fail to harvest and make use of the ‘soft intelligence’ about safety and quality concerns held by their own personnel. We aimed to examine the role of formal channels in encouraging or inhibiting employee voice about concerns.MethodsQualitative study involving personnel from three academic hospitals in two countries. Interviews were conducted with 165 participants from a wide range of occupational and professional backgrounds, including senior leaders and those from the sharp end of care. Data analysis was based on the constant comparative method.ResultsLeaders reported that they valued employee voice; they identified formal organisational channels as a key route for the expression of concerns by employees. Formal channels and processes were designed to ensure fairness, account for all available evidence and achieve appropriate resolution. When processed through these formal systems, concerns were destined to become evidenced, formal and tractable to organisational intervention. But the way these systems operated meant that some concerns were never voiced. Participants were anxious about having to process their suspicions and concerns into hard evidentiary facts, and they feared being drawn into official procedures designed to allocate consequence. Anxiety about evidence and process was particularly relevant when the intelligence was especially ‘soft’—feelings or intuitions that were difficult to resolve into a coherent, compelling reconstruction of an incident or concern. Efforts to make soft intelligence hard thus risked creating ‘forbidden knowledge’: dangerous to know or share.ConclusionsThe legal and bureaucratic considerations that govern formal channels for the voicing of concerns may, perversely, inhibit staff from speaking up. Leaders responsible for quality and safety should consider complementing formal mechanisms with alternative, informal opportunities for listening to concerns.
Selection bias, interventions and outcomes for survivors of cardiac arrest
Authors: Wallace David J , Coppler Patrick , Callaway Clifton , Rittenberger Jon C , Dezfulian Cameron , Mohan Deepika , Toma Catalin , Elmer Jonathan 
Published: February 2018

ObjectiveCardiac catheterisation and implantable cardioverter defibrillator (ICD) insertion are increasingly common following cardiac arrest survival. However, much of the evidence for the benefit is observational, leaving open the possibility that biased patient selection confounds the association between these invasive procedures and improved outcome. We evaluated the likelihood of selection bias in the association between cardiac catheterisation or ICD placement and outcome by measuring long-term outcomes overall and in a cause-specific approach that separated cardiac mortality from non-cardiac mortality.MethodsWe performed a multivariable survival analysis of a clinical cohort between 2005 and 2013, with follow-up through 2015. We included patients who had out-of-hospital or inhospital cardiac arrest that survived to discharge, and evaluated the association between cardiac catheterisation or ICD insertion and all-cause, cardiovascular and non-cardiovascular mortality.ResultsAmong 678 patients who survived cardiac arrest, we observed lower all-cause mortality among patients who underwent cardiac catheterisation (adjusted HR (aHR) 0.40; P<0.01) or ICD insertion (aHR 0.55; P<0.01). However, cause-specific analysis showed that the benefits of cardiac catheterisation and ICD insertion resulted from reduced non-cardiac causes of death (cardiac catheterisation: aHR 0.24, P<0.01; ICD: aHR 0.58, P<0.01), while reduced cardiac cause of death was not associated with cardiac catheterisation (cardiac catheterisation: aHR 0.75, P=0.33).ConclusionsThere is evidence of selection bias in the secondary prevention survival benefit attributable to cardiac catheterisation for patients who survive cardiac arrest. Observational studies that consider its effects on all-cause mortality likely overestimate the potential benefit of this procedure.
Glaucoma awareness Indian military personnel: a tri-service study
Authors: Singh Atul Kumar , Pantola P , Khan M A , Tomar A , Dhabale V 
Published: February 2018

IntroductionIn India, glaucoma is the third most common cause of blindness, reflecting both its asymptomatic presentation and a lack of knowledge in the general population. No previous published data of glaucoma awareness among the Indian Armed forces personnel exists, who constitute a unique group consisting of people drawn from all parts of the country and society.MethodsBilingual questionnaires were distributed to 496 serving Army, Navy and Air Force personnel serving in units local to the Zonal military hospital in North India. Having heard of the term glaucoma resulted in the subject being ‘glaucoma aware’, while ‘knowledge of glaucoma’ required at least three out of six questions to be answered correctly.Results110/496 (22%) participants were found to be glaucoma aware, while knowledge of glaucoma was found in 60/496 (12%) participants.ConclusionsThis study demonstrates that glaucoma awareness and knowledge is high compared with rural or urban Indian populations. This is likely reflects the frequent health camps conducted by the armed forces and periodic medical examinations. However, these figures are still low compared with developed countries and likely reflects differences in education standards, socioeconomic status and differing influences of the media.
Proteolytic Release of the p75NTR Intracellular Domain by ADAM10 Promotes Metastasis and Resistance to Anoikis
Authors: Bao Xin , Shi Jianbo , Xie Furong , Liu Zengying , Yu Jingshuang , Chen Wantao , Zhang Zhiyuan , Xu Qin 
Published: February 2018

Abstract
Resistance to anoikis allows cancer cells to survive during systemic circulation; however, the mechanism underlying anoikis resistance remains unclear. Here we show that A disintegrin and metalloprotease 10 (ADAM10)–mediated cleavage of p75 neurotrophin receptor (p75NTR) and subsequent generation of the p75NTR intracellular domain (ICD) endow cancer cells with resistance to anoikis. p75NTR ICD promoted expression of TNF receptor–associated factor 6 (TRAF6), a critical intermediary in p75NTR ICD–mediated signal transduction, at the translational level. Cell detachment–induced activation of EGFR triggered autoubiquitination of TRAF6 by facilitating its dimerization, subsequently activated NFκB, and eventually led to anoikis resistance. ADAM10 and p75NTR ICD also promoted tumor metastasis formation in vivo. Together, our findings uncover a previously unknown function for the ADAM10-p75NTR ICD-TRAF6-NFκB axis in preventing anoikis and suggest ADAM10 and p75NTR ICD as potential cancer therapeutic targets.
Significance: These findings identify the ADAM10-p75NTR ICD-TRAF6-NFκB signaling axis as a potential candidate for cancer therapy. Cancer Res; 78(9); 2262–76. ©2018 AACR.
TGFβ1Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy
Authors: Tao Ye , Sturgis Erich M. , Huang Zhigang , Wang Ying , Wei Peng , Wang Jennifer Rui , Wei Qingyi , Li Guojun 
Published: February 2018

AbstractPurpose: TGFβ1 plays a critical role in inflammation and immune responses and treatment response and survival. TGFβ1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)–positive squamous cell carcinoma of the oropharynx (SCCOP).Experimental Design: We determined tumor HPV16 status and genotyped three TGFβ1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival.Results: Overall, 85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGFβ1 rs1982073 had statistically significant associations with survival, whereas TGFβ1 rs1800469 and TGFβ1 rs1800471 did not. Patients with TGFβ1 rs1982073 CT/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous TT genotype (all log-rank: P &lt; 0.001). Furthermore, these genotypes were significantly associated with an approximately 5 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Moreover, the stratified analyses by tumor HPV status indicated that the significant effects of TGFβ1 rs1982073 polymorphism on survival were found among HPV16-positive SCCOP patients only. Finally, the functional relevance of these variants was further characterized.Conclusions: Our findings support that the TGFβ1 rs1982073 polymorphism plays a significant role in the prognosis of SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings. Clin Cancer Res; 24(9); 2225–33. ©2018 AACR.
Prediction of the Optimal Dosing Regimen Using a Mathematical Model of Tumor Uptake for Immunocytokine-Based Cancer Immunotherapy
Authors: Ribba Benjamin , Boetsch Christophe , Nayak Tapan , Grimm Hans Peter , Charo Jehad , Evers Stefan , Klein Christian , Tessier Jean , Charoin Jean Eric , Phipps Alex , Pisa Pavel , Teichgräber Volker 
Published: February 2018

Abstract
Purpose: Optimal dosing is critical for immunocytokine-based cancer immunotherapy to maximize efficacy and minimize toxicity. Cergutuzumab amunaleukin (CEA-IL2v) is a novel CEA-targeted immunocytokine. We set out to develop a mathematical model to predict intratumoral CEA-IL2v concentrations following various systemic dosing intensities.
Experimental Design: Sequential measurements of CEA-IL2v plasma concentrations in 74 patients with solid tumors were applied in a series of differential equations to devise a model that also incorporates the peripheral concentrations of IL2 receptor–positive cell populations (i.e., CD8+, CD4+, NK, and B cells), which affect tumor bioavailability of CEA-IL2v. Imaging data from a subset of 14 patients were subsequently utilized to additionally predict antibody uptake in tumor tissues.
Results: We created a pharmacokinetic/pharmacodynamic mathematical model that incorporates the expansion of IL2R-positive target cells at multiple dose levels and different schedules of CEA-IL2v. Model-based prediction of drug levels correlated with the concentration of IL2R-positive cells in the peripheral blood of patients. The pharmacokinetic model was further refined and extended by adding a model of antibody uptake, which is based on drug dose and the biological properties of the tumor. In silico predictions of our model correlated with imaging data and demonstrated that a dose-dense schedule comprising escalating doses and shortened intervals of drug administration can improve intratumoral drug uptake and overcome consumption of CEA-IL2v by the expanding population of IL2R-positive cells.
Conclusions: The model presented here allows simulation of individualized treatment plans for optimal dosing and scheduling of immunocytokines for anticancer immunotherapy. Clin Cancer Res; 24(14); 3325–33. ©2018 AACR.
See related commentary by Ruiz-Cerdá et al., p. 3236
Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization
Authors: Piña Ileana L. , Zheng Qi , She Lilin , Szwed Hanna , Lang Irene M. , Farsky Pedro S. , Castelvecchio Serenella , Biernat Jolanta , Paraforos Alexandros , Kosevic Dragana , Favaloro Liliana E. , Nicolau José C. , Varadarajan Padmini , Velazquez Eric J. , Pai Ramdas G. , Cyrille Nicole , Lee Kerry L. , Desvigne-Nickens Patrice 
Published: February 2018

Background:
Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study).

Methods:
The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex.

Results:

At baseline, women were older (63.4 versus 59.3 years;
P
=0.016) with higher body mass index (27.9 versus 26.7 kg/m
2
;
P
=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all
P
<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all
P
<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52–0.86;
P
=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48–0.89;
P
=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all
P
>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%;
P
=0.187) between sexes among patients randomized to CABG per protocol as initial treatment.

Conclusions:
Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00023595.
First Pass Effect
Authors: Zaidat Osama O. , Castonguay Alicia C. , Linfante Italo , Gupta Rishi , Martin Coleman O. , Holloway William E. , Mueller-Kronast Nils , English Joey D. , Dabus Guilherme , Malisch Tim W. , Marden Franklin A. , Bozorgchami Hormozd , Xavier Andrew , Rai Ansaar T. , Froehler Michael T. , Badruddin Aamir , Nguyen Thanh N. , Taqi M. Asif , Abraham Michael G. , Yoo Albert J. , Janardhan Vallabh , Shaltoni Hashem , Novakovic Roberta , Abou-Chebl Alex , Chen Peng R. , Britz Gavin W. , Sun Chung-Huan J. , Bansal Vibhav , Kaushal Ritesh , Nanda Ashish , Nogueira Raul G. 
Published: February 2018

Background and Purpose—
In acute ischemic stroke, fast and complete recanalization of the occluded vessel is associated with improved outcomes. We describe a novel measure for newer generation devices: the first pass effect (FPE). FPE is defined as achieving a complete recanalization with a single thrombectomy device pass.

Methods—
The North American Solitaire Acute Stroke Registry database was used to identify a FPE subgroup. Their baseline features and clinical outcomes were compared with non-FPE patients. Clinical outcome measures included 90-days modified Rankin Scale score, National Institutes of Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage. Multivariate analyses were performed to determine whether FPE independently resulted in improved outcomes and to identify predictors of FPE.

Results—

A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354 (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer internal carotid artery occlusions (10.1% versus 27.7%) were present in the FPE group. Balloon guide catheters were used more frequently with FPE (64.0% versus 34.7%). Median time to revascularization was significantly faster in the FPE group (median 34 versus 60 minutes;
P
=0.0003). FPE was an independent predictor of good clinical outcome (modified Rankin Scale score ≤2 was seen in 61.3% in FPE versus 35.3% in non-FPE cohort;
P
=0.013; odds ratio, 1.7; 95% confidence interval, 1.1–2.7). The independent predictors of achieving FPE were use of balloon guide catheters and non-internal carotid artery terminus occlusion.

Conclusions—
The achievement of complete revascularization from a single Solitaire thrombectomy device pass (FPE) is associated with significantly higher rates of good clinical outcome. The FPE is more frequently associated with the use of balloon guide catheters and less likely to be achieved with internal carotid artery terminus occlusion.
“Only Surpassed by the Light of Revelation”
Authors: Beebe Ann 
Published: February 2018

Abstract
Asher B. Durand (1796–1886) began his long career in the Hudson River School under the guidance of his mentor, Thomas Cole (1801–1848). Influenced by the death of Cole in 1848 and other factors, Durand turned to the William Cullen Bryant poem, “Thanatopsis.” Durand’s Landscape—Scene from ‘Thanatopsis,’ an expansive allegory with a farmer and a funeral in the foreground illuminated by a sunrise, offers reassurance with its vision of nature’s paradisiacal beauty. The Christianized sublimity of this allegorical Durand painting reveals a hopeful vision for a heavenly paradise. This essay explores the significance of Durand’s 1850 painting in conjunction with Bryant’s “Thanatopsis,” a study Durand composed, Classical Landscape (Imaginary Landscape c. 1850), his 1855 Letters on Landscape Painting, as well as Durand’s 1862 repainting of the canvas.