bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reevaluating the Risk of Smallpox Reemergence
Authors: MacIntyre C Raina 
Published: May 2020

Abstract

Introduction
Smallpox, caused by variola virus, was eradicated in 1980, but remains a category A bioterrorism agent. A decade ago, smallpox ranked second after anthrax in a multifactorial risk priority scoring analysis of category A bioterrorism agents. However, advances in genetic engineering and synthetic biology, including published methods for synthesizing an Orthopoxvirus, require the assumptions of this scoring for smallpox and other category A agents to be reviewed.

Materials and Methods
The risk priority framework was reviewed and revised to account for the capability for creation of synthetic or engineered smallpox and other category A agents.

Results
The absolute score for all agents increased because of gene editing and synthetic biology capability, which was not present when the framework was developed more than a decade ago, although new treatments revised scores downward for smallpox, Ebola, and botulism. In the original framework, smallpox scored 0 for global availability, given the high security around known seed stocks of variola in two laboratories in the United States and Russia. Now, smallpox can be created using synthetic biology, raising the score for this criterion to 2. Other agents too, such as Ebola, score higher for availability, based on synthetic biology capability. When advances in synthetic biology and genetic engineering are considered, smallpox and anthrax are now equally ranked the highest category A bioterrorism agents for planning and preparedness.

Conclusions
Revision of a risk priority framework for category A bioterrorism agents shows that smallpox should be elevated in priority for preparedness planning, and that gene editing and synthetic biology raises the overall risk for all agents. The ranking of categories A, B, and C agents should also be revisited, as there is an endless possibility of engineered threats that may be more severe than any agent on the category A list.
Implementing Evidence-Based Practice Facilitators: A Case Series
Authors: Augustino Leslie R , Braun Lisa , Heyne Rebecca E , Shinn Antoinette , Lovett-Floom LeAnne , King Heather , Brackett Ceferina , Migliore Laurie , Hatzfeld Jennifer 
Published: May 2020

Abstract

Background
In 2017, the TriService Nursing Research Program completed a strategic planning session, which identified key barriers to implementing evidence-based practice (EBP) within the U.S. Military Health System (MHS) including a focus on readiness training and deployments, frequent staff moves for military members, and relatively junior nurses in clinical roles. To facilitate EBP at individual military treatment facilities (MTFs), an EPB Facilitator role was developed using an evidence-based model and based on validated EBP competencies.

Methods
This new role was implemented at four MTFs in 2018: Naval Medical Center Portsmouth, 59th Medical Wing at Joint Base San Antonio Lackland, Naval Medical Center San Diego, and David Grant USAF Medical Center at Travis Air Force Base. This case series provides a description of the initial implementation of this role.

Results
Common enablers and challenges were identified from the experiences at all four sites. These included the importance of incorporating efforts into existing organizational efforts and infrastructure; the value of nurse leaders inviting EBP facilitators to participate and engage in scheduled meetings and committees; the significance of engaging with existing quality, process improvement, and training initiatives; and the benefit of collaborating with advanced practice nurses within the organization. The common challenges for all EBP facilitators were the frequent staff turnover at all levels and a lack of standardization to review and approve EBP initiatives, which makes it difficult to navigate the complete process of project implementation and collaboration across sites. Another challenge has been the difficulty to measure the impact of this role at the MTF and MHS levels.

Conclusions
As EBP efforts continue and the program matures, it is anticipated that the outcomes from the individually completed projects, to include decreases in safety events, fiscal savings, and other improvements in organizational metrics, can be compiled to demonstrate the collective impact of these roles within the MHS.
Determination of magnetic field strength on the event horizon of supermassive black holes in active galactic nuclei
Authors: Piotrovich M Yu , Mikhailov A G , Buliga S D , Natsvlishvili T M 
Published: May 2020

ABSTRACT
We estimated the magnetic field strength at the event horizon for a sample of supermassive black holes (SMBHs) in active galactic nuclei (AGNs). Our estimates were made using the values of the inclination angles of the accretion disc to the line of sight, which we obtained previously from spectropolarimetric observations in the visible spectrum. We also used published values of full width at half-maximum of spectral line Hβ from broad-line region, masses of SMBHs, and luminosity of AGNs at 5100 $\mathring{\rm A}$. In addition, we used the literature data on the spins of SMBHs obtained from their X-ray spectra. Our estimates showed that the magnetic field strength at the event horizon of the majority of SMBHs in AGNs range from several to tens of kG and have mean values of about 104 G. At the same time, for individual objects, the fields are significantly larger – of the order of hundreds kG or even 1 MG.
Increasing accuracy of HLA imputation by a population-specific reference panel in a FinnGen biobank cohort
Authors: Ritari Jarmo , Hyvärinen Kati , Clancy Jonna ,   FinnGen, Partanen Jukka , Koskela Satu 
Published: May 2020

Abstract
The HLA genes, the most polymorphic genes in the human genome, constitute the strongest single genetic susceptibility factor for autoimmune diseases, transplantation alloimmunity and infections. HLA imputation via statistical inference of alleles based on single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with alleles is a powerful first-step screening tool. Due to different LD structures between populations, the accuracy of HLA imputation may benefit from matching the imputation reference with the study population. To evaluate the potential advantage of using population-specific reference in HLA imputation, we constructed an HLA reference panel consisting of 1150 Finns with 5365 major histocompatibility complex region SNPs consistent between genome builds. We evaluated the accuracy of the panel against a European panel in an independent test set of 213 Finnish subjects. We show that the Finnish panel yields a lower imputation error rate (1.24% versus 1.79%). More than 30% of imputation errors occurred in haplotypes enriched in Finland. The frequencies of imputed HLA alleles were highly correlated with clinical-grade HLA allele frequencies and allowed accurate replication of established HLA–disease associations in ∼102 000 biobank participants. The results show that a population-specific reference increases imputation accuracy in a relatively isolated population within Europe and can be successfully applied to biobank-scale genome data collections.
Identification and analysis of consensus RNA motifs binding to the genome regulator CTCF
Authors: Kuang Shuzhen , Wang Liangjiang 
Published: May 2020

AbstractCCCTC-binding factor (CTCF) is a key regulator of 3D genome organization and gene expression. Recent studies suggest that RNA transcripts, mostly long non-coding RNAs (lncRNAs), can serve as locus-specific factors to bind and recruit CTCF to the chromatin. However, it remains unclear whether specific sequence patterns are shared by the CTCF-binding RNA sites, and no RNA motif has been reported so far for CTCF binding. In this study, we have developed DeepLncCTCF, a new deep learning model based on a convolutional neural network and a bidirectional long short-term memory network, to discover the RNA recognition patterns of CTCF and identify candidate lncRNAs binding to CTCF. When evaluated on two different datasets, human U2OS dataset and mouse ESC dataset, DeepLncCTCF was shown to be able to accurately predict CTCF-binding RNA sites from nucleotide sequence. By examining the sequence features learned by DeepLncCTCF, we discovered a novel RNA motif with the consensus sequence, AGAUNGGA, for potential CTCF binding in humans. Furthermore, the applicability of DeepLncCTCF was demonstrated by identifying nearly 5000 candidate lncRNAs that might bind to CTCF in the nucleus. Our results provide useful information for understanding the molecular mechanisms of CTCF function in 3D genome organization.
Phase II study of peginterferon alpha-2b for patients with unresectable or recurrent craniopharyngiomas: a Pediatric Brain Tumor Consortium report
Authors: Goldman Stewart , Pollack Ian F , Jakacki Regina I , Billups Catherine A , Poussaint Tina Y , Adesina Adekunle M , Panigrahy Ashok , Parsons Donald W , Broniscer Alberto , Robinson Giles W , Robison Nathan J , Partap Sonia , Kilburn Lindsay B , Onar-Thomas Arzu , Dunkel Ira J , Fouladi Maryam 
Published: May 2020

AbstractBackgroundCraniopharyngiomas account for approximately 1.2–4% of all CNS tumors. They are typically treated with a combination of surgical resection and focal radiotherapy. Unfortunately, treatment can lead to permanent deleterious effects on behavior, learning, and endocrine function.MethodsThe Pediatric Brain Tumor Consortium performed a multicenter phase 2 study in children and young adults with unresectable or recurrent craniopharyngioma (PBTC-039). Between December 2013 and November 2017, nineteen patients (median age at enrollment, 13.1 y; range, 2–25 y) were enrolled in one of 2 strata: patients previously treated with surgery alone (stratum 1) or who received radiation (stratum 2).ResultsEighteen eligible patients (8 male, 10 female) were treated with weekly subcutaneous pegylated interferon alpha-2b for up to 18 courses (108 wk). Therapy was well tolerated with no grade 4 or 5 toxicities. 2 of the 7 eligible patients (28.6%) in stratum 1 had a partial response, but only one response was sustained for more than 3 months. None of the 11 stratum 2 patients had an objective radiographic response, although median progression-free survival was 19.5 months.ConclusionsPegylated interferon alpha-2b treatment, in lieu of or following radiotherapy, was well tolerated in children and young adults with recurrent craniopharyngiomas. Although objective responses were limited, progression-free survival results are encouraging, warranting further studies.
Validation of diffusion MRI phenotypes for predicting response to bevacizumab in recurrent glioblastoma: post-hoc analysis of the EORTC-26101 trial
Authors: Schell Marianne , Pflüger Irada , Brugnara Gianluca , Isensee Fabian , Neuberger Ulf , Foltyn Martha , Kessler Tobias , Sahm Felix , Wick Antje , Nowosielski Martha , Heiland Sabine , Weller Michael , Platten Michael , Maier-Hein Klaus H , Von Deimling Andreas , Van Den Bent Martin J , Gorlia Thierry , Wick Wolfgang , Bendszus Martin , Kickingereder Philipp 
Published: May 2020

Abstract

Background
This study validated a previously described diffusion MRI phenotype as a potential predictive imaging biomarker in patients with recurrent glioblastoma receiving bevacizumab (BEV).

Methods
A total of 396/596 patients (66%) from the prospective randomized phase II/III EORTC-26101 trial (with n = 242 in the BEV and n = 154 in the non-BEV arm) met the inclusion criteria with availability of anatomical and diffusion MRI sequences at baseline prior treatment. Apparent diffusion coefficient (ADC) histograms from the contrast-enhancing tumor volume were fitted to a double Gaussian distribution and the mean of the lower curve (ADClow) was used for further analysis. The predictive ability of ADClow was assessed with biomarker threshold models and multivariable Cox regression for overall survival (OS) and progression-free survival (PFS).

Results
ADClow was associated with PFS (hazard ratio [HR] = 0.625, P = 0.007) and OS (HR = 0.656, P = 0.031). However, no (predictive) interaction between ADClow and the treatment arm was present (P = 0.865 for PFS, P = 0.722 for OS). Independent (prognostic) significance of ADClow was retained after adjusting for epidemiological, clinical, and molecular characteristics (P ≤ 0.02 for OS, P ≤ 0.01 PFS). The biomarker threshold model revealed an optimal ADClow cutoff of 1241*10–6 mm2/s for OS. Thereby, median OS for BEV-patients with ADClow ≥ 1241 was 10.39 months versus 8.09 months for those with ADClow &lt; 1241 (P = 0.004). Similarly, median OS for non-BEV patients with ADClow ≥ 1241 was 9.80 months versus 7.79 months for those with ADClow &lt; 1241 (P = 0.054).

Conclusions
ADClow is an independent prognostic parameter for stratifying OS and PFS in patients with recurrent glioblastoma. Consequently, the previously suggested role of ADClow as predictive imaging biomarker could not be confirmed within this phase II/III trial.
Successful intervention for overwhelming postsplenectomy infection caused by non-vaccine pneumococcal serotype 23A
Authors: Kojima Yuichi , Ikeda Kazuna , Matsumura Akihiro , Shimohama Shun , Chang Bin , Yoshida Takayuki , Hamada Kunio , Ito Akihide , Ito Toshiki 
Published: May 2020

Abstract
The spleen plays an important role in the body’s immune defense against invasive infections, particularly those caused by encapsulated bacteria. Encapsulated bacterial infection in asplenic patients is a medical emergency called overwhelming postsplenectomy infection (OPSI) and has a mortality rate of 50–70%. Here, we report the case of a 51-year-old Asian man who complained of emesis and diarrhea as primary symptoms. He rapidly progressed to coma and was eventually diagnosed with OPSI (pyogenic ventriculitis/spondylitis) caused by non-vaccine pneumococcal serotype 23A. Aggressive management, including empiric antibiotic therapy, a staircase approach for intracranial pressure-targeted therapy and laminectomy/laminoplasty, resulted in a good recovery. Our report highlights that non-vaccine pneumococcal serotypes can cause disease in vaccinated patients.
High-mass star formation in Orion B triggered by cloud–cloud collision: Merging molecular clouds in NGC 2024
Authors: Enokiya Rei , Ohama Akio , Yamada Rin , Sano Hidetoshi , Fujita Shinji , Hayashi Katsuhiro , Tsutsumi Daichi , Torii Kazufumi , Nishimura Atsushi , Konishi Ryotaro , Yamamoto Hiroaki , Tachihara Kengo , Hasegawa Yutaka , Kimura Kimihiro , Ogawa Hideo , Fukui Yasuo 
Published: May 2020

AbstractWe performed new comprehensive 13CO(J = 2–1) observations toward NGC 2024, the most active star-forming region in Orion B, with an angular resolution of ∼100″ obtained with Nanten2. We found that the associated cloud consists of two independent velocity components. The components are physically connected to the H ii region as evidenced by their close correlation with the dark lanes and the emission nebulosity. The two components show complementary distribution with a displacement of ∼0.6 pc. Such complementary distribution is typical to colliding clouds discovered in regions of high-mass star formation. We hypothesize that a cloud–cloud collision between the two components triggered the formation of the late O-type stars and early B stars localized within 0.3 pc of the cloud peak. The duration time of the collision is estimated to be 0.3 million years from a ratio of the displacement and the relative velocity ∼3 km s−1 corrected for probable projection. The high column density of the colliding cloud ∼1023 cm−2 is similar to those in the other high-mass star clusters in RCW 38, Westerlund 2, NGC 3603, and M 42, which are likely formed under trigger by cloud–cloud collision. The present results provide an additional piece of evidence favorable to high-mass star formation by a major cloud–cloud collision in Orion.
Employment trajectories and health: cohort differences in English and French women
Authors: Zella Sara , Harper Sarah 
Published: May 2020

ABSTRACT

Background
Policy and social change have increased women’s participation in the labour market and their opportunity to combine paid work with family care. We analyse whether a specific combination of employment and domestic duties over the life course are associated with variations in English and French women’s health, focusing on two birth cohorts.

Methods
We used sequence analysis to group women in English Longitudinal Study of Ageing and Survey of Health, Ageing and Retirement in Europe, according to their work and family histories. Using ordered logistic regression, we tested for group differences in later self-reported health and depressive symptoms, while controlling for a range of adult socio-economic circumstances.

Results
The findings confirm important differences between birth cohorts and countries. French women report a higher risk of poor self-reported health and mental issues than English women. Full-time domestic duties were particularly deleterious for the health of the two younger cohorts, whereas a combination of employment and domestic duties across the life course had a positive association with later-life health.

Discussion
Further research is needed to explore the mechanisms linking work and care trajectories to poor health.
CAPM-Based Company (Mis)valuations
Authors: Dessaint Olivier , Olivier Jacques , Otto Clemens A , Thesmar David 
Published: May 2020

Abstract
There is a discrepancy between CAPM-implied and realized returns. Using the CAPM in capital budgeting—as recommended in textbooks—should thus have real effects. For instance, low beta projects should be valued more by CAPM users than by the market. We test this hypothesis using M&A data and show that bids for low-beta private targets entail lower bidder returns. We provide further support by testing several ancillary predictions. Our analyses suggest that using the CAPM when valuing targets leads to valuation errors (relative to the market’s view) corresponding on average to 12% to 33% of the deal values.
NLRP12 gene mutations and auto-inflammatory diseases: ever-changing evidence
Authors: Del Porto Flavia , Cifani Noemi , Proietta Maria , Verrecchia Elena , Di Rosa Roberta , Manna Raffaele , Chiurazzi Pietro 
Published: May 2020

Abstract
Systemic auto-inflammatory diseases (SAID) are a group of rare inherited conditions characterized by a dysregulation of the immune system and associated with recurrent episodes of fever and systemic inflammation. Patients with NLRP12 variants develop a rare autosomal dominant condition known as familial cold-induced autoinflammatory syndrome (FCAS2, OMIM #611762) that has been related to several different clinical manifestations including autoimmunity and immune deficiencies. In past years, several new variants have been described; however, their clinical relevance is sometimes uncertain, especially when they have been detected in healthy subjects. To our knowledge 61 patients with NLRP12 variants have been reported so far in the literature. Here we report the case of a 33-year-old woman with a history of recurrent fever and symmetric and additive poly-arthritis, fulfilling diagnostic criteria for RA, who was found to harbour two variants in the NLRP12 gene (OMIM *609648) and provide a review of the literature on similar cases.
Cortical Gyrification, Psychotic-Like Experiences, and Cognitive Performance in Nonclinical Subjects
Authors: Evermann Ulrika , Gaser Christian , Besteher Bianca , Langbein Kerstin , Nenadić Igor 
Published: May 2020

AbstractBackgroundPsychotic-like experiences (PLE) are present in nonclinical populations, yet their association with brain structural variation, especially markers of early neurodevelopment, is poorly understood. We tested the hypothesis that cortical surface gyrification, a putative marker of early brain development, is associated with PLE in healthy subjects.MethodsWe analyzed gyrification from 3 Tesla MRI scans (using CAT12 software) and PLE (positive, negative, and depressive symptom dimensions derived from the Community Assessment of Psychic Experiences, CAPE) in 103 healthy participants (49 females, mean age 29.13 ± 9.37 years). A subsample of 63 individuals completed tasks from the Wechsler Adult Intelligence Scale and Controlled Oral Word Association Test. Estimated IQ and a composite neuropsychological score were used to explore mediation pathways via cognition.ResultsPositive PLE distress was negatively associated with gyrification of the left precuneus. PLE depression dimension showed a negative association with gyrification in the right supramarginal and temporal region. There was no significant mediating effect of cognition on these associations.ConclusionOur results support a neurobiological psychosis spectrum, for the first time linking an early developmental imaging marker (rather than volume) to dimensional subclinical psychotic symptoms. While schizophrenia risk, neurodevelopment, and cognitive function might share genetic risk factors, additional mediation analyses did not confirm a mediating effect of cognition on the gyrification-psychopathology correlation.
Hypotension after spinal anesthesia for cesarean section: how to approach the iatrogenic sympathectomy
Authors: Massoth Christina , Töpel Lisa , Wenk Manuel 
Published: May 2020

Purpose of review
Hypotension during cesarean section remains a frequent complication of spinal anesthesia and is associated with adverse maternal and fetal events.

Recent findings
Despite ongoing research, no single measure for sufficient treatment of spinal-induced hypotension was identified so far. Current literature discusses the efficacy of low-dose spinal anesthesia, timing and solutions for adequate fluid therapy and various vasopressor regimens. Present guidelines favor the use of phenylephrine over ephedrine because of decreased umbilical cord pH values, while norepinephrine is discussed as a probable superior alternative with regard to maternal bradycardia, although supporting data is limited. Alternative pharmacological approaches, such as 5HT3-receptor antagonists and physical methods may be taken into consideration to further improve hemodynamic stability.

Summary
Current evidence favors a combined approach of low-dose spinal anesthesia, adequate fluid therapy and vasopressor support to address maternal spinal-induced hypotension. As none of the available vasopressors is associated with relevantly impaired maternal and fetal outcomes, none of them should be abandoned from obstetric practice. Rapid crystalloid co-loading is of equivalent efficacy as compared with colloids and should be preferred because of a more favorable risk profile.