bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and analytic considerations for using patient-reported health data in pragmatic clinical trials: report from an NIH Collaboratory roundtable
Authors: Rockhold Frank W , Tenenbaum Jessica D , Richesson Rachel , Marsolo Keith A , O’Brien Emily C 
Published: December 2019

Abstract
Pragmatic clinical trials often entail the use of electronic health record (EHR) and claims data, but bias and quality issues associated with these data can limit their fitness for research purposes particularly for study end points. Patient-reported health (PRH) data can be used to confirm or supplement EHR and claims data in pragmatic trials, but these data can bring their own biases. Moreover, PRH data can complicate analyses if they are discordant with other sources. Using experience in the design and conduct of multi-site pragmatic trials, we itemize the strengths and limitations of PRH data and identify situational criteria for determining when PRH data are appropriate or ideal to fill gaps in the evidence collected from EHRs. To provide guidance for the scientific rationale and appropriate use of patient-reported data in pragmatic clinical trials, we describe approaches for ascertaining and classifying study end points and addressing issues of incomplete data, data alignment, and concordance. We conclude by identifying areas that require more research.
Can we constrain the dark energy equation of state parameters using configuration entropy?
Authors: Das Biswajit , Pandey Biswajit 
Published: December 2019

ABSTRACT
We propose a new scheme for constraining the dark energy equation of state parameter/parameters based on the study of the evolution of the configuration entropy. We analyse a set of one-parameter and two-parameter dynamical dark energy models and find that the derivative of the configuration entropy in all the dynamical dark energy models exhibits a minimum. The magnitude of the minimum of the entropy rate is decided by both the parametrization of the equation of state and the associated parameters. The location of the minimum of the entropy rate is less sensitive to the form of the parametrization but depends on the associated parameters. We determine the best-fitting equations for the location and magnitude of the minimum of the entropy rate in terms of the parameter/parameters of the dark energy equation of state. These relations would allow us to constrain the dark energy equation of state parameter/parameters for any given parametrization provided the evolution of the configuration entropy in the Universe is known from observations.
The Pristine survey – IX. CFHT ESPaDOnS spectroscopic analysis of 115 bright metal-poor candidate stars
Authors: Venn Kim A , Kielty Collin L , Sestito Federico , Starkenburg Else , Martin Nicolas , Aguado David S , Arentsen Anke , Bonifacio Piercarlo , Caffau Elisabetta , Hill Vanessa , Jablonka Pascale , Lardo Carmela , Mashonkina Lyudmilla , Navarro Julio F , Sneden Chris , Thomas Guillaume , Youakim Kris , González-Hernández Jonay I , Sánchez Janssen Rubén , Carlberg Ray , Malhan Khyati 
Published: December 2019

ABSTRACT
A chemo-dynamical analysis of 115 metal-poor candidate stars selected from the narrow-band Pristine photometric survey is presented based on CFHT high-resolution ESPaDOnS spectroscopy. We have discovered 28 new bright (V &lt; 15) stars with [Fe/H] &lt; −2.5 and 5 with [Fe/H] &lt; −3.0 for success rates of 40 (28/70) and 19 per cent (5/27), respectively. A detailed model atmosphere analysis is carried out for the 28 new metal-poor stars. Stellar parameters were determined from SDSS photometric colours, Gaia DR2 parallaxes, MESA/MIST stellar isochrones, and the initial Pristine survey metallicities, following a Bayesian inference method. Chemical abundances are determined for 10 elements (Na, Mg, Ca, Sc, Ti, Cr, Fe, Ni, Y, and Ba). Most stars show chemical abundance patterns that are similar to the normal metal-poor stars in the Galactic halo; however, we also report the discoveries of a new r-process-rich star, a new CEMP-s candidate with [Y/Ba] &gt; 0, and a metal-poor star with very low [Mg/Fe]. The kinematics and orbits for all of the highly probable metal-poor candidates are determined by combining our precision radial velocities with Gaia DR2 proper motions. Some stars show unusual kinematics for their chemistries, including planar orbits, unbound orbits, and highly elliptical orbits that plunge deeply into the Galactic bulge (Rperi &lt; 0.5 kpc); also, eight stars have orbital energies and actions consistent with the Gaia-Enceladus accretion event. This paper contributes to our understanding of the complex chemo-dynamics of the metal-poor Galaxy, and increases the number of known bright metal-poor stars available for detailed nucleosynthetic studies.
The large amplitude X-ray variability in NGC 7589: possible evidence for accretion mode transition
Authors: Liu Zhu , Liu He-Yang , Cheng Huaqing , Qiao Erlin , Yuan Weimin 
Published: December 2019

ABSTRACT
We report the discovery of large amplitude X-ray variability in the low-luminosity active galactic nucleus NGC 7589, and present possible observational evidence for accretion mode transition in this source. Long-term X-ray flux variations by a factor of more than 50 are found using X-ray data obtained by Swift/X-Ray Telescope and XMM–Newton over 17 yr. Results of long-term monitoring data in the UV, optical, and infrared bands over ∼20 yr are also presented. The Eddington ratio λEdd increased from 10−3 to ∼0.13, suggesting a transition of the accretion flow from an advection dominated accretion flow to a standard thin accretion disc. Further evidence supporting the thin disc in the high-luminosity state is found by the detection of a significant soft X-ray component in the X-ray spectrum. The temperature of this component ($\sim 19^{+15}_{-7}$ eV, fitted with a blackbody model) is in agreement with the predicted temperature of the inner region for a thin disc around a black hole (BH) with mass of ∼107M⊙. These results may indicate that NGC 7589 had experienced accretion mode transition over a time-scale of a few years, suggesting the idea that similar accretion processes are at work for massive BH and BH X-ray binaries.
HSF2BP negatively regulates homologous recombination in DNA interstrand crosslink repair
Authors: Sato Koichi , Brandsma Inger , van Rossum-Fikkert Sari E , Verkaik Nicole , Oostra Anneke B , Dorsman Josephine C , van Gent Dik C , Knipscheer Puck , Kanaar Roland , Zelensky Alex N 
Published: December 2019

Abstract
The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability and DNA interstrand crosslink (ICL) repair in vertebrates. We show that ectopic production of HSF2BP, a BRCA2-interacting protein required for meiotic HR during mouse spermatogenesis, in non-germline human cells acutely sensitize them to ICL-inducing agents (mitomycin C and cisplatin) and PARP inhibitors, resulting in a phenotype characteristic of cells from Fanconi anemia (FA) patients. We biochemically recapitulate the suppression of ICL repair and establish that excess HSF2BP compromises HR by triggering the removal of BRCA2 from the ICL site and thereby preventing the loading of RAD51. This establishes ectopic expression of a wild-type meiotic protein in the absence of any other protein-coding mutations as a new mechanism that can lead to an FA-like cellular phenotype. Naturally occurring elevated production of HSF2BP in tumors may be a source of cancer-promoting genomic instability and also a targetable vulnerability.
DNA targeting by Clostridium cellulolyticum CRISPR–Cas9 Type II-C system
Authors: Fedorova Iana , Arseniev Anatolii , Selkova Polina , Pobegalov Georgii , Goryanin Ignatiy , Vasileva Aleksandra , Musharova Olga , Abramova Marina , Kazalov Maksim , Zyubko Tatyana , Artamonova Tatyana , Artamonova Daria , Shmakov Sergey , Khodorkovskii Mikhail , Severinov Konstantin 
Published: December 2019

Abstract
Type II CRISPR–Cas9 RNA-guided nucleases are widely used for genome engineering. Type II-A SpCas9 protein from Streptococcus pyogenes is the most investigated and highly used enzyme of its class. Nevertheless, it has some drawbacks, including a relatively big size, imperfect specificity and restriction to DNA targets flanked by an NGG PAM sequence. Cas9 orthologs from other bacterial species may provide a rich and largely untapped source of biochemical diversity, which can help to overcome the limitations of SpCas9. Here, we characterize CcCas9, a Type II-C CRISPR nuclease from Clostridium cellulolyticum H10. We show that CcCas9 is an active endonuclease of comparatively small size that recognizes a novel two-nucleotide PAM sequence. The CcCas9 can potentially broaden the existing scope of biotechnological applications of Cas9 nucleases and may be particularly advantageous for genome editing of C. cellulolyticum H10, a bacterium considered to be a promising biofuel producer.
Biplanar X-Ray Methods for Stereotactic Intraoperative Localization in Deep Brain Stimulation Surgery
Authors: Sedrak Mark , Sabelman Eric , Pezeshkian Patrick , Duncan John , Bernstein Ivan , Bruce Diana , Tse Victor , Khandhar Suketu , Call Elena , Heit Gary , Alaminos-Bouza Armando 
Published: December 2019

Abstract

BACKGROUND
Efficacy in deep brain stimulation (DBS) is dependent on precise positioning of electrodes within the brain. Intraoperative fluoroscopy, computed tomography (CT), or magnetic resonance imaging are used for stereotactic intraoperative localization (StIL), but the utility of biplanar X-ray has not been evaluated in detail.

OBJECTIVE
To determine if analysis of orthogonal biplanar X-rays using graphical analysis (GA), ray tracing (RT), and/or perspective projection (PP) can be utilized for StIL.

METHODS
A review of electrode tip positions comparing postoperative CT to X-ray methods was performed for DBS operations containing orthogonal biplanar X-ray with referential spheres and pins.

RESULTS
Euclidean (Re) errors for final DBS electrode position on intraoperative X-rays vs postoperative CT using GA, RT, and PP methods averaged 1.58 mm (±0.75), 0.74 mm (±0.45), and 1.07 mm (±0.64), respectively (n = 56). GA was more accurate with a ventriculogram. RT and PP predicted positions that correlated with third ventricular structures on ventriculogram cases. RT was the most stable but required knowledge of the geometric setup. PP was more flexible than RT but required well-distributed reference points. A single case using the O-arm demonstrated Re errors of 0.43 mm and 0.28 mm for RT and PP, respectively. In addition, these techniques could also be used to calculate directional electrode rotation.

CONCLUSION
GA, RT, and PP can be employed for precise StIL during DBS using orthogonal biplanar X-ray. These methods may be generalized to other stereotactic procedures or instances of biplanar imaging such as angiograms, radiosurgery, or injection therapeutics.
Shock Transmission Through Cross-Border Bank Lending: Credit and Real Effects
Authors: Hale Galina , Kapan Tümer , Minoiu Camelia 
Published: December 2019

Abstract
We study the transmission of financial shocks across borders through international bank connections. Using data on cross-border interbank loans among 6,000 banks during 1997–2012, we estimate the effect of asset-side exposures to banks in countries experiencing systemic banking crises on profitability, credit, and the performance of borrower firms. Crisis exposures reduce bank returns and tighten credit conditions for borrowers, constraining investment and growth. The effects are larger for foreign borrowers, including in countries not experiencing banking crises. Our results document the extent of cross-border crisis transmission, but also highlight the resilience of financial networks to idiosyncratic shocks.
Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus
Authors: Zaidi Faseeh , Narang Ravi K , Phipps-Green Amanda , Gamble Greg G , Tausche Anne-Katherin , So Alexander , Riches Philip , Andres Mariano , Perez-Ruiz Fernando , Doherty Michael , Janssen Matthijs , Joosten Leo A B , Jansen Tim L , Kurreeman Fina , Torres Rosa J , McCarthy Geraldine M , Miner Jeffrey N , Stamp Lisa K , Merriman Tony R , Dalbeth Nicola 
Published: December 2019

Abstract

Objective
The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout.

Methods
Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout &lt;40 years of age. Single nucleotide polymorphisms (SNPs) for the 10 loci most strongly associated with serum urate were genotyped. Allelic association of the SNPs with early-onset gout was tested using logistic regression in an unadjusted model and in a model adjusted for sex, body mass index, tophus presence, flare frequency, serum creatinine and highest serum urate. The analysis was also done in two replication cohorts: Eurogout (n = 704) and Ardea (n = 755), and data were meta-analysed.

Results
In the Genetics of Gout in Aotearoa study, there were 638 (42.4%) participants with early-onset gout. The ABCG2 rs2231142 gout risk T-allele was present more frequently in participants with early-onset gout compared with the later-onset group. For the other SNPs tested, no differences in risk allele number were observed. In the allelic association analysis, the ABCG2 rs2231142 T-allele was associated with early-onset gout in unadjusted and adjusted models. Analysis of the replication cohorts confirmed the association of early-onset gout with the ABCG2 rs2231142 T-allele, but not with other serum urate-associated SNPs. In the meta-analysis, the odds ratio (95% CI) for early-onset gout for the ABCG2 rs2231142 T-allele was 1.60 (1.41, 1.83).

Conclusion
In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout.
Surgical Management of Multiple Rib Fractures Reduces the Hospital Length of Stay and the Mortality Rate in Major Trauma Patients: A Comparative Study in a UK Major Trauma Center
Authors: Gerakopoulos Efstratios , Walker Leonie , Melling David , Scott Sharon , Scott Simon 
Published: December 2019

Objectives:
To investigate and assess the effectiveness of surgical fixation of rib fractures in complex traumatic chest injuries compared with traditional nonoperative management.

Design:
Retrospective observational comparative study.

Setting:
Level 1 Major Trauma Centre in North West England.

Patients/Participants:
A total of 83 patients who were admitted urgently to our hospital after major trauma, between August 2012 and March 2015, and fulfilled the criteria for surgical fixation of their multiple rib fractures. Patients who had concomitant nonsurvivable injuries or did not consent for surgery were excluded.

Intervention:
Open reduction and internal fixation (ORIF) of multiple rib fractures and flail chest segments versus traditional nonoperative management.

Main Outcome Measurements:
The primary outcome of interest was the total hospital length of stay (LOS). Secondary outcomes included the incidence of intensive care unit (ICU) admission and the incidence of respiratory complications such as hospital-acquired pneumonia, need for mechanical ventilation, and/or tracheotomy. The mortality rate was also investigated.

Results:
A total of 83 patients were included, 47 of these in the ORIF group and 36 in the non-ORIF group. The mean hospital LOS for patients in the non-ORIF group was 30.41 days (SD 30.1). This was markedly reduced in the ORIF group to a mean of 14.53 days (SD 11.7), with the difference being statistically significant (P < 0.01). Twenty-eight patients (77.7%) in the nonoperatively managed group required admission to the ICU compared with a significantly lower 48.9% (23 patients) in the ORIF group (P < 0.01). The incidence of respiratory complications was lower in the ORIF group but this difference was not statistically significant. The mortality rate was 2.1% for the group that was treated surgically compared with 13.9% for the conservative group (P < 0.05).

Conclusions:
Surgical fixation of multiple displaced rib fractures reduced the total hospital LOS and the overall mortality in our major trauma patients and decreased the incidence of ICU admission.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Management of Opioid and Sedative Weaning in Pediatric Congenital Heart Disease Patients
Authors: O’Connell Caitlin , Ziniel Sonja , Hartwell Lauren , Connor Jean 
Published: December 2019

Background:
Opioid and sedative medications are commonly used to treat pediatric patients with congenital heart disease; however, their use is not without adverse effects. Symptoms of withdrawal can occur if the medications are discontinued abruptly or weaned too quickly.

Objective:
The aim of this study was to understand and describe the current management of opioid and sedative weaning in pediatric congenital heart disease patients in freestanding children’s hospitals across the United States.

Methods:
A Web-based survey of pediatric congenital heart centers was conducted. Survey participants were recruited from the Consortium of Congenital Cardiac Care–Measurement of Nursing Practice. Quantitative data were summarized using frequency and proportions. Qualitative data were summarized using content analysis.

Results:
Twelve sites participated in the survey (44% response rate). Methadone was used as a weaning medication at 100% of participating sites, lorazepam at 83% of sites, and clonidine at 75% of sites. Seventy-five percent of sites reported using a clinical assessment tool to monitor withdrawal symptoms. Twenty-five percent of sites used a standardized clinical pathway when weaning opioid and sedative medications. Eighty-three percent of sites will consider discharging a patient to complete the medication wean at home.

Discussion:
Weaning practices varied across sites. While some similarities were observed among sites, substantial practice variation exists. The majority of sites used a clinical assessment tool to assess for withdrawal symptoms. Few sites reported using a standardized approach to weaning patients. Discharging patients to complete an opioid or sedative wean at home was common practice. Opportunities exist for the development of weaning practice guidelines.
Organizational Learning in a Cardiac Intensive Care Unit
Authors: Lyman Bret , Ethington Kalene M. , King Carly , Jacobs Jonathan D. , Lundeen Hayley 
Published: December 2019

Introduction:
Providing high-quality care to every patient is challenging, particularly in critical care units (CCUs). However, this standard can be achieved through organizational learning. Unfortunately, the process of organizational learning in CCUs is not well understood.

Objective:
The objective of this study is to describe the developmental progression of a cardiac intensive care unit (CICU) to reach its current state of reliably excellent clinical performance.

Methods:
The method selected for this study was a learning history. A total of 43 individuals with experience working on the CICU participated in small group interviews. Participants included nurses, surgeons, unit clerks, administrators, nursing assistants, a pharmacist, a respiratory therapist, and an administrative assistant. Relevant artifacts, including unit performance data, were also gathered to complement interview data.

Results:
The CICU progressed through 4 distinct developmental stages to reach its current state. The CICU’s early development involved establishing psychological safety on the unit, which prepared the unit for increased accountability, improved performance, and the pursuit of reliability.

Discussion/Conclusion:
The findings validate the relationship between psychological safety and organizational learning, offer insight into how CCUs become high-reliability organizations, and provide clinical leaders with guidance for achieving high reliability in their organizations. The findings also help validate the American Association of Critical-Care Nurses position that a healthy work environment is essential to achieving clinical excellence. Critical care unit teams should use these findings as a framework for collective reflection and planning to achieve their desired future. Further research is needed to validate the applicability of these findings and to continue building the evidence base for organizational learning in hospital units.
Critical Care Nurses' Perceptions of End-of-Life Care Obstacles
Authors: Beckstrand Renea L. , Lamoreaux Nicole , Luthy Karlen E. , Macintosh Janelle L.B. 
Published: December 2019

Background:
Nurses working in intensive care units (ICUs) frequently care for patients and their families at the end of life (EOL). Providing high-quality EOL care is important for both patients and families, yet ICU nurses face many obstacles that hinder EOL care. Researchers have identified various ICU nurse-perceived obstacles, but no studies have been found addressing the progress that has been made for the last 17 years.

Objective:
The aims of this study were to determine the most common and current obstacles in EOL care as perceived by ICU nurses and then to evaluate whether meaningful changes have occurred since data were first gathered in 1998.

Methods:
A quantitative-qualitative mixed methods design was used. A random, geographically dispersed sample of 2000 members of the American Association of Critical-Care Nurses was surveyed.

Results:
Five obstacle items increased in mean score and rank as compared with 1999 data including (1) family not understanding what the phrase “lifesaving measures” really means, (2) providing lifesaving measures at families' requests despite patient's advance directive listing no such care, (3) family not accepting patient's poor prognosis, (4) family members fighting about the use of life support, and (5) not enough time to provide EOL care because the nurse is consumed with lifesaving measures attempting to save the patient's life. Five obstacle items decreased in mean score and rank compared with 1999 data including (1) physicians differing in opinion about care of the patient, (2) family and friends who continually call the nurse rather than calling the designated family member, (3) physicians who are evasive and avoid families, (4) nurses having to deal with angry families, and (5) nurses not knowing their patient's wishes regarding continuing with tests and treatments.

Conclusions:
Obstacles in EOL care, as perceived by critical care nurses, still exist. Family-related obstacles have increased over time. Obstacles related to families may not be easily overcome as each family, dealing with a dying family member in an ICU, likely has not previously experienced a similar situation. On the basis of the current top 5 obstacles, recommendations for possible areas of focus include (1) improved health literacy assessment of families followed by earlier directed, appropriate, and specific EOL information; (2) improved physician/team communication; and (3) ensuring patients' wishes are followed as written. In general, patient- and family-centered care using clear and open EOL communication regarding wishes and desires between patients and families, their physicians, and nurses will help decrease common obstacles, thus improving the quality of EOL care provided to dying patients and families.