bluuebunny/crossref_metadata_2025_split huggingface dataset:
A network-based conditional genetic association analysis of the human metabolome
Authors: Tsepilov Y A , Sharapov S Z , Zaytseva O O , Krumsek J , Prehn C , Adamski J , Kastenmüller G , Wang-Sattler R , Strauch K , Gieger C , Aulchenko Y S 
Published: November 2018

Abstract

Background
Genome-wide association studies have identified hundreds of loci that influence a wide variety of complex human traits; however, little is known regarding the biological mechanism of action of these loci. The recent accumulation of functional genomics (“omics”), including metabolomics data, has created new opportunities for studying the functional role of specific changes in the genome. Functional genomic data are characterized by their high dimensionality, the presence of (strong) statistical dependency between traits, and, potentially, complex genetic control. Therefore, the analysis of such data requires specific statistical genetics methods.

Results
To facilitate our understanding of the genetic control of omics phenotypes, we propose a trait-centered, network-based conditional genetic association (cGAS) approach for identifying the direct effects of genetic variants on omics-based traits. For each trait of interest, we selected from a biological network a set of other traits to be used as covariates in the cGAS. The network can be reconstructed either from biological pathway databases (a mechanistic approach) or directly from the data, using a Gaussian graphical model applied to the metabolome (a data-driven approach). We derived mathematical expressions that allow comparison of the power of univariate analyses with conditional genetic association analyses. We then tested our approach using data from a population-based Cooperative Health Research in the region of Augsburg (KORA) study (n = 1,784 subjects, 1.7 million single-nucleotide polymorphisms) with measured data for 151 metabolites.

Conclusions
We found that compared to single-trait analysis, performing a genetic association analysis that includes biologically relevant covariates can either gain or lose power, depending on specific pleiotropic scenarios, for which we provide empirical examples. In the context of analyzed metabolomics data, the mechanistic network approach had more power compared to the data-driven approach. Nevertheless, we believe that our analysis shows that neither a prior-knowledge-only approach nor a phenotypic-data-only approach is optimal, and we discuss possibilities for improvement.
Development of a fully automated PCR assay for the detection of Pneumocystis jirovecii using the GENECUBE system
Authors: Matsumura Yasufumi , Tsuchido Yasuhiro , Yamamoto Masaki , Nakano Satoshi , Nagao Miki 
Published: November 2018

AbstractWe developed a fully automated polymerase chain reaction (PCR) assay for the detection of Pneumocystis jirovecii using the GENECUBE system. This assay was evaluated against an in-house real-time PCR assay using 82 bronchoalveolar lavage and 139 sputum samples from 221 immunocompromised patients who were suspected of having Pneumocystis pneumonia (PCP). After loading the maximum of eight samples into the GENECUBE system, the results were obtained within approximately 60 minutes. The overall positivity rate of both assays was 35%, and the concordance rate was 89% (kappa, 0.76). Based on the clinical diagnosis of 39 PCP and 105 non-PCP patients, the GENECUBE and real-time assays had sensitivities of 92.3% and 94.9% and specificities of 85.7% and 85.7%, respectively. This automated and rapid assay is a promising tool for the detection of P. jirovecii in routine clinical laboratory practice.
Convergent Evidence That ZNF804A Is a Regulator of Pre-messenger RNA Processing and Gene Expression
Authors: Chapman Ria M , Tinsley Caroline L , Hill Matthew J , Forrest Marc P , Tansey Katherine E , Pardiñas Antonio F , Rees Elliott , Doyle A Michelle , Wilkinson Lawrence S , Owen Michael J , O’Donovan Michael C , Blake Derek J 
Published: November 2018

Abstract
Genome-wide association studies have linked common variation in ZNF804A with an increased risk of schizophrenia. However, little is known about the biology of ZNF804A and its role in schizophrenia. Here, we investigate the function of ZNF804A using a variety of complementary molecular techniques. We show that ZNF804A is a nuclear protein that interacts with neuronal RNA splicing factors and RNA-binding proteins including RBFOX1, which is also associated with schizophrenia, CELF3/4, components of the ubiquitin-proteasome system and the ZNF804A paralog, GPATCH8. GPATCH8 also interacts with splicing factors and is localized to nuclear speckles indicative of a role in pre-messenger RNA (mRNA) processing. Sequence analysis showed that GPATCH8 contains ultraconserved, alternatively spliced poison exons that are also regulated by RBFOX proteins. ZNF804A knockdown in SH-SY5Y cells resulted in robust changes in gene expression and pre-mRNA splicing converging on pathways associated with nervous system development, synaptic contact, and cell adhesion. We observed enrichment (P = 1.66 × 10–9) for differentially spliced genes in ZNF804A-depleted cells among genes that contain RBFOX-dependent alternatively spliced exons. Differentially spliced genes in ZNF804A-depleted cells were also enriched for genes harboring de novo loss of function mutations in autism spectrum disorder (P = 6.25 × 10–7, enrichment 2.16) and common variant alleles associated with schizophrenia (P = .014), bipolar disorder and schizophrenia (P = .003), and autism spectrum disorder (P = .005). These data suggest that ZNF804A and its paralogs may interact with neuronal-splicing factors and RNA-binding proteins to regulate the expression of a subset of synaptic and neurodevelopmental genes.
Understanding the role of advanced practice providers in oncology in the United States
Authors: Bruinooge Suanna S. , Pickard Todd A. , Vogel Wendy , Hanley Amy , Schenkel Caroline , Garrett-Mayer Elizabeth , Tetzlaff Eric , Rosenzweig Margaret , Hylton Heather , Westin Shannon N. , Smith Noël , Lynch Conor , Kosty Michael P. , Williams Stephanie F. 
Published: November 2018

ABSTRACT

Purpose:
Advanced practice providers (APPs, which include NPs and physician assistants [PAs]) are integral members of oncology teams. This study aims first to identify all APPs in oncology and, second, to understand personal and practice characteristics (including compensation) of those APPs.

Methods:
We identified APPs who practice oncology from membership and claims data. We surveyed 3,055 APPs about their roles in clinical care.

Results:
We identified at least 5,350 APPs in oncology and an additional 5,400 who might practice oncology. Survey respondents totaled 577 out of 3,055, which provided a 19% response rate. Results focused on 540 NPs and PAs. Greater than 90% reported satisfaction with career choice. Respondents identified predominately as white (89%) and female (94%). NPs and PAs spent the majority (80%) of time in direct patient care. The top four patient care activities were patient counseling (NPs, 94%; PAs, 98%), prescribing (NPs, 93%; PAs, 97%), treatment management (NPs, 89%; PAs, 93%), and follow-up visits (NPs, 81%; PAs, 86%). A majority of all APPs reported both independent and shared visits (65% hematology/oncology/survivorship/prevention/pediatric hematology/oncology; 85% surgical/gynecologic oncology; 78% radiation oncology). A minority of APPs reported that they conducted only shared visits. Average annual compensation was between $113,000 and $115,000, which is about $10,000 higher than average pay for APPs not in oncology.

Conclusion:
We identified 5,350 APPs in oncology and conclude that number may be as high as 7,000. Survey results suggest that practices that incorporate APPs routinely rely on them for patient care. Given the increasing number of patients with and survivors of cancer, APPs are important to ensure access to quality cancer care now and in the future.
Reflections on a Decade Leading a Medical Student Well-Being Initiative
Authors: Slavin Stuart 
Published: November 2018

One of the earliest longitudinal efforts to improve medical student well-being, and perhaps the only one that has tracked mental health outcomes continuously, is the decade-long medical student well-being initiative at Saint Louis University School of Medicine. In this Invited Commentary, the author describes his experience leading that effort as the associate dean for curriculum to help inform more nascent efforts taking shape across the medical education continuum and in practice.
Starting in 2006, a simple model with three components was developed to guide the new well-being initiative: (1) Reduce unnecessary stressors and enhance the learning environment; (2) teach students skills to better manage their stress and provide and encourage them to use a range of psychological and emotional support resources; and (3) create more opportunities for students to find meaning in their work. Over the next 10 years, striking decreases in adverse mental health outcomes were seen with an 85% reduction in the depression rate and a 75% decrease in the anxiety rate in first-year medical students.
The author argues that the following factors contributed to the initiative’s effectiveness: addressing the problem largely as one stemming from the learning environment, developing a deep understanding of the lived experience of students and avoiding making assumptions about what they need, reducing students’ cognitive load, addressing problematic student mind-sets through a modest resilience curriculum, treating students with respect and compassion, and creating greater opportunity for students to find meaning in their work.
Derotational Pronation-producing Osteotomy of the Radius and Biceps Tendon Rerouting for Supination Contractures in Neonatal Brachial Plexus Palsy Patients: A Review of 20 Cases
Authors: DeDeugd Casey M. , Shin Alexander Y. , Shaughnessy William J. 
Published: November 2018

Background:
Forearm supination contractures can occur as a result of neurological derangement of the upper extremity in patients with neonatal brachial plexus birth palsy. The contractures become problematic in childhood as patients begin requiring forearm pronation for activities of daily living including typing on a keyboard and writing. There have been several techniques described to remedy this deformity. We present a case series describing the early clinical results of combined radial osteotomy and intraosseous biceps rerouting to realign the forearm in resting pronation and convert the biceps from a supinator to a pronator.

Methods:
A retrospective review identified patients who had a radial osteotomy and biceps rerouting for supination contracture between 2006 and 2016. Inclusion criteria required a fixed forearm supination contracture, patients below 18 years of age and at least 1 year of clinical and radiographic follow-up. Demographic and surgical variables, early clinical results, complications, reoperations, and revisions were documented.

Results:
Twenty patients were identified who met inclusion criteria. The mean follow-up was 3 years (range, 1 to 9 y). We observed a statistically significant difference in the mean resting position of the forearm from 56 degrees of supination preoperatively to 17 degrees of pronation postoperatively. Correspondingly, there was an increase in passive forearm pronation from 0 degree preoperatively to 66 degrees postoperatively and an expected decrease in passive forearm supination from 78 degrees preoperatively to 41 degrees postoperatively. There were 2 complications which were both radial osteotomy nonunions. Excluding revisions, there were 14 reoperations in 14 patients (63%) for hardware removal. Hardware removal was considered an expected return to the operating room, not an unplanned reoperation. There were 2 revisions for osteotomy nonunion, both of which went on to eventual union. Overall survivorship from the need for revision surgery was 95% at 12 months, 88% at 24 months, and 88% at 60 months. There were no recurrences of the supination contracture.

Conclusions:
We present results of a novel surgical solution to forearm supination contractures through the combination of a derotational osteotomy of the radius and biceps tendon rerouting. The results show a significant benefit in forearm positioning and passive pronation with excellent survivorship and maintenance of correction.

Level of Evidence:
Level IV—therapeutic.
Prescription Drug Monitoring Programs and Opioid Overdoses
Authors: Castillo-Carniglia Alvaro , Ponicki William R. , Gaidus Andrew , Gruenewald Paul J. , Marshall Brandon D. L. , Fink David S. , Martins Silvia S. , Rivera-Aguirre Ariadne , Wintemute Garen J. , Cerdá Magdalena 
Published: November 2018

Background:
Prescription drug monitoring program are designed to reduce harms from prescription opioids; however, little is known about what populations benefit the most from these programs. We investigated how the relation between implementation of online prescription drug monitoring programs and rates of hospitalizations related to prescription opioids and heroin overdose changed over time, and varied across county levels of poverty and unemployment, and levels of medical access to opioids.

Methods:
Ecologic county-level, spatiotemporal study, including 990 counties within 16 states, in 2001–2014. We modeled overdose counts using Bayesian hierarchical Poisson models. We defined medical access to opioids as the county-level rate of hospital discharges for noncancer pain conditions.

Results:
In 2010–2014, online prescription drug monitoring programs were associated with lower rates of prescription opioid-related hospitalizations (rate ratio 2014 = 0.74; 95% credible interval = 0.69, 0.80). The association between online prescription drug monitoring programs and heroin-related hospitalization was also negative but tended to increase in later years. Counties with lower rates of noncancer pain conditions experienced a lower decrease in prescription opioid overdose and a faster increase in heroin overdoses. No differences were observed across different county levels of poverty and unemployment.

Conclusions:
Areas with lower levels of noncancer pain conditions experienced the smallest decrease in prescription opioid overdose and the faster increase in heroin overdose following implementation of online prescription drug monitoring programs. Our results are consistent with the hypothesis that prescription drug monitoring programs are most effective in areas where people are likely to access opioids through medical providers.
Psychosocial Adversity in Infancy and Mortality Rates in Childhood and Adolescence
Authors: Østergaard Søren Dinesen , Larsen Janne Tidselbak , Petersen Liselotte , Smith George Davey , Agerbo Esben 
Published: November 2018

Background:
Childhood and adolescent mortality accounts for a substantial proportion of years lost prematurely. Reducing childhood and adolescent mortality relies on knowing characteristics of those at elevated risk of dying young. We therefore aimed to identify such characteristics; our main hypothesis is that psychosocial adversity in infancy is linked to increased mortality rates in childhood and adolescence.

Methods:
We conducted a register-based cohort study involving all 1,549,581 children born to Danish-born parents in Denmark between 1 January 1981 and 31 December 2010. For each infant, we extracted data relevant to Rutter’s indicators of adversity (low social class, parents not cohabiting, large family size, paternal criminality, maternal mental disorder, and placement in out-of-home care). Follow-up began on the cohort member’s first birthday. We estimated the association between adversity score (the number of Rutter’s indicators of adversity present in infancy) and death via. Cox regression.

Results:
During follow-up (18,874,589 person-years), 2,081 boys and 1,420 girls died before or on their 18th birthday. The hazard ratios for death were 2.3 (95% CI = 1.9, 2.9) and 2.1 (95% CI = 1.6, 2.7) for boys and girls with adversity scores of 3–6 compared with those with a score of 0. These associations were driven by causes of death with known links to psychosocial adversity.

Conclusion:
While absolute mortality rates were low, infants with adversity scores of 3–6 were approximately twice as likely to die prematurely compared with infants with adversity scores of 0. Whether these associations generalize to other countries should be subjected to further study.
Calibration and Statistical Performance of Al2O3:C Optically Stimulated Luminescent Dosimeters With and Without Annealing Using a 137Cs Source
Authors: Liu Kevin , Golduber Robert M. , Trimas David J. , Abraham Sara A. , Latosz Logan V. , Mapes Jasmine L. , Miller Jonathan M. , Kearfott Kimberlee J. 
Published: November 2018

Abstract
A series of experiments were conducted using commercially available Al2O3:C optically stimulated luminescent dosimeters to provide a technical basis for their precise calibration and statistical performance at irradiated air kerma doses between 0.02 mGy and 5 mGy using 137Cs. This study examines the dose response linearity, studies the background signal for annealed dosimeters, and compares the statistical performance of dosimeters that were annealed and not annealed prior to their irradiation and readout. The average and standard deviation for the response of groups of dosimeters annealed and nonannealed prior to their irradiation were determined at each delivered dose. The batch of dosimeters that were annealed prior to their irradiation exhibited a coefficient of variation in its mean dose response below 10% when using three or more irradiation trials at each delivered air kerma dose between 0.02 mGy and 5 mGy. The reader calibration factor was calculated using the response of the annealed batch of dosimeters and was determined to be 756 ± 7 photomultiplier tube counts per mGy. Best estimates of the individual sensitivity factors were determined to be between 0.79 and 1.12 for the annealed batch of dosimeters. The minimum number of irradiations required to accurately determine the sensitivity factor of each individual dosimeter is reported with the recommended reader and dosimeter calibration procedures.
Synopsis of the Oak Ridge Radiation Protection Research Needs Workshop
Authors: Davis Jason , Dewji Shaheen Azim , Abelquist Eric , Hertel Nolan 
Published: November 2018

Abstract
Radiation protection is foundational to harnessing the societal benefits of radiation in nuclear energy, security, and medicine applications. Significant challenges in radiation protection remain unaddressed for the nuclear fuel cycle, nuclear medicine, emergency response, national defense, and space exploration, as the United States is lacking a coherent research strategy prioritizing radiation protection mission needs and gaps in scientific knowledge to meet these needs. Research and development in the field of radiation protection calls for cooperation among governmental agencies, emergency responders, research organizations, and the academic community. Amidst atrophying national expertise in radiation protection, the Radiation Protection Research Needs Workshop was spearheaded by the Oak Ridge Associated Universities, Oak Ridge National Laboratory, and the Health Physics Society. This workshop facilitated critical dialogue among radiation stakeholders in the governmental and scientific communities, including national laboratories, academic institutions, and industry partners. The workshop featured presentations representing 12 federal agencies and breakout sessions involving the identification of scientific drivers by subject matter experts in each of the following areas: new fuel cycles/reactors, dosimetry, medical physics, instrumentation and operations, decontamination and decommissioning, space radiation, national defense, emergency response, environmental modeling, and low-dose effects. The goal of this workshop was to seek stakeholder input toward the development of a national strategic research agenda in the field of radiation protection. Consequently, the Health Physics Society has established a Special Task Force on Health Physics Research Needs, tasked with the prioritization of scientific drivers in radiation protection for the development of a national strategic research agenda.
Quality Appraisal of Systematic Reviews for Behavioral Treatments of Attention Disorders in Traumatic Brain Injury
Authors: Roitsch Jane , Redman Rachael , Michalek Anne M. P. , Johnson Rachel K. , Raymer Anastasia M. 
Published: November 2018

Objective:
This review appraised the quality of systematic reviews (SRs) and meta-analyses (MAs) to summarize research on behavioral interventions for attention disorders in persons with traumatic brain injury.

Methods:
A search of 7 databases revealed 15 MAs/SRs reporting outcomes for attention treatments in traumatic brain injury. Two examiners independently coded the quality of reviews with the Critical Appraisal of Systematic Review or Meta-Analysis and the Evidence in Augmentative and Alternative Communication Systematic Review Scale.

Results:
The findings of both scales were highly correlated. Four reviews were conducted with high methodologic rigor indicated by a score of 60% or greater on both scales. No other study scored above 45%. Among the well-conducted SRs/MAs, evidence for direct attention training effects was limited to basic attention exercises, with little generalization to functional activities. Strategy training for activities and tasks requiring attentional abilities had a stronger evidence base in 1 rigorous MA.

Conclusions:
This appraisal provides valuable practice information. The conclusions of 4 rigorous reviews suggest that there is only limited positive scientific support for the effects of attention treatments for traumatic brain injury. Future SRs/MAs would benefit from adherence to review guidelines.
A Systematic Review of Sleep-Wake Disturbances in Childhood Traumatic Brain Injury: Relationship with Fatigue, Depression, and Quality of Life
Authors: Botchway Edith N. , Godfrey Celia , Anderson Vicki , Catroppa Cathy 
Published: November 2018

Objective:
To systematically appraise the literature on the prevalence, types, and predictors of sleep-wake disturbances (SWD), and on the relationship between SWD, fatigue, depression, and quality of life in children and adolescents with traumatic brain injury (TBI).

Methods:
MEDLINE, PubMed, PsychInfo, Web of Science, and EMBASE databases were searched, reference lists of retrieved articles were also searched for relevant articles, and study methods were evaluated for risk of bias.

Results:
Of the 620 articles assessed, 16 met inclusion criteria. Sleep-wake disturbances were common in childhood TBI. The most common types of SWD reported were insomnia and excessive daytime sleepiness, with mild TBI participants showing a trend toward more sleep maintenance insomnia, while sleep-onset insomnia was typical in those with moderate-severe TBI. Predictors of SWD reported in studies involving mild TBI participants included TBI severity, male sex, preexisting SWD, high body weight, and depression; while injury severity and internalizing problems were associated with SWD in moderate-severe TBI participants. Sleep-wake disturbances were also associated with fatigue and poor quality of life following TBI.

Conclusion:
Sleep-wake disturbances are highly prevalent in childhood TBI, regardless of injury severity. Routine assessments of SWD in survivors of childhood TBI are recommended.