bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loci specific epigenetic drug sensitivity
Authors: Zhang Thanutra , Pilko Anna , Wollman Roy 
Published: March 2020

Abstract
Therapeutic targeting of epigenetic modulators offers a novel approach to the treatment of multiple diseases. The cellular consequences of chemical compounds that target epigenetic regulators (epi-drugs) are complex. Epi-drugs affect global cellular phenotypes and cause local changes to gene expression due to alteration of a gene chromatin environment. Despite increasing use in the clinic, the mechanisms responsible for cellular changes are unclear. Specifically, to what degree the effects are a result of cell-wide changes or disease related locus specific effects is unknown. Here we developed a platform to systematically and simultaneously investigate the sensitivity of epi-drugs at hundreds of genomic locations by combining DNA barcoding, unique split-pool encoding, and single cell expression measurements. Internal controls are used to isolate locus specific effects separately from any global consequences these drugs have. Using this platform we discovered wide-spread loci specific sensitivities to epi-drugs for three distinct epi-drugs that target histone deacetylase, DNA methylation and bromodomain proteins. By leveraging ENCODE data on chromatin modification, we identified features of chromatin environments that are most likely to be affected by epi-drugs. The measurements of loci specific epi-drugs sensitivities will pave the way to the development of targeted therapy for personalized medicine.
Highlights of the 2019 Society for Neuro-Oncology Inaugural Brain Metastases Conference: establishing a dedicated meeting to address an unmet need in the field
Authors: Zuccato Jeffrey A , Aizer Ayal A , Lee Eudocia Quant , Ahluwalia Manmeet S , O’Halloran Philip J , Mansouri Alireza , Wen Patrick Y , Zadeh Gelareh 
Published: March 2020

Abstract
Brain metastases comprise the majority of central nervous tumors in adults and confer poorer survival for patients with primary cancer. Systemic disease control is improving with advances in treatment for primary tumors and the complexity of brain metastases management is increasing with multimodality approaches incorporating combinations of surgery, radiotherapy, chemotherapy, targeted therapies, and immunotherapy. Accordingly, the Society for Neuro-Oncology established an annual brain metastases conference to unite colleagues from multiple disciplines with content spanning a range of timely topics relevant to improving our understanding of brain metastases and how they are optimally treated. The inaugural meeting on August 16–17, 2019 was very successful with 163 impactful presentations being delivered to a large multidisciplinary audience on current research advances in the field of neuro-oncology. This review summarizes the major themes of the meeting and highlights the main findings presented.
Interferon-β exposure induces a fragile glioblastoma stem cell phenotype with a transcriptional profile of reduced migratory and MAPK pathway activity
Authors: Lohmann Birthe , Silginer Manuela , Picard Daniel , Schneider Hannah , Remke Marc , Roth Patrick , Reifenberger Guido , Weller Michael 
Published: March 2020

AbstractBackgroundType I interferons (IFN-α/β) are cytokines that are typically expressed in response to double-stranded RNA associated with viral infections. Glioblastomas are the most common malignant primary brain tumors, characterized by an infiltrative growth pattern and prominent angiogenic activity, and thought to be maintained by a subpopulation of glioma-initiating (stem-like) cells (GICs). The growth of human GIC lines is highly sensitive to IFN-β.MethodsRepetitive pulse stimulation with IFN-β1a (IS) was used to generate IS sublines that had acquired resistance to IFN-β-induced suppression of sphere formation. These cell lines were characterized by analyses of type 1 IFN signaling, growth patterns, and transcriptomic profiles.ResultsHere we report that repetitive IFN-β1a stimulation (IS) induces a stable phenotype (referred to as IS) at the level of maintaining sphere formation, although classical IFN signaling defined by the expression of both IFN receptors, myxovirus resistance protein A (MxA) accumulation, and STAT1 induction is unaffected. Furthermore, this stably altered IS phenotype is characterized by constitutively decreased sphere formation capacity and morphological features of senescence and autophagy. Transcriptional profiling reveals increased type I IFN signaling in these IS cells, but decreased expression of genes involved in receptor signaling and cell migration.ConclusionsAltogether, these data suggest a role for promoting IFN-β signaling in glioblastoma and might provide clues to design future therapeutic approaches.
High Carriage Rates of Multidrug-Resistant Gram-Negative Bacteria in Neonatal Intensive Care Units From Ghana
Authors: Labi Appiah-Korang , Bjerrum Stephanie , Enweronu-Laryea Christabel C , Ayibor Prosper K , Nielsen Karen L , Marvig Rasmus L , Newman Mercy J , Andersen Leif P , Kurtzhals Jorgen A L 
Published: March 2020

Abstract

Background
Carriage of multidrug resistant (MDR) Gram-negative bacteria (GN) in hospitalized neonates may increase the risk of difficult-to-treat invasive infections at neonatal intensive care units (NICUs). Data on MDRGN carriage among hospitalized newborns in Africa are limited.

Methods
We conducted a cross-sectional study at the NICUs of 2 tertiary hospitals in Ghana. Swabs from the axilla, groin, perianal region, and the environment were cultured, GN were identified, and antibiotic susceptibility was tested. We obtained blood culture isolates from neonates with sepsis. Whole-genome sequencing was used to characterize carbapenemase-producing Klebsiella pneumoniae. Typing was done by multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis.

Results
A total of 276 GN were isolated from 228 screened neonates. Pathogenic GN were cultured in 76.8% (175 of 228) of neonates. Klebsiella spp (41.7%; 115 of 276) and Escherichia coli (26.4%; 73 of 276) were the commonest organisms. Carriage rates of MDRGN and third-generation cephalosporin resistant organisms were 49.6% (113 of 228) and 46.1% (105 of 228), respectively. Among Klebsiella spp, 75.6% (87 of 115) phenotypically expressed extended-spectrum β-lactamase activity, whereas 15.6% expressed carbapenemase and harbored bla-OXA-181 and bla-CTX-M-15. Overall, 7.0% (16 of 228) of neonates developed GN bloodstream infection. In 2 of 11 neonates, sequencing showed the same identity between carriage and the bloodstream isolate. Length of stay before specimen collection and antibiotic use were independently associated with carriage rates, which increased from 13% at admission to 42% by day 2 and reached a plateau at 91% by day 15.

Conclusions
High carriage rates of MDRGN, including carbapenemase-producing enterobacterales may be an emerging problem in NICUs in Africa.
Risk Factors for Positive Follow-Up Blood Cultures in Gram-Negative Bacilli Bacteremia: Implications for Selecting Who Needs Follow-Up Blood Cultures
Authors: Mitaka Hayato , Gomez Tessa , Lee Young Im , Perlman David C 
Published: March 2020

Abstract

Background
The value of follow-up blood cultures (FUBCs) to document clearance of bacteremia due to Gram-negative bacilli (GNB) has not been well established. Although previous studies suggested that the yield of FUBCs for GNB bacteremia is low, it remains to be elucidated for whom FUBC may be beneficial and for whom it is unnecessary.

Methods
A retrospective cohort study was performed at 4 acute care hospitals to identify risk factors for positive FUBCs with GNB bacteremia and to better guide clinicians’ decisions as to which patients may or may not benefit from FUBCs. Participants included adult patients with GNB bacteremia who had FUBCs and were admitted between January 2017 and December 2018. The primary outcomes were the factors associated with positive FUBCs and the yield of FUBCs with and without the factors.

Results
Of 306 patients with GNB bacteremia who had FUBCs, 9.2% (95% confidence interval, 6.2%–13.0%) had the same GNB in FUBCs. In the multivariate logistic regression analysis, end-stage renal disease on hemodialysis, intravascular device, and bacteremia due to extended-spectrum β-lactamase or carbapenemase-producing organism were identified as independent predictors of positive FUBCs with GNB bacteremia. Approximately 7 FUBCs and 30 FUBCs were needed for patients with ≥1 or no risk factors, respectively, to yield 1 positive result.
SummaryThis multi-site retrospective cohort study found that among patients with gram-negative bacilli (GNB) bacteremia, having ESRD on hemodialysis, intravascular devices, or bacteremia due to multi-drug resistant GNB were each independently associated with having a positive follow-up blood culture.

Conclusions
Follow-up blood culture may not be necessary for all patients with GNB bacteremia and has the highest yield in patients with 1 or more risk factors.
Institutional ownership and governance
Authors: Franks Julian 
Published: March 2020

AbstractThis paper describes different forms of ownership across countries and how these forms influence the way companies are governed. In most stock markets in the world, listed companies frequently have a controlling shareholder, usually a family. However, Japan, the UK, and to a lesser extent the US, are exceptions. In these three countries, ownership is frequently highly fragmented, where share stakes are held by different institutional owners, including asset managers, both active and passive, and by shareholder activists. The paper focuses in particular on the governance structure of different institutional shareholders, how they engage with target firms, and their effectiveness. The paper concludes with recommendations for regulators to enhance different forms of ownership.
The Ottoman Postmaster: Contractors, Communication and Early Modern State Formation*
Authors: Koh Choon Hwee 
Published: March 2020

Abstract
Prevailing historiography views the use of contractors by states as indicative of a loss or decentralization of power. This article takes the case of the Ottoman postmaster to demonstrate how contracting could in fact strengthen early modern empires and to argue that the binary spatial metaphors of ‘centralization’ and ‘decentralization’ cannot adequately explain how power worked in the early modern world (about 1500–1800). Indeed, recent scholarship has highlighted the scale and significance of military contractors in early modern European warfare. However, contractors were not confined to expanding military capacity; they were also employed to expand administrative capacity in diverse arenas. Evidence from Ottoman fiscal documents and judicial registers shows how contracted postmasters played a crucial role in strengthening the imperial bureaucracy’s supervision of a sprawling postal system. In contrast to war-making, which involved the short-term mobilization of vast resources, maintaining a large-scale infrastructure required long-term co-ordination across multiple dispersed nodes, and this entailed a different spatial configuration of power that disrupts the dichotomous paradigm of centralization and decentralization. Ultimately, a holistic appraisal of early modern state-building needs to consider not just cases of war-making or provincial administration, but also pan-imperial infrastructures like information and communication systems.
Nationally Representative Health Care Expenditures of Community-Based Older Adults with Pain in the United States Prescribed Opioids vs Those Not Prescribed Opioids
Authors: Axon David R , Slack Marion , Barraza Leila , Lee Jeannie K , Warholak Terri 
Published: March 2020

Abstract

Objective
To compare health care expenditures between older US adults (≥50 years) with pain who were prescribed opioid medications and those who were not.

Design
Cross-sectional.

Setting
Community-based adults in the 2015 Medical Expenditure Panel Survey (MEPS).

Subjects
Nationally representative sample of US adults alive for the calendar year, aged 50 years or older, who reported having pain in the past four weeks.

Methods
Older US adults (≥50 years) with pain in the 2015 MEPS data were identified. The key independent variable was opioid prescription status (prescribed opioid vs not prescribed opioid). Hierarchical linear regression models assessed health care expenditures (inpatient, outpatient, office-based, emergency room, prescription medications, other, and total) in US dollars for opioid prescription status from a community-dwelling US population perspective, adjusting for covariates.

Results
The 2015 study cohort provided a national estimate of 50,898,592 noninstitutionalized US adults aged ≥50 years with pain in the past four weeks (prescribed opioid N = 16,757,516 [32.9%], not prescribed opioid N = 34,141,076 [67.1%]). After adjusting for covariates, individuals prescribed an opioid had 61% greater outpatient (β = 0.477, P &lt; 0.0001), 69% greater office-based (β = 0.524, P &lt; 0.0001), 14% greater emergency room (β = 0.131, P = 0.0045), 63% greater prescription medication (β = 0.486, P &lt; 0.0001), 29% greater other (β = 0.251, P = 0.0002), and 105% greater total (β = 0.718, P &lt; 0.0001) health care expenditures. There was no difference in opioid prescription status for inpatient expenditures (P &gt; 0.05).

Conclusions
This study raises awareness of the economic impact associated with opioid use among US older adults with pain. Future research should investigate these variables in greater depth, over longer time periods, and in additional populations.
Exploring Physical Therapist Adherence to Clinical Guidelines When Treating Patients With Knee Osteoarthritis in Australia: A Mixed Methods Study
Authors: Tang Clarice Y , Pile Rebecca , Croft Anna , Watson Narelle J 
Published: March 2020

Abstract

Objective
The authors aimed to understand how physical therapists used practice guidelines to manage patients with knee osteoarthritis (OA) in Australia.

Methods
This study used a concurrent triangulation mixed-method approach to explore how physical therapists applied clinical guidelines when managing patients with knee OA in an outpatient setting via completion of a semi-structured interview. Interviews were thematically analyzed by 2 investigators using an inductive approach. Themes were then triangulated to the results of an audit that evaluated the level of adherence to respective areas in the clinical guidelines among physical therapists at the participating site.

Results
One main theme and 3 subthemes were identified from 18 participants: (1) physical therapists were most confident in applying guidelines to improving range of movement and strength; (2) lack of knowledge in prescription of aerobic exercise, weight, and pain management; (3) pain is a bigger barrier in areas where knowledge is lacking; and (4) lack of clarity around the scope of practice. Themes converged with the reported level of adherence to guidelines.

Conclusions
Physical therapists commonly include range of movement and muscle strength exercises when managing people with knee OA. However, they were less confident in prescribing aerobic exercise and recommending weight and pain management strategies.

Impact
Apart from the need to upskill physical therapists in the aforementioned areas of clinical practice, the role of a physical therapist in the management of people with knee OA requires further clarification.
Decentralized Mining in Centralized Pools
Authors: Cong Lin William , He Zhiguo , Li Jiasun 
Published: March 2020

AbstractThe rise of centralized mining pools for risk sharing does not necessarily undermine the decentralization required for blockchains: because of miners’ cross-pool diversification and pool managers’ endogenous fee setting, larger pools better internalize their externality on global hash rates, charge higher fees, attract disproportionately fewer miners, and grow more slowly. Instead, mining pools as a financial innovation escalate miners’ arms race and significantly increase the energy consumption of proof-of-work-based blockchains. Empirical evidence from Bitcoin mining supports our model’s predictions. The economic insights inform other consensus protocols and the industrial organization of mainstream sectors with similar characteristics but ambiguous prior findings.
Predictors of implementation in the Faith, Activity, and Nutrition dissemination and implementation study: application of the Consolidated Framework for Implementation Research (CFIR) in a statewide initiative
Authors: Wilcox Sara , Jake-Schoffman Danielle E , Saunders Ruth P , Kinnard Deborah , Kaczynski Andrew T , Hutto Brent , James Katherine L 
Published: March 2020

Abstract
Faith-based organizations, with broad reach and trust, are well-positioned to promote health. The purpose of the study was to examine 12-month implementation and its predictors in the statewide Faith, Activity, and Nutrition (FAN) dissemination and implementation (D&I) study. Churches (n = 93; 42% predominantly African American) in the [South Carolina] Conference of the United Methodist Church trained by Community Health Advisors participated in the study. Church FAN coordinators (n = 92) completed implementation surveys regarding opportunities, policies, messages, and pastor support for physical activity (PA) and healthy eating (HE) at baseline and 12 months. FAN coordinators and pastors (n = 93) completed CFIR-based measures at baseline, immediate post-training, and 12 months. Repeated measures ANOVAs tested change in PA and HE implementation composite scores; Cohen’s d indicated magnitude of change. Mixed model linear regression tested whether CFIR items predicted 12-month implementation, controlling for baseline implementation. PA (d = 1.42) and HE (d = 2.05) implementation increased significantly over time. PA and HE implementation were significantly greater in predominantly African American (versus White) congregations, and HE implementation was greater in churches with &lt;500 members. FAN coordinators’ ratings of the inner setting (networks/communication, culture, tension for change, organizational rewards, readiness, and congregant needs) and implementation process (engaging opinion leaders and champions) domains were most predictive of implementation outcomes. Few pastor ratings related to implementation outcomes. This study identified constructs, guided by CFIR, that may be important for understanding PA and HE implementation in churches. Future studies will need to test them for replication. Greater changes in implementation outcomes among African American churches underscores the potential of promoting health equity through this setting.
Impacts of experimental defoliation on native and invasive saplings: are native species more resilient to canopy disturbance?
Authors: Hinman Elise D , Fridley Jason D 
Published: March 2020

AbstractMany non-native, invasive woody species in mesic forests of North America are both shade tolerant and more productive than their native counterparts, but their ability to tolerate disturbances remains unclear. In particular, complete defoliation associated with herbivory and extreme weather events may have larger impacts on invaders if natives maintain greater resource reserves to support regrowth. On the other hand, invaders may be more resilient to partial defoliation by means of upregulation of photosynthesis or may be better able to take advantage of canopy gaps to support refoliation. Across a light gradient, we measured radial growth, new leaf production, non-structural carbohydrates (NSCs), chlorophyll content and survival in response to varying levels of defoliation in saplings of two native and two invasive species that commonly co-occur in deciduous forests of Eastern North America. Individuals were subjected to one of the four leaf removal treatments: no-defoliation controls, 50% defoliation over three growing seasons, 100% defoliation over one growing season and 100% defoliation over two growing seasons. Contrary to our hypothesis, native and invasive species generally did not differ in defoliation responses, although invasive species experienced more pronounced decreases in leaf chlorophyll following full defoliation and native species’ survival was more dependent on light availability. Radial growth progressively decreased with increasing defoliation intensity, and refoliation mass was largely a function of sapling size. Survival rates for half-defoliated saplings did not differ from controls (90% of saplings survived), but survival rates in fully defoliated individuals over one and two growing seasons were reduced to 45 and 15%, respectively. Surviving defoliated saplings generally maintained control NSC concentrations. Under high light, chlorophyll concentrations were higher in half-defoliated saplings compared with controls, which may suggest photosynthetic upregulation. Our results indicate that native and invasive species respond similarly to defoliation, despite the generally faster growth strategy of invaders.
Do Temporal Trends in Cancer Incidence Reveal Organ System Connections for Cancer Etiology?
Authors: Yang Wan , Terry Mary Beth 
Published: March 2020

Background:
Recent studies have reported substantial increases in cancer incidence in young adults under 40 years in the United States.

Methods:
We applied hierarchical cluster analysis to identify cancer anatomical clustering, for 48 anatomic sites, using incidence trends since 1973 for 25- to 39-year-olds.

Results:
Temporal trends mapped to three major clusters in men involving six organ systems (digestive, endocrine, urinary, blood, respiratory, and male genital) and one cluster in women involving five systems (digestive, endocrine, urinary, female genital, central nervous system). For both men and women, kidney, thyroid, and colorectal cancers consistently clustered for all ages 25–39 and for each 5-year age subgroup. Further, several cancers linked to the endocrine and digestive systems (three in men and six in women) had highly consistent temporal incidence trends.

Conclusions:
These findings suggest that there may be organ system connections for cancers of the endocrine and digestive systems; etiologic approaches focused on clusters of cancers rather than individual cancers may prove fruitful.