bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming barriers to the adoption and implementation of predictive modeling and machine learning in clinical care: what can we learn from US academic medical centers?
Authors: Watson Joshua , Hutyra Carolyn A , Clancy Shayna M , Chandiramani Anisha , Bedoya Armando , Ilangovan Kumar , Nderitu Nancy , Poon Eric G 
Published: April 2020

Abstract
There is little known about how academic medical centers (AMCs) in the US develop, implement, and maintain predictive modeling and machine learning (PM and ML) models. We conducted semi-structured interviews with leaders from AMCs to assess their use of PM and ML in clinical care, understand associated challenges, and determine recommended best practices. Each transcribed interview was iteratively coded and reconciled by a minimum of 2 investigators to identify key barriers to and facilitators of PM and ML adoption and implementation in clinical care. Interviews were conducted with 33 individuals from 19 AMCs nationally. AMCs varied greatly in the use of PM and ML within clinical care, from some just beginning to explore their utility to others with multiple models integrated into clinical care. Informants identified 5 key barriers to the adoption and implementation of PM and ML in clinical care: (1) culture and personnel, (2) clinical utility of the PM and ML tool, (3) financing, (4) technology, and (5) data. Recommendation to the informatics community to overcome these barriers included: (1) development of robust evaluation methodologies, (2) partnership with vendors, and (3) development and dissemination of best practices. For institutions developing clinical PM and ML applications, they are advised to: (1) develop appropriate governance, (2) strengthen data access, integrity, and provenance, and (3) adhere to the 5 rights of clinical decision support. This article highlights key challenges of implementing PM and ML in clinical care at AMCs and suggests best practices for development, implementation, and maintenance at these institutions.
Goal Conflict Encourages Work and Discourages Leisure
Authors: Etkin Jordan , Memmi Sarah A 
Published: April 2020

AbstractLeisure is desirable and beneficial, yet consumers frequently forgo leisure in favor of other activities—namely, work. Why? We propose that goal conflict plays an important role. Seven experiments demonstrate that perceiving greater goal conflict shapes how consumers allocate time to work and leisure—even when those activities are unrelated to the conflicting goals. This occurs because goal conflict increases reliance on salient justifications, influencing how much time people spend on subsequent, unrelated activities. Because work tends to be easier to justify and leisure harder to justify, goal conflict increases time spent on work and decreases time spent on leisure. Thus, despite the conflicting goals being independent of the specific work and leisure activities considered (i.e., despite goal conflict being “incidental”), perceiving greater goal conflict encourages work and discourages leisure. The findings further understanding of how consumers allocate time to work and leisure, incidental effects of goal conflict on decision-making, and the role of justification in consumer choice. They also have implications for the use of “time-saving” technologies and the marketing of leisure activities.
Multinational enterprises, industrial relatedness and employment in European regions
Authors: Cortinovis Nicola , Crescenzi Riccardo , van Oort Frank 
Published: April 2020

AbstractThis article investigates the link between multinational enterprises (MNEs) and employment in their host regions by cross-fertilising the literature on MNE externalities with the emerging body of research on industrial relatedness. The link between employment and MNE presence in the same and related industries is tested for European regions. The results suggest that cross-sectoral MNE spillovers are mediated through industrial relatedness and that they are positively and significantly associated with higher employment levels, independently of input–output relations. Our results indicate that regions characterised by lower factor prices are likely to benefit the most from the presence of multinationals in terms of employment, but these benefits are concentrated in high knowledge-intensive sectors, potentially fostering inequalities within less-developed economies.
Diffuse γ-ray emission from the vicinity of young massive star cluster RSGC 1
Authors: Sun Xiao-Na , Yang Rui-Zhi , Wang Xiang-Yu 
Published: April 2020

ABSTRACT
We report the Fermi Large Area Telescope (Fermi-LAT) detection of the γ-ray emission towards the young massive star cluster RSGC 1. Using the latest source catalogue and diffuse background models, we found that the diffuse γ-ray emission in this region can be resolved into three different components. The GeV γ-ray emission from the region HESS J1837-069 has a photon index of 1.83 ± 0.08. Combining with the HESS and MAGIC data, we argue that the γ-ray emission in this region likely originates from a pulsar wind nebula. The γ-ray emission from the north-west part (region A) can be modelled by an ellipse with the semimajor and semiminor axes of 0.5° and 0.25°, respectively. The GeV emission has a hard spectrum with a photon index of about −2 and partially coincides with the TeV source MAGIC J1835-069. The possible origin of the γ-ray emission in this region is the interaction of the cosmic rays (CRs) accelerated by SNR G24.7+0.6 or/and the OB cluster G25.18+0.26 with the surrounding gas clouds. The GeV γ-ray emission from the south-east region (region B) can be modelled as an ellipse with the semimajor and semiminor axes of 0.9° and 0.5°, respectively, and also reveals a hard γ-ray spectrum. We argue that the most probable origin is the interaction of the accelerated protons in the young massive star cluster RSGC 1 with ambient gas clouds, and the total CR proton energy is estimated to be as high as ${\sim}1\times 10^{50}\ \rm erg$.
Time-dependent high-energy gamma-ray signal from accelerated particles in core-collapse supernovae: the case of SN 1993J
Authors: Cristofari P , Renaud M , Marcowith A , Dwarkadas V V , Tatischeff V 
Published: April 2020

ABSTRACT
Some core-collapse supernovae are likely to be efficient cosmic ray accelerators up to the PeV range, and therefore, to potentially play an important role in the overall Galactic cosmic ray population. The TeV gamma-ray domain can be used to study particle acceleration in the multi-TeV and PeV range. This motivates the study of the detectability of such supernovae by current and future gamma-ray facilities. The gamma-ray emission of core-collapse supernovae strongly depends on the level of the two-photon annihilation process: high-energy gamma-ray photons emitted at the expanding shock wave following the supernova explosion can interact with soft photons from the supernova photosphere through the pair production channel, thereby strongly suppressing the flux of gamma-rays leaving the system. In the case of SN 1993J, whose photospheric and shock-related parameters are well measured, we calculate the temporal evolution of the expected gamma-ray attenuation by accounting for the temporal and geometrical effects. We find the attenuation to be of about 10 orders of magnitude in the first few days after the supernova explosion. The probability of detection of a supernova similar to SN 1993J with the Cherenkov Telescope Array is highest if observations are performed either earlier than 1 d, or later than 10 d after the explosion, when the gamma-ray attenuation decreases to about two orders of magnitude.
Life-Course Monitoring of Endogenous Phytohormone Levels under Field Conditions Reveals Diversity of Physiological States among Barley Accessions
Authors: Hirayama Takashi , Saisho Daisuke , Matsuura Takakazu , Okada Satoshi , Takahagi Kotaro , Kanatani Asaka , Ito Jun , Tsuji Hiroyuki , Ikeda Yoko , Mochida Keiichi 
Published: April 2020

Abstract
Agronomically important traits often develop during the later stages of crop growth as consequences of various plant–environment interactions. Therefore, the temporal physiological states that change and accumulate during the crop’s life course can significantly affect the eventual phenotypic differences in agronomic traits among crop varieties. Thus, to improve productivity, it is important to elucidate the associations between temporal physiological responses during the growth of different crop varieties and their agronomic traits. However, data representing the dynamics and diversity of physiological states in plants grown under field conditions are sparse. In this study, we quantified the endogenous levels of five phytohormones — auxin, cytokinins (CKs), ABA, jasmonate and salicylic acid — in the leaves of eight diverse barley (Hordeum vulgare) accessions grown under field conditions sampled weekly over their life course to assess the ongoing fluctuations in hormone levels in the different accessions under field growth conditions. Notably, we observed enormous changes over time in the development-related plant hormones, such as auxin and CKs. Using 3′ RNA-seq-based transcriptome data from the same samples, we investigated the expression of barley genes orthologous to known hormone-related genes of Arabidopsis throughout the life course. These data illustrated the dynamics and diversity of the physiological states of these field-grown barley accessions. Together, our findings provide new insights into plant–environment interactions, highlighting that there is cultivar diversity in physiological responses during growth under field conditions.
Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility
Authors: Aue Arman , Szelinski Franziska , Weißenberg Sarah Y , Wiedemann Annika , Rose Thomas , Lino Andreia C , Dörner Thomas 
Published: April 2020

Abstract

Objectives
SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity.

Methods
Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren’s (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated.

Results
SLE patients showed substantially higher STAT1 but not pSTAT1 in B- and T-cell subsets. Increased STAT1 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.

Conclusion
Enhanced expression of STAT1 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold a promise to block STAT1 expression and control plasmablast induction in SLE.
TO USE OR NOT USE PATIENT SHIELDING ON PREGNANT WOMEN UNDERGOING CT PULMONARY ANGIOGRAPHY: A PHANTOM STUDY
Authors: Begano Dino , Söderberg Marcus , Bolejko Anetta 
Published: April 2020

Abstract
Pregnancy increases the risk of pulmonary embolism. Computed tomography pulmonary angiography (CTPA) is used for diagnosis. CT generates ionising radiation, and thus, abdominal shielding may be used. This phantom study investigated the effects of patient shielding and scan length reduction on the fetal and maternal ionising radiation dose from CTPA. The absorbed dose to the fetus was measured using thermoluminescent dosemeters. Estimated effective doses to the pregnant patient were based on the dose-length products. Shielding increased both the effective dose to the patient by 47% and the mean absorbed dose to the fetus (0.10 vs. 0.12 mGy; p &lt; 0.001) compared with unshielded standard CTPA, as it affected the automatic exposure control. Shielded short CTPA marginally lowered only the mean fetal absorbed dose (0.03 vs. 0.02 mGy; p = 0.018). Shortening the scan reduced the fetal absorbed dose most effectively by 70% (0.10 vs. 0.03 mGy; p = 0.006), compared with the standard unshielded scan. Shielding modestly reduces fetal radiation dose but may compromise automatic exposure control, possibly increasing the maternal and fetal radiation dose. Shortening the scan is beneficial, assuming anatomical coverage is secured.
Impact of a fumaric acid and palm oil additive on beef cattle performance and carcass characteristics in diets containing increasing concentrations of corn silage1
Authors: Wilson Hannah Carissa , Hilscher Fred H , McPhillips Levi J , Boyd Bradley M , Watson Andrea K , Erickson Galen E , MacDonald Jim C 
Published: April 2020

Abstract
A feedlot study was conducted comparing a natural feed additive at varying corn silage (CS) inclusions on receiving and finishing cattle performance. The study utilized 480 crossbred steers (initial shrunk body weight [BW] = 296 kg; SD = 24.1 kg) in 48 pens with 10 steers/pen and 8 pens per treatment. Treatments were designed as a 2 × 3 factorial with 3 inclusions of CS (14%, 47%, 80%; dry matter [DM] basis) with or without (+, −) the inclusion of a feed additive containing fumaric acid and palm oil (FAPO). All treatment diets contained 16% modified distillers grains plus solubles and 4% supplement with dry-rolled corn replacing CS on a DM basis. All steers were fed the 80 CS diet and adapted to 47% and 14% CS over a 10- and 24-d period, respectively. Cattle fed 80 CS were fed for 238 days, 47 CS for 195 days, and 14% CS were fed for 168 days to a common backfat of 1.28 cm (P ≥ 0.59). There were no interactions for CS inclusion and the inclusion of FAPO on final body weight (FBW), DMI, ADG, G:F, hot carcass weight (HCW), LM area, marbling, or calculated yield grade (CYG; P ≥ 0.15). There was no significant difference for FBW, DMI, ADG, G:F, HCW, marbling, or CYG for cattle fed with or without FAPO (P ≥ 0.13). However, there was a quadratic response for FBW, ADG, G:F, HCW, marbling, and CYG with increased inclusion of CS (P ≤ 0.04). Inclusion of FAPO had no effect on performance. Feeding CS at greater inclusions decreased daily gain and feed efficiency but increased FBW when fed to an equal fat endpoint. CS gave greater returns ($/animal) when fed at 80% of diet DM. Feeding greater amounts of CS can be an economical way to finish cattle. In this study, FAPO did not affect animal performance, carcass characteristics, or economic return.
Validation of a Lysis Buffer Containing 4 M Guanidinium Thiocyanate (GITC)/ Triton X-100 for Extraction of SARS-CoV-2 RNA for COVID-19 Testing: Comparison of Formulated Lysis Buffers Containing 4 to 6 M GITC, Roche External Lysis Buffer and Qiagen RTL Lysis Buffer
Authors: Scallan Martina F. , Dempsey Catherine , MacSharry John , O’Callaghan Isabelle , O’Connor Paula M. , Horgan Conor P. , Durack Edel , Cotter Paul D. , Hudson Sarah , Moynihan Humphrey A. , Lucey Brigid 
Published: April 2020

AbstractThe COVID-19 pandemic has resulted in increased need for diagnostic testing using reverse transcriptase real-time PCR (RT-PCR). An exponential increase in demand has resulted in a shortage of numerous reagents in particular those associated with the lysis buffer required to extract the viral RNA. Herein, we describe a rapid collective effort by hospital laboratory scientists, academic researchers and the biopharma industry to generate a validated lysis buffer. We have formulated a 4M Guanidinium thiocyanate (GITC)/ Triton X-100 Lysis buffer which provides comparable results with the recommended reagents. This buffer will ease the burden on hospital labs in their heroic efforts to diagnose a large population of patients.
LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding
Authors: Schmid-Burgk Jonathan L. , Schmithausen Ricarda M. , Li David , Hollstein Ronja , Ben-Shmuel Amir , Israeli Ofir , Weiss Shay , Paran Nir , Wilbring Gero , Liebing Jana , Feldman David , Słabicki Mikołaj , Lippke Bärbel , Sib Esther , Borrajo Jacob , Strecker Jonathan , Reinhardt Julia , Hoffmann Per , Cleary Brian , Hölzel Michael , Nöthen Markus M. , Exner Martin , Ludwig Kerstin U. , Regev Aviv , Zhang Feng 
Published: April 2020

SummaryThe ongoing SARS-CoV-2 pandemic has already caused devastating losses. Exponential spread can be slowed by social distancing and population-wide isolation measures, but those place a tremendous burden on society, and, once lifted, exponential spread can re-emerge. Regular population-scale testing, combined with contact tracing and case isolation, should help break the cycle of transmission, but current detection strategies are not capable of such large-scale processing. Here we present a protocol for LAMP-Seq, a barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) method that is highly scalable. Individual samples are stabilized, inactivated, and amplified in three isothermal heat steps, generating barcoded amplicons that can be pooled and analyzeden masseby sequencing. Using unique barcode combinations per sample from a compressed barcode space enables extensive pooling, potentially further reducing cost and simplifying logistics. We validated LAMP-Seq on 28 clinical samples, empirically optimized the protocol and barcode design, and performed initial safety evaluation. Relying on world-wide infrastructure for next-generation sequencing, and in the context of population-wide sample collection, LAMP-Seq could be scaled to analyze millions of samples per day.
Single cell profiling of immature human postnatal thymocytes resolves the complexity of intra-thymic lineage differentiation and thymus seeding precursors
Authors: Lavaert Marieke , Liang Kai Ling , Vandamme Niels , Park Jong-Eun , Roels Juliette , Kowalczyk Monica S. , Li Bo , Ashenberg Orr , Tabaka Marcin , Dionne Danielle , Tickle Timothy L. , Slyper Michal , Rozenblatt-Rosen Orit , Vandekerckhove Bart , Leclercq Georges , Regev Aviv , Van Vlierberghe Pieter , Guilliams Martin , Teichmann Sarah A. , Saeys Yvan , Taghon Tom 
Published: April 2020

AbstractDuring postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone marrow derived hematopoietic progenitors that migrate through the bloodstream. In human, the nature of these thymus immigrants has remained unclear. Here, we employ single-cell RNA sequencing on approximately 70.000 CD34+thymocytes to unravel the heterogeneity of the human immature postnatal thymocytes. Integration of bone marrow and peripheral blood precursors datasets identifies several putative thymus seeding precursors that display heterogeneity for currently used surface markers as revealed by CITEseq. Besides T cell precursors, we discover branches of intrathymic developing dendritic cells with predominantly plasmacytoid DCs. Trough trajectory inference, we delineate the transcriptional dynamics underlying early human T-lineage development from which we predict transcription factor modules that drive stage-specific steps of human T cell development. Thus, our work resolves the heterogeneity of thymus seeding precursors in human and reveals the molecular mechanisms that drive theirin vivocell fate.
Adaptive mitochondrial regulation of the proteasome
Authors: Meul Thomas , Berschneider Korbinian , Schmitt Sabine , Mayr Christoph H. , Mattner Laura F. , Schiller Herbert B. , Yazgili Ayse , Wang Xinyuan , Lukas Christina , Prehn Cornelia , Adamski Jerzy , Graf Elisabeth , Schwarzmayr Thomas , Perocchi Fabiana , Kukat Alexandra , Trifunovic Aleksandra , Kremer Laura , Prokisch Holger , Popper Bastian , von Toerne Christine , Hauck Stefanie M. , Zischka Hans , Meiners Silke 
Published: April 2020

SummaryThe proteasome is the main proteolytic system for targeted protein degradation in the cell. Its function is fine-tuned according to cellular needs. Regulation of proteasome function by mitochondrial metabolism, however, is unknown.Here, we demonstrate that mitochondrial dysfunction reduces the assembly and activity of the 26S proteasome in the absence of oxidative stress. Impaired respiratory complex I function leads to metabolic reprogramming of the Krebs cycle and deficiency in aspartate. Aspartate supplementation activates assembly and activity of 26S proteasomes via transcriptional activation of the proteasome assembly factors p28 and Rpn6. This metabolic adaptation of 26S proteasome function involves sensing of aspartate via the mTORC1 pathway. Metformin treatment of primary human cells similarly reduced assembly and activity of 26S proteasome complexes, which was fully reversible and rescued by supplementation of aspartate or pyruvate. Of note, respiratory dysfunction conferred resistance towards the proteasome inhibitor Bortezomib.Our study uncovers a fundamental novel mechanism of how mitochondrial metabolism adaptively adjusts protein degradation by the proteasome. It thus unravels unexpected consequences of defective mitochondrial metabolism in disease or drug-targeted mitochondrial reprogramming for proteasomal protein degradation in the cell. As metabolic inhibition of proteasome function can be alleviated by treatment with aspartate or pyruvate, our results also have therapeutic implications.
Transcription-coupled repair inDrosophila melanogasteris independent of the mismatch repair pathway
Authors: Törmä Lauri , Burny Claire , Nolte Viola , Senti Kirsten-André , Schlötterer Christian 
Published: April 2020

AbstractTranscription-coupled repair (TCR) removes base damage on the transcribed strand of a gene to ensure a quick resumption of transcription. Based on the absence of key enzymes for TCR and empirical evidence, TCR was thought to be missing inDrosophila melanogaster. The recent demonstration of TCR in S2 cells raises the question about the involved genes. Since the mismatch repair (MMR) pathway serves a central role in TCR, at least inEscherichia coli, we studied the mutational signatures in flies with a deletion of the MMR genespellchecker1(spel1), a MutS homolog. Whole-genome sequencing of mutation accumulation (MA) lines obtained 7,345 new single nucleotide variants (SNVs) and 5,672 short indel mutations, the largest data set from an MA study inD. melanogaster. Based on the observed mutational strand-asymmetries, we conclude that TCR is still active withoutspel1. The operation of TCR is further confirmed by a negative association between mutation rate and gene expression. Surprisingly, the TCR signatures are detected for introns, but not for exons. We propose that an additional exon-specific repair pathway is masking the signature of TCR. This study presents the first step towards understanding the molecular basis of TCR inDrosophila melanogaster.