bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Diagnostics and Mobile Health in Laboratory Medicine: An International Federation of Clinical Chemistry and Laboratory Medicine Survey on Current Practice and Future Perspectives
Authors: Desiere Frank , Kowalik Katarzyna , Fassbind Christian , Assaad Ramy Samir , Füzéry Anna K , Gruson Damien , Heydlauf Michael , Kotani Kazuhiko , Nichols James H , Uygun Zihni Onur , Gouget Bernard 
Published: March 2021

Abstract

Background
A survey of IFCC members was conducted to determine current and future perspectives on digital innovations within laboratory medicine and healthcare sectors.

Methods
Questions focused on the relevance of digital diagnostic solutions, implementation and barriers to adopting digital technologies, and supplier roles in supporting innovation. Digital diagnostic market segments were defined by solution recipient (laboratory, clinician, patient/consumer, payor) and proximity to core laboratory operations.

Results
Digital solutions were of active interest for &gt;90% of respondents. Although solutions to improve core operations were ranked as the most relevant currently, a future shift to technologies beyond core laboratory expertise is expected. A key area of potential differentiation for laboratory customers was clinical decision support. Currently, laboratories collaborate strongly with suppliers of laboratory integration software and information systems, with high expectations for future collaboration in clinical decision support, disease self-management, and population health management. Asia Pacific countries attributed greater importance to adopting digital solutions than those in other regions. Financial burden was the most commonly cited challenge in implementing digital solutions.

Conclusions
Specialists in laboratory medicine are proactively approaching digital innovations and transformation, and there is high enthusiasm and expectation for further collaboration with suppliers and healthcare professionals beyond current core laboratory expertise.
Phylogeography of Cedros and Tiburón Island Mule Deer in North America’s Desert Southwest
Authors: Alminas Ona S V , Heffelfinger James R , Statham Mark J , Latch Emily K 
Published: March 2021

AbstractThough mule deer (Odocoileus hemionus) persist in robust populations throughout most of their North American distribution, habitat loss, unregulated hunting, and other factors have reduced their historical range in México. Two of the 6 putative subspecies inhabiting México’s deserts and Baja California peninsula are of conservation concern, occupying islands in the Pacific Ocean (Odocoileus hemionus cerrosensis on Cedros Island: endangered) and Sea of Cortés (Odocoileus hemionus sheldoni on Tiburón Island: threatened). Focusing on the desert southwest (n = 448), we sampled Tiburón (n = 22) and Cedros (n = 15) Island mule deer using contemporary samples and natural history museum specimens to complete a phylogeographic evaluation of the species complex, and assess the phylogeography of these insular subspecies. Both insular subspecies formed endemic haplotype lineages, consistent with island biogeographic theory. Bayesian skyline plots were consistent with Holocene demographic expansion. Cedros Island deer were genetically most similar to adjacent mainland Baja California deer, but exhibited a suite of unique haplotypes and reduced genetic variation. Tiburón Island deer haplotypes unexpectedly nested within a mainland lineage found in distant New Mexico, rather than the adjacent mainland Sonoran lineage. Such findings suggest the importance of postglacial climate fluctuations and biotic community turnover in the phylogeographic history of mule deer in the desert southwest. Our genetic data corroborates cultural, archaeological, and phenotypic evidence supporting Cedros and Tiburón deer endemicity and subspecies status. Reduced genetic variation, divergence from mainland populations, and demographic trends on both islands indicate that conservation, monitoring, and management are critical to ensure persistence of these endemic insular subspecies.
Investor Obligations in Special Economic Zones: Legal Status, Typology, and Functional Analysis
Authors: Lam Joanna , Guo Rui 
Published: March 2021

ABSTRACT
The article discusses various types of investor obligations in special economic zones and examines how they are utilized as instruments for devising development policies. It presents the evolution of regulatory models and practices related to investor obligations in the context of the unilateral character of the legal framework of the zones. The article distinguishes between two types of investor obligations. The first includes commitments focused on quantifiable aspects of economic performance of the investor in the host country, such as the maintenance of a pre-determined level of investment or the creation of a specific number of jobs. The second category of investor obligations is those containing qualitative goals that contribute to the host country’s developmental objectives, such as workforce welfare commitments, environmental standards, and technology transfers. Case studies of Shenzhen, Poland, and Tanzania are analysed to demonstrate how relevant regulatory practices have evolved over time. The case studies are drawn from three different phases of the global proliferation of special economic zones and reflect the regional diversity of the zones.
NTRK Fusions Can Co-Occur With H3K27M Mutations and May Define Druggable Subclones Within Diffuse Midline Gliomas
Authors: Dahl Nathan A , Donson Andrew M , Sanford Bridget , Wang Dong , Walker Faye M , Gilani Ahmed , Foreman Nicholas K , Tinkle Christopher L , Baker Suzanne J , Hoffman Lindsey M , Venkataraman Sujatha , Vibhakar Rajeev 
Published: March 2021

Abstract
Diffuse midline gliomas (DMGs) are incurable pediatric tumors with extraordinarily limited treatment options. Decades of clinical trials combining conventional chemotherapies with radiation therapy have failed to improve these outcomes, demonstrating the need to identify and validate druggable biologic targets within this disease. NTRK1/2/3 fusions are found in a broad range of pediatric cancers, including high-grade gliomas and a subset of DMGs. Phase 1/2 studies of TRK inhibitors have demonstrated good tolerability, effective CNS penetration, and promising objective responses across all patients with TRK fusion-positive cancers, but their use has not been explored in TRK fusion-positive DMG. Here, we report 3 cases of NTRK fusions co-occurring within H3K27M-positive pontine diffuse midline gliomas. We employ a combination of single-cell and bulk transcriptome sequencing from TRK fusion-positive DMG to describe the phenotypic consequences of this co-occurring alteration. We then use ex vivo short-culture assays to evaluate the potential response to TRK inhibition in this disease. Together, these data highlight the importance of routine molecular characterization of these highly aggressive tumors and identify a small subset of patients that may benefit from currently available targeted therapies.
Disentangling spatial, environmental and historical effects on tropical forest tree species turnover
Authors: Santos Alisson Borges Miranda , Maia Vinicius Andrade , de Souza Cléber Rodrigo , Fagundes Nathalle Cristine Alencar , Gianasi Fernanda Moreira , Pais Aurélio de Jesus Rodrigues , de Aguiar-Campos Natália , Pires Gabriela Gomes , Girardelli Diego Teixeira , Morel Jean Daniel , Morelli Mariana Caroline Moreira , Araújo Felipe de Carvalho , dos Santos Rubens Manoel 
Published: March 2021

Abstract

Aims
We aimed at disentangling the effects of spatial distance, current and past environmental dissimilarity, and their combinations on tree community taxonomic and phylogenetic turnover by addressing the following questions: (i) Is tree community taxonomic and phylogenetic turnover related to the indirect effects of spatial distance via environmental dissimilarity? (ii) Does tree community taxonomic and phylogenetic turnover respond to paleoclimate (Last Glacial Maximum and Mid-Holocene)?

Methods
The study was carried out in 14 Atlantic rainforest sites in Brazil (20.4 ha sampled) containing 615 tree species from 83 plant families. We obtained plot-level geographic coordinates and soil variables and site-level bioclimatic variables in the current, Mid-Holocene and Last Glacial Maximum. We used structural equation models with a distance-based approach to (i) test the direct effects of spatial distance and environmental dissimilarity and (ii) test the indirect effects of spatial distance via environmental dissimilarity on taxonomic (Bray–Curtis distance) and phylogenetic turnover (Comdist and Comdistnt distances).

Important Findings
Our results suggest a weak indirect effect of spatial distance via environmental dissimilarity on taxonomic and phylogenetic turnover. Tree community turnover was driven by the direct effects of neutral, niche-based and historical processes. Thus, we inferred that the paleoclimate (historical processes) promoted the selection of the clades that gave rise to the current flora, while spatial distances (neutral processes) limited the dispersal range of species from the regional pool and environmental conditions (niche-based processes) locally selected the taxa that are able to persist.
Medical Support of the Sinai Multinational Force and Observers: An Update, 2020
Authors: Gragg James , Sheehan Nathaniel , Weldon Louis , Vande Kamp Seth Vernon , Co Edgie-Mark 
Published: March 2021

ABSTRACT
The Multinational Force and Observers in Sinai is a 13-nation international peacekeeping organization with the mission to implement the security provisions of the 1979 Egyptian–Israeli Treaty of Peace and continues today after approximately four decades. Despite not having significant changes to its core mission of force health protection, the medical team has recently evolved to face several challenges, with a coronavirus pandemic and a fatal helicopter crash. This article describes the medical challenges and experiences of the medical team from August 2019 to December 2020, highlighting changes from previous years. This article also updates three previous articles on the subject published in Military Medicine in 1983, 1991, and 2003.
Maximum black hole mass across cosmic time
Authors: Vink Jorick S , Higgins Erin R , Sander Andreas A C , Sabhahit Gautham N 
Published: March 2021

ABSTRACT
At the end of its life, a very massive star is expected to collapse into a black hole (BH). The recent detection of an 85  M⊙ BH from the gravitational wave event GW 190521 appears to present a fundamental problem as to how such heavy BHs exist above the approximately 50  M⊙ pair-instability (PI) limit where stars are expected to be blown to pieces with no remnant left. Using mesa, we show that for stellar models with non-extreme assumptions, 90–100  M⊙ stars at reduced metallicity ($Z/\mbox{ $\mathrm{Z}_{\odot }$}\le 0.1$) can produce blue supergiant progenitors with core masses sufficiently small to remain below the fundamental PI limit, yet at the same time lose an amount of mass via stellar winds that is small enough to end up in the range of an ‘impossible’ 85  M⊙ BH. The two key points are the proper consideration of core overshooting and stellar wind physics with an improved scaling of mass-loss with iron (Fe) contents characteristic for the host galaxy metallicity. Our modelling provides a robust scenario that not only doubles the maximum BH mass set by PI, but also allows us to probe the maximum stellar BH mass as a function of metallicity and cosmic time in a physically sound framework.
Dynamical dust traps in misaligned circumbinary discs: analytical theory and numerical simulations
Authors: Longarini Cristiano , Lodato Giuseppe , Toci Claudia , Aly Hossam 
Published: March 2021

ABSTRACT
Recent observations have shown that circumbinary discs can be misaligned with respect to the binary orbital plane. The lack of spherical symmetry, together with the non-planar geometry of these systems, causes differential precession which might induce the propagation of warps. While gas dynamics in such environments is well understood, little is known about dusty discs. In this work, we analytically study the problem of dust traps formation in misaligned circumbinary discs. We find that pile-ups may be induced not by pressure maxima, as the usual dust traps, but by a difference in precession rates between the gas and dust. Indeed, this difference makes the radial drift inefficient in two locations, leading to the formation of two dust rings whose position depends on the system parameters. This phenomenon is likely to occur to marginally coupled dust particles (St ≳ 1) as both the effect of gravitational and drag force are considerable. We then perform a suite of 3D Smoothed Particle Hydrodynamics (SPH) numerical simulations to compare the results with our theoretical predictions. We explore the parameter space, varying stellar mass ratio, disc thickness, radial extension, and we find a general agreement with the analytical expectations. Such dust pile-up prevents radial drift, fosters dust growth and may thus promote the planet formation in circumbinary discs.
The proliferation of space objects is a rapidly increasing source of artificial night sky brightness
Authors: Kocifaj M , Kundracik F , Barentine J C , Bará S 
Published: March 2021

ABSTRACT
The population of artificial satellites and space debris orbiting the Earth imposes non-negligible constraints on both space operations and ground-based optical and radio astronomy. The ongoing deployment of several satellite ‘mega-constellations’ in the 2020s represents an additional threat that raises significant concerns. The expected severity of its unwanted consequences is still under study, including radio interference and information loss by satellite streaks appearing in science images. In this Letter, we report a new skyglow effect produced by space objects: increased night sky brightness caused by sunlight reflected and scattered by that large set of orbiting bodies whose direct radiance is a diffuse component when observed with the naked eye or with low angular resolution photometric instruments. According to our preliminary estimates, the zenith luminance of this additional light pollution source may have already reached ∼20 $\mu$cd m−2, which amounts to an approximately 10 per cent increase over the brightness of the night sky determined by natural sources of light. This is the critical limit adopted in 1979 by the International Astronomical Union for the light pollution level not to be exceeded at the sites of astronomical observatories.
Nse5/6 is a negative regulator of the ATPase activity of the Smc5/6 complex
Authors: Hallett Stephen T , Schellenberger Pascale , Zhou Lihong , Beuron Fabienne , Morris Ed , Murray Johanne M , Oliver Antony W 
Published: March 2021

AbstractThe multi-component Smc5/6 complex plays a critical role in the resolution of recombination intermediates formed during mitosis and meiosis, and in the cellular response to replication stress. Using recombinant proteins, we have reconstituted a series of defined Saccharomyces cerevisiae Smc5/6 complexes, visualised them by negative stain electron microscopy, and tested their ability to function as an ATPase. We find that only the six protein ‘holo-complex’ is capable of turning over ATP and that its activity is significantly increased by the addition of double-stranded DNA to reaction mixes. Furthermore, stimulation is wholly dependent on functional ATP-binding pockets in both Smc5 and Smc6. Importantly, we demonstrate that budding yeast Nse5/6 acts as a negative regulator of Smc5/6 ATPase activity, binding to the head-end of the complex to suppress turnover, irrespective of the DNA-bound status of the complex.
Risk Factors, Clinical Features, and Polygenic Risk Scores in Schizophrenia and Schizoaffective Disorder Depressive-Type
Authors: Dennison Charlotte A , Legge Sophie E , Hubbard Leon , Lynham Amy J , Zammit Stanley , Holmans Peter , Cardno Alastair G , Owen Michael J , O’Donovan Michael C , Walters James T R 
Published: March 2021

Abstract
There is controversy about the status of schizoaffective disorder depressive-type (SA-D), particularly whether it should be considered a form of schizophrenia or a distinct disorder. We aimed to determine whether individuals with SA-D differ from individuals with schizophrenia in terms of demographic, premorbid, and lifetime clinical characteristics, and genetic liability to schizophrenia, depression, and bipolar disorder. Participants were from the CardiffCOGS sample and met ICD-10 criteria for schizophrenia (n = 713) or SA-D (n = 151). Two samples, Cardiff Affected-sib (n = 354) and Cardiff F-series (n = 524), were used for replication. For all samples, phenotypic data were ascertained through structured interview, review of medical records, and an ICD-10 diagnosis made by trained researchers. Univariable and multivariable logistic regression models were used to compare individuals with schizophrenia and SA-D for demographic and clinical characteristics, and polygenic risk scores (PRS). In the CardiffCOGS, SA-D, compared to schizophrenia, was associated with female sex, childhood abuse, history of alcohol dependence, higher functioning Global Assessment Scale (GAS) score in worst episode of psychosis, lower functioning GAS score in worst episode of depression, and reduced lifetime severity of disorganized symptoms. Individuals with SA-D had higher depression PRS compared to those with schizophrenia. PRS for schizophrenia and bipolar disorder did not significantly differ between SA-D and schizophrenia. Compared to individuals with schizophrenia, individuals with SA-D had higher rates of environmental and genetic risk factors for depression and a similar genetic liability to schizophrenia. These findings are consistent with SA-D being a sub-type of schizophrenia resulting from elevated liability to both schizophrenia and depression.
Knowledge Transfers from Federally Funded Research and Development Centers
Authors: Link Albert N 
Published: March 2021

Abstract
The findings from a study of the relationship between postdoctoral students and R&D at Federally Funded Research and Development Centers (FFRDCs) are presented in this paper. The goal of the study is not only to understand better knowledge transfers from publicly supported R&D but also to estimate the returns to R&D conducted in federally funded laboratories. Using public domain data related to FFRDCs, published by the US National Science Foundation, the R&D elasticity of doctoral students is estimated over the years 2010–2019 to be about 0.85. This estimate compares well to previous studies of the returns to publicly funded R&D.
Genomic exploration of the targets of FOXL2 and ESR2 unveils their implication in cell migration, invasion, and adhesion
Authors: Herman Laetitia , Legois Bérangère , Todeschini Anne‐Laure , Veitia Reiner A. 
Published: March 2021

AbstractFOXL2 and ESR2 are key transcriptional regulators in ovarian granulosa cells. To explore their transcriptional roles and their interplay, we have depleted Foxl2 and Esr2 in mouse primary granulosa cells to assess their ability to bind their targets and/or to modulate gene expression and cellular functions. We show that FOXL2 is involved in a large number of regulatory actions essential for the maintenance of granulosa cell fate. A parallel ChIP‐seq analysis showed that FOXL2 mainly binds to sites located in intergenic regions quite far from its targets. A bioinformatic analysis demonstrated that FOXL2‐activated genes were enriched in peaks associated with the H3K27ac mark, whereas FOXL2‐repressed genes were not, suggesting that FOXL2 can activate transcription through binding to enhancer sites. We also identified about 500 deregulated genes upon Esr2 silencing, of which one third are also targets of FOXL2. We provide evidence showing that both factors modulate, through a coherent feed‐forward loop, a number of common targets. Many of the FOXL2/ESR2 targets are involved in cell motility and, consistently, granulosa cells depleted for either Foxl2 or Esr2 exhibit decreased migration, invasion and adhesion. This effect is paralleled by the depletion of their target Phactr1, involved in actin cytoskeleton dynamics. Our analysis expands the number of direct and indirect transcriptional targets of both FOXL2 and ESR2, which deserve investigation in the context of adult‐type granulosa cell tumors whose molecular diagnostic hallmark is the presence of the C134W FOXL2 pathogenic variant.
Reduced electron transport chain complex I protein abundance and function in Mfn2‐deficient myogenic progenitors lead to oxidative stress and mitochondria swelling
Authors: Luo Nanjian , Yue Feng , Jia Zhihao , Chen Jingjuan , Deng Qing , Zhao Yongju , Kuang Shihuan 
Published: March 2021

AbstractMitochondrial remodeling through fusion and fission is crucial for progenitor cell differentiation but its role in myogenesis is poorly understood. Here, we characterized the function of mitofusin 2 (Mfn2), a mitochondrial outer membrane protein critical for mitochondrial fusion, in muscle progenitor cells (myoblasts). Mfn2 expression is upregulated during myoblast differentiation in vitro and muscle regeneration in vivo. Targeted deletion of Mfn2 gene in myoblasts (Mfn2MKO) increases oxygen‐consumption rates (OCR) associated with the maximal respiration and spare respiratory capacity, and increased levels of reactive oxygen species (ROS). Skeletal muscles of Mfn2MKO mice exhibit robust mitochondrial swelling with normal mitochondrial DNA content. Additionally, mitochondria isolated from Mfn2MKO muscles have reduced OCR at basal state and for complex I respiration, associated with decreased levels of complex I proteins NDUFB8 (NADH ubiquinone oxidoreductase subunit B8) and NDUFS3 (NADH ubiquinone oxidoreductase subunit S3). However, Mfn2MKO has no obvious effects on myoblast differentiation, muscle development and function, and muscle regeneration. These results demonstrate a novel role of Mfn2 in regulating mitochondrial complex I protein abundance and respiratory functions in myogenic progenitors and myofibers.
Effects of R‐flurbiprofen and the oxygenated metabolites of endocannabinoids in inflammatory pain mice models
Authors: Buisseret Baptiste , Guillemot‐Legris Owein , Ben Kouidar Youssef , Paquot Adrien , Muccioli Giulio G. , Alhouayek Mireille 
Published: March 2021

AbstractPain is one of the cardinal signs accompanying inflammation. The prostaglandins (PGs), synthetized from arachidonic acid by cyclooxygenase (COX)‐2, are major bioactive lipids implicated in inflammation and pain. However, COX‐2 is also able to metabolize other lipids, including the endocannabinoids 2‐arachidonoylglycerol (2‐AG) and anandamide (AEA), to give glycerol ester (PG‐G) and ethanolamide (PG‐EA) derivatives of the PGs. Consequently, COX‐2 can be considered as a hub not only controlling PG synthesis, but also PG‐G and PG‐EA synthesis. As they were more recently characterized, these endocannabinoid metabolites are less studied in nociception compared to PGs. Interestingly R‐profens, previously considered as inactive enantiomers of nonsteroidal anti‐inflammatory drugs (NSAIDs), are substrate‐selective COX inhibitors. Indeed, R‐flurbiprofen can selectively block PG‐G and PG‐EA production, without affecting PG synthesis from COX‐2. Therefore, we compared the effect of R‐flurbiprofen and S‐flurbiprofen in models of inflammatory pain triggered by local administration of lipopolysaccharides (LPS) and carrageenan in mice. Remarkably, the effects of flurbiprofen enantiomers on mechanical hyperalgesia seem to depend on (i) the inflammatory stimuli, (ii) the route of administration, and (iii) the timing of administration. We also assessed the effect of administration of the PG‐Gs, PG‐EAs, and PGs on LPS‐induced mechanical hyperalgesia. Our data support the interest of studying the nonhydrolytic endocannabinoid metabolism in the context of inflammatory pain.