bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding How Clinicians Use a New Web-based Tool for Disseminating Evidence-Based Practices for the Treatment of PTSD: The PTSD Clinicians Exchange
Authors: Coleman Julia L , Marceau Lisa , Zincavage Rebekah , Magnavita Ashley M , Ambrosoli James , Shi Ling , Simon Erica , Ortigo Kile , Clarke-Walper Kristina , Penix Elizabeth , Wilk Joshua , Ruzek Josef I , Rosen Raymond C 
Published: February 2020

Abstract

Introduction
Web-based interventions hold great promise for the dissemination of best practices to clinicians, and investment in these resources has grown exponentially. Yet, little research exists to understand their impact on intended objectives.

Materials & Methods
The Post-Traumatic Stress Disorder (PTSD) Clinicians Exchange is a website to support clinicians treating veterans and active duty military personnel with PTSD, evaluated in a randomized controlled trial (N = 605). This manuscript explores how a subset of clinicians, those who utilized the intervention (N = 148), engaged with it by examining detailed individual-level web analytics and qualitative feedback. Stanford University and New England Research Institutes Institutional Review Boards approved this study.

Results
Only 32.7% of clinicians randomized to the intervention ever accessed the website. The number of pages viewed was positively associated with changes from baseline to 12 months in familiarity (P = 0.03) and perceived benefit of practices (P = 0.02). Thus, engagement with the website did predict an improvement in practice familiarity and benefit outcomes despite low rates of use.

Conclusions
This study demonstrates the importance of methodologically rigorous evaluations of participant engagement with web-based interventions. These approaches provide insight into who accesses these tools, when, how, and with what results, which can be translated into their strategic design, evaluation, and dissemination.
Revisiting the reactivity between HCO and CH3 on interstellar grain surfaces
Authors: Enrique-Romero J , Álvarez-Barcia S , Kolb F J , Rimola A , Ceccarelli C , Balucani N , Meisner J , Ugliengo P , Lamberts T , Kästner J 
Published: February 2020

ABSTRACT
The formation of interstellar complex organic molecules is currently thought to be dominated by the barrierless coupling between radicals on the interstellar icy grain surfaces. Previous standard density functional theory (DFT) results on the reactivity between CH3 and HCO on amorphous water surfaces showed that the formation of CH4 + CO by H transfer from HCO to CH3 assisted by water molecules of the ice was the dominant channel. However, the adopted description of the electronic structure of the biradical (i.e. CH3/HCO) system was inadequate [without the broken-symmetry (BS) approach]. In this work, we revisit the original results by means of BS-DFT both in gas phase and with one water molecule simulating the role of the ice. Results indicate that the adoption of BS-DFT is mandatory to describe properly biradical systems. In the presence of the single water molecule, the water-assisted H transfer exhibits a high energy barrier. In contrast, CH3CHO formation is found to be barrierless. However, direct H transfer from HCO to CH3 to give CO and CH4 presents a very low energy barrier, hence being a potential competitive channel to the radical coupling and indicating, moreover, that the physical insights of the original work remain valid.
MHD-shock structures of astrospheres: λ Cephei -like astrospheres
Authors: Scherer K , Baalmann L R , Fichtner H , Kleimann J , Bomans D J , Weis K , Ferreira S E S , Herbst K 
Published: February 2020

ABSTRACT
The interpretation of recent observations of bow shocks around O-stars and the creation of corresponding models require a detailed understanding of the associated (magneto-)hydrodynamic structures. We base our study on 3D numerical (magneto-)hydrodynamical models, which are analysed using the dynamically relevant parameters, in particular, the (magneto)sonic Mach numbers. The analytic Rankine–Hugoniot relation for HD and MHD are compared with those obtained by the numerical model. In that context, we also show that the only distance which can be approximately determined is that of the termination shock, if it is an HD shock. For MHD shocks, the stagnation point does not, in general, lie on the inflow line, which is the line parallel to the inflow vector and passing through the star. Thus an estimate via the Bernoulli equation as in the HD case is, in general, not possible. We also show that in O-star astrospheres, distinct regions exist in which the fast, slow, Alfvénic, and sonic Mach numbers become lower than one, implying subslow magnetosonic as well as subfast and subsonic flows. Nevertheless, the analytic MHD Rankine–Hugoniot relations can be used for further studies of turbulence and cosmic ray modulation.
A search for the lenses in the Herschel Bright Sources (HerBS) sample
Authors: Bakx Tom J L C , Eales Stephen , Amvrosiadis Aristeidis 
Published: February 2020

ABSTRACT
Verifying that sub-mm galaxies are gravitationally lensed requires time-expensive observations with oversubscribed high-resolution observatories. Here, we aim to strengthen the evidence of gravitational lensing within the Herschel Bright Sources (HerBS) by cross-comparing their positions to optical (SDSS) and near-infrared (VIKING) surveys, in order to search for the foreground lensing galaxy candidates. Resolved observations of the brightest HerBS sources have already shown that most are lensed, and a galaxy evolution model predicts that ∼76 per cent of the total HerBS sources are lensed, although with the SDSS survey we are only able to identify the likely foreground lenses for 25 per cent of the sources. With the near-infrared VIKING survey, however, we are able to identify the likely foreground lenses for 57 per cent of the sources, and we estimate that 82 per cent of the HerBS sources have lenses on the VIKING images even if we cannot identify the lens in every case. We find that the angular offsets between lens and Herschel source are larger than that expected if the lensing is done by individual galaxies. We also find that the fraction of HerBS sources that are lensed falls with decreasing 500-micron flux density, which is expected from the galaxy evolution model. Finally, we apply our statistical VIKING cross-identification to the entire Herschel-ATLAS catalogue, where we also find that the number of lensed sources falls with decreasing 500-micron flux density.
Comparison of the efficacy of MOE and PMO modifications of systemic antisense oligonucleotides in a severe SMA mouse model
Authors: Sheng Lei , Rigo Frank , Bennett C Frank , Krainer Adrian R , Hua Yimin 
Published: February 2020

Abstract
Spinal muscular atrophy (SMA) is a motor neuron disease. Nusinersen, a splice-switching antisense oligonucleotide (ASO), was the first approved drug to treat SMA. Based on prior preclinical studies, both 2′-O-methoxyethyl (MOE) with a phosphorothioate backbone and morpholino with a phosphorodiamidate backbone—with the same or extended target sequence as nusinersen—displayed efficient rescue of SMA mouse models. Here, we compared the therapeutic efficacy of these two modification chemistries in rescue of a severe mouse model using ASO10-29—a 2-nt longer version of nusinersen—via subcutaneous injection. Although both chemistries efficiently corrected SMN2 splicing in various tissues, restored motor function and improved the integrity of neuromuscular junctions, MOE-modified ASO10-29 (MOE10-29) was more efficacious than morpholino-modified ASO10-29 (PMO10-29) at the same molar dose, as seen by longer survival, greater body-weight gain and better preservation of motor neurons. Time-course analysis revealed that MOE10-29 had more persistent effects than PMO10-29. On the other hand, PMO10-29 appears to more readily cross an immature blood-brain barrier following systemic administration, showing more robust initial effects on SMN2 exon 7 inclusion, but less persistence in the central nervous system. We conclude that both modifications can be effective as splice-switching ASOs in the context of SMA and potentially other diseases, and discuss the advantages and disadvantages of each.
High-throughput sleep phenotyping produces robust and heritable traits in Diversity Outbred mice and their founder strains
Authors: Keenan Brendan T , Galante Raymond J , Lian Jie , Simecek Petr , Gatti Daniel M , Zhang Lin , Lim Diane C , Svenson Karen L , Churchill Gary A , Pack Allan I 
Published: February 2020

AbstractStudy ObjectivesThis study describes high-throughput phenotyping strategies for sleep and circadian behavior in mice, including examinations of robustness, reliability, and heritability among Diversity Outbred (DO) mice and their eight founder strains.MethodsWe performed high-throughput sleep and circadian phenotyping in male mice from the DO population (n = 338) and their eight founder strains: A/J (n = 6), C57BL/6J (n = 14), 129S1/SvlmJ (n = 6), NOD/LtJ (n = 6), NZO/H1LtJ (n = 6), CAST/EiJ (n = 8), PWK/PhJ (n = 8), and WSB/EiJ (n = 6). Using infrared beam break systems, we defined sleep as at least 40 s of continuous inactivity and quantified sleep–wake amounts and bout characteristics. We developed assays to measure sleep latency in a new environment and during a modified Murine Multiple Sleep Latency Test, and estimated circadian period from wheel-running experiments. For each trait, broad-sense heritability (proportion of variability explained by all genetic factors) was derived in founder strains, while narrow-sense heritability (proportion of variability explained by additive genetic effects) was calculated in DO mice.ResultsPhenotypes were robust to different inactivity durations to define sleep. Differences across founder strains and moderate/high broad-sense heritability were observed for most traits. There was large phenotypic variability among DO mice, and phenotypes were reliable, although estimates of heritability were lower than in founder mice. This likely reflects important nonadditive genetic effects.ConclusionsA high-throughput phenotyping strategy in mice, based primarily on monitoring of activity patterns, provides reliable and heritable estimates of sleep and circadian traits. This approach is suitable for discovery analyses in DO mice, where genetic factors explain some proportion of phenotypic variation.
Update on chronic intestinal pseudo-obstruction
Authors: Zenzeri Letizia , Tambucci Renato , Quitadamo Paolo , Giorgio Valentina , De Giorgio Roberto , Di Nardo Giovanni 
Published: February 2020

Purpose of reviewChronic intestinal pseudo-obstruction (CIPO) is the most severe and disabling form of gastrointestinal dysmotility characterized by an impairment of coordinated propulsive activity in the gastrointestinal tract mimicking mechanical intestinal obstruction. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this rare disorder.Recent findingsThe present narrative review aims to summarize the current literature about the management of CIPO focusing on significant novelties about definition, epidemiology, diagnosis, and therapeutic options. The most significant advancement is a consensus on classification and dedicated diagnostic criteria for CIPO in children highlighting the distinctive features between adult and pediatric forms of CIPO (hence pediatric intestinal pseudo-obstruction). Despite no single diagnostic test is pathognomonic of CIPO and no recommended drug treatment is advised to improve gastrointestinal motility, recent reports suggest promising results in both diagnostic testing and therapy that might assist the diagnosis and help the management of patients with CIPO.SummaryThe articles referenced in this review will help in optimizing the clinical management of this rare and severe disease in adult population.
An opposing view to United States liver allocation problems with broader sharing
Authors: Goldberg David 
Published: February 2020

Purpose of review
Since 2014, the liver transplant community has been debating the pros and cons of broader sharing. Over the last 6 years, lung and heart transplantation have moved to broader sharing based on ‘zones’ or circles around a donor hospital, with the Organ Procurement and Transplantation Network (OPTN) approving a broader kidney sharing proposal in December of 2019 (set to be implemented in December 2020).

Recent findings
In 2017, the OPTN Board of Directors approved a broader sharing policy in liver transplantation that was rooted in expanding the first-line of liver sharing beyond the donor service area (DSA). Faced with the threat of litigation, this proposal was replaced with a circle-based sharing policy titled ‘Acuity Circles’. After a long legal challenge, the implementation of this new policy was delayed from April 2019 until February 2020.

Summary
In this review, concerns related to broader sharing in liver allocation will be addressed, in terms of the basis for broader sharing and the potential implications to liver transplantation, rooted in the Final Rule and concerns around variability in organ donation rates and access to the waiting list.
Current status of intestinal transplantation in East Asia
Authors: Hibi Taizo , Chen Yun , Kim Ji-il , Lee Myung Duk , Matsuura Toshiharu , Ueno Takehisa 
Published: February 2020

Purpose of review
Intestinal transplantation (ITx) activity remains low in East Asia. We conducted a multinational, retrospective study on patients who underwent ITx in Korea, Taiwan, and Japan, to provide an overview and to foresee future developments and collaborations in this region.

Recent findings
Total 71 ITx were performed in 67 patients. Living donor ITx was most commonly conducted in Japan (n = 13). Despite the low caseload, all three countries demonstrated acceptable patient survival rates of approximately 70% at 5 years. Over 70% of recipients with a functioning graft were free from total parenteral nutrition.

Summary
There is an urgent need to establish a nationwide and multinational registry of ITx recipients and patients with intestinal failure in East Asia. An efficient referral system to specialized intestinal rehabilitation and ITx centers and a multidisciplinary team approach is also warranted to provide state-of-the-art treatment for patients desperately waiting for a chance to survive.
Recombination and lineage-specific mutations linked to the emergence of SARS-CoV-2
Authors: Patiño-Galindo Juan Ángel , Filip Ioan , Chowdhury Ratul , Maranas Costas D. , Sorger Peter K. , AlQuraishi Mohammed , Rabadan Raul 
Published: February 2020

AbstractThe emergence of SARS-CoV-2 underscores the need to better understand the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. In the betacoronavirus genus, which also includes SARS-CoV and MERS-CoV, recombination frequently encompasses the Receptor Binding Domain (RBD) of the Spike protein, which, in turn, is responsible for viral binding to host cell receptors. Here, we find evidence of a recombination event in the RBD involving ancestral linages to both SARS-CoV and SARS-CoV-2. Although we cannot specify the recombinant nor the parental strains, likely due to the ancestry of the event and potential undersampling, our statistical analyses in the space of phylogenetic trees support such an ancestral recombination. Consequently, SARS-CoV and SARS-CoV-2 share an RBD sequence that includes two insertions (positions 432-436 and 460-472), as well as the variants 427N and 436Y. Both 427N and 436Y belong to a helix that interacts directly with the human ACE2 (hACE2) receptor. Reconstruction of ancestral states, combined with protein-binding affinity analyses using the physics-based trRosetta algorithm, reveal that the recombination event involving ancestral strains of SARS-CoV and SARS-CoV-2 led to an increased affinity for hACE2 binding, and that alleles 427N and 436Y significantly enhanced affinity as well. Structural modeling indicates that ancestors of SARS-CoV-2 may have acquired the ability to infect humans decades ago. The binding affinity with the human receptor was subsequently boosted in SARS-CoV and SARS-CoV-2 through further mutations in RBD. In sum, we report an ancestral recombination event affecting the RBD of both SARS-CoV and SARS-CoV-2 that was associated with an increased binding affinity to hACE2.ImportanceThis paper addresses critical questions about the origin of the SARS-CoV-2 virus: what are the evolutionary mechanisms that led to the emergence of the virus, and how can we leverage such knowledge to assess the potential of SARS-like viruses to become pandemic strains? In this work, we demonstrate common mechanisms involved in the emergence of human-infecting SARS-like viruses: first, by acquiring a common haplotype in the RBD through recombination, and further, through increased specificity to the human ACE2 receptor through lineage specific mutations. We also show that the ancestors of SARS-CoV-2 already had the potential to infect humans at least a decade ago, suggesting that SARS-like viruses currently circulating in wild animal species constitute a source of potential pandemic re-emergence.
Widespread lateral gene transfer among grasses
Authors: Hibdige Samuel G. S. , Raimondeau Pauline , Christin Pascal-Antoine , Dunning Luke T. 
Published: February 2020

SummaryLateral gene transfer (LGT) has been documented in a broad range of prokaryotes and eukaryotes, and it can promote adaptation. LGT of functional nuclear genes has been reported among some plants, but systematic studies are needed to assess the frequency and facilitators of LGT in the group.We scan the genomes of a diverse set of 17 grass species that span more than 50 million years of divergence and include major crops to identify grass-to-grass protein-coding LGT.We identify LGT in 13 species, with significant variation in the amount each received. Rhizomatous species acquired statistically more genes, probably because this growth habit boosts opportunities for transfer into the germline. In addition, the amount of LGT increases with phylogenetic relatedness, which might reflect genomic compatibility amongst close relatives facilitating successful transfers. However, genetic exchanges among highly divergent species with overlapping distributions also occur, pointing to an additional role of biogeography.Overall, we show that LGT is a widespread phenomenon in grasses, which has moved functional genes across the entire grass family into domesticated and wild species alike. The dynamics of successful LGT appears to be dependent on both opportunity (co-occurrence and rhizomes) and compatibility (phylogenetic distance).
CaptureCompendium: a comprehensive toolkit for 3C analysis
Authors: Telenius Jelena M. , Downes Damien J. , Sergeant Martin , Oudelaar A. Marieke , McGowan Simon , Kerry Jon , Hanssen Lars L.P. , Schwessinger Ron , Eijsbouts Chris Q. , Davies James O.J. , Taylor Stephen , Hughes Jim R. 
Published: February 2020

ABSTRACTDNA folding within nuclei is a highly ordered process, with implications for gene regulation and development. An array of chromosome conformation capture (3C) methods have been developed to investigate how DNA is packaged within nuclei and to interrogate specific interactions. While these methods use different approaches to examine target loci (many-versus-all) or the entire genome (all-versus-all), they all rely on the core principle of endonuclease digestion and proximity-based ligation to re-arrange genomic order to reflect the three-dimensional nuclear conformation. This sequence reorganization creates novel chimeric DNA fragments which require specialist bioinformatic tools to analyze and visualize. Despite this need for specialist bioinformatic skills, the core biological importance of genome folding has seen widespread methodological uptake. To service the needs of experimentalists using the many-versus-all Capture-C family of methods we have developed CaptureCompendium; a toolkit of software to simplify the design, analysis and presentation of 3C experiments.
Structure of the human clamp loader bound to the sliding clamp: a further twist on AAA+ mechanism
Authors: Gaubitz Christl , Liu Xingchen , Magrino Joseph , Stone Nicholas P. , Landeck Jacob , Hedglin Mark , Kelch Brian A. 
Published: February 2020

SUMMARYDNA replication requires the sliding clamp, a ring-shaped protein complex that encircles DNA, where it acts as an essential cofactor for DNA polymerases and other proteins. The sliding clamp needs to be actively opened and installed onto DNA by a clamp loader ATPase of the AAA+ family. The human clamp loader Replication Factor C (RFC) and sliding clamp PCNA are both essential and play critical roles in several diseases. Despite decades of study, no structure of human RFC has been resolved. Here, we report the structure of human RFC bound to PCNA by cryo-EM to an overall resolution of ~3.4 Å. The active sites of RFC are fully bound to ATP analogs, which is expected to induce opening of the sliding clamp. However, we observe the complex in a conformation prior to PCNA opening, with the clamp loader ATPase modules forming an over-twisted spiral that is incapable of binding DNA or hydrolyzing ATP. The autoinhibited conformation observed here has many similarities to a previous yeast RFC:PCNA crystal structure, suggesting that eukaryotic clamp loaders adopt a similar autoinhibited state early on in clamp loading. Our results point to a ‘Limited Change/Induced Fit’ mechanism in which the clamp first opens, followed by DNA binding inducing opening of the loader to release auto-inhibition. The proposed change from an over-twisted to an active conformation reveals a novel regulatory mechanism for AAA+ ATPases. Finally, our structural analysis of disease mutations leads to a mechanistic explanation for the role of RFC in human health.
The Photoconvertible Fluorescent Probe, CaMPARI, Labels Active Neurons in Freely-Moving Intact Adult Fruit Flies
Authors: Edwards Katie A. , Hoppa Michael B. , Bosco Giovanni 
Published: February 2020

AbstractLinking neural circuitry to behavior by mapping active neuronsin vivois a challenge. Both genetically encoded calcium indicators (GECIs) and intermediate early genes (IEGs) have been used to pinpoint active neurons during a stimulus or a behavior but have drawbacks such as limiting the movement of the organism, requiringa prioriknowledge of the active region or having poor temporal resolution. CaMPARI (calcium-modulated photoactivatable ratiometric integrator) was engineered to overcome these spatial-temporal challenges. CaMPARI is a photoconvertible protein that only converts from green to red fluorescence in the presence of high calcium concentration and violet (405 nm) light. This allows the experimenter to precisely mark active neurons within defined temporal windows. The photoconversion can then be quantified by taking the ratio of the red fluorescence to the green. CaMPARI promises the ability to trace active neurons during specific stimulus; however, CaMPARI’s uses in adultDrosophilahave been limited to photoconversion during fly immobilization. Here, we demonstrate a method that allows photoconversion of multiple freely-moving intact adult flies during a stimulus. Flies were placed in a dish with filter paper wet with acetic acid (pH=2) or neutralized acetic acid (pH=7) and exposed to photoconvertible light (60 mW) for 30 min (500 ms on, 200 ms off). Immediately following photoconversion, whole flies were fixed and imaged by confocal microscopy. The red:green ratio was quantified for the DC4 glomerulus, a bundle of neurons expressingIr64a, an ionotropic receptor that senses acids in theDrosophilaantennal lobe. Flies exposed to acetic acid showed 1.3-fold greater photoconversion than flies exposed to neutralized acetic acid. This finding was recapitulated using a more physiological stimulus of apple cider vinegar. These results indicate that CaMPARI can be used to label neurons in intact, freely-moving adult flies and will be useful for identifying the circuitry underlying complex behaviors.