bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonpharmacological interventions for the management of fatigue and constitutional symptoms in Sjögren’s syndrome
Authors: Hackett Katie L. , Cartner Helen 
Published: May 2021

Abstract
Current treatments for Sjögren’s syndrome (SS) are limited. Pharmacological treatments tend to focus on topical treatments for dryness or oral muscarinic agonists which increase tear production and salivary flow. National treatment guidelines for primary SS incorporating available published evidence and expert opinion include recommendations for specific pharmacological topical and systemic treatments. However, despite the availability of such treatments, SS patients still experience symptoms, difficulties performing their daily activities, and reduced quality of life. This chapter explores specific ways nonpharmacological support for patients with primary SS might be delivered. These include the provision of information and patient education, as well as specific symptom management support for anxiety, sleep disturbances, pain, discomfort, low mood, and anxiety. Possible modes of delivering interventions and consideration of the differing levels of support which are required for different patients are also discussed.
Juvenile- and young adult–onset Sjögren’s syndrome
Authors: Renton William D. , Price Elizabeth J. , Ramanan A.V. 
Published: May 2021

Abstract
Sjögren’s syndrome (SS) is very rare in teenagers and there are only anecdotal reports world-wide of its occurrence in prepubertal children. Paediatric cohort studies have demonstrated that approximately half of patients with Sjögren’s syndrome (SS) have primary disease. As with adults, secondary SS is most commonly associated with systemic lupus erythematosus, although cases have also been reported in patients with juvenile idiopathic arthritis, mixed connective tissue disease, and other autoimmune conditions. The condition is almost certainly underdiagnosed. Children and young adults rarely complain of dryness and usually present with parotid gland swelling and systemic disease. Clinical manifestations, diagnosis, and management are all discussed in this chapter.
Mimics of Sjögren’s syndrome
Authors: Sutcliffe Nurhan 
Published: May 2021

Abstract
Systemic diseases, which affect salivary and lacrimal glands, can cause dry eyes and mouth and swelling of the affected glands and may present in a similar way to SS. There may also be overlapping extra-glandular, laboratory, and imaging features, which can pose a diagnostic challenge. Certain diseases affecting salivary and lacrimal glands such as sarcoidosis, IgG4-related disease, chronic hepatitis C virus, HIV infections, and graft-versus-host disease can mimic Sjögren’s syndrome, usually via a process of similar inflammation of affected glands. This chapter will focus on these diseases. When evaluating a patient with suspected primary Sjögren’s syndrome it is important to rule out its differential diagnoses. Biopsy of the major or minor salivary gland or of the lacrimal glands may sometimes be needed to reach a final diagnosis.
Double common envelope jets supernovae (CEJSNe) by triple-star systems
Authors: Soker Noam 
Published: May 2021

ABSTRACT
I propose a new type of common envelope jets supernova (CEJSN) events where instead of a single neutron star (NS; or a black hole; BH) a tight binary system of an NS and a main-sequence star enters a common envelope evolution (CEE) with a red supergiant. The NS and the main-sequence star of the tight binary system merge inside the red supergiant envelope and enter a CEE of their own. The NS accretes some mass through an accretion disc and launches jets that explodes the main-sequence star. I estimate that the two jets that the NS launches at this phase carry an energy of $\approx 10^{52} {~\rm erg}$, about the same order of magnitude as the energy that the jets will carry when the NS or its BH remnant will enter the core in a later phase. For that, I term the entire event a double CEJSN. The outcome of the double CEJSN is a very long, months to years, and very energetic event, a total energy of $\approx 10^{52} \!-\! 10^{53} {~\rm erg}$, that will be observationally classified as a peculiar superenergetic event. I crudely estimate that new transient surveys should detect about one CEJSN event from a triple-star system per year.
Submillimetre observations of the two-component magnetic field in M82
Authors: Pattle Kate , Gear Walter , Redman Matt , Smith Matthew W L , Greaves Jane 
Published: May 2021

ABSTRACT
We observed the starburst galaxy M82 in 850 µm polarized light with the POL-2 polarimeter on the James Clerk Maxwell Telescope (JCMT). We interpret our observed polarization geometry as tracing a two-component magnetic field: a poloidal component aligned with the galactic ‘superwind’, extending to a height ∼350 pc above and below the central bar; and a spiral-arm-aligned, or possibly toroidal, component in the plane of the galaxy, which dominates the 850 µm polarized light distribution at galactocentric radii ≳2 kpc. Comparison of our results with recent High-resolution Airborne Wideband Camera Plus (HAWC+) measurements of the field in the dust entrained by the M82 superwind suggests that the superwind breaks out from the central starburst at ∼350 pc above the plane of the galaxy.
Locally Adaptive Inversions Modulate Genetic Variation at Different Geographic Scales in a Seaweed Fly
Authors: Mérot Claire , Berdan Emma L , Cayuela Hugo , Djambazian Haig , Ferchaud Anne-Laure , Laporte Martin , Normandeau Eric , Ragoussis Jiannis , Wellenreuther Maren , Bernatchez Louis 
Published: May 2021

AbstractAcross a species range, multiple sources of environmental heterogeneity, at both small and large scales, create complex landscapes of selection, which may challenge adaptation, particularly when gene flow is high. One key to multidimensional adaptation may reside in the heterogeneity of recombination along the genome. Structural variants, like chromosomal inversions, reduce recombination, increasing linkage disequilibrium among loci at a potentially massive scale. In this study, we examined how chromosomal inversions shape genetic variation across a species range and ask how their contribution to adaptation in the face of gene flow varies across geographic scales. We sampled the seaweed fly Coelopa frigida along a bioclimatic gradient stretching across 10° of latitude, a salinity gradient, and a range of heterogeneous, patchy habitats. We generated a chromosome-level genome assembly to analyze 1,446 low-coverage whole genomes collected along those gradients. We found several large nonrecombining genomic regions, including putative inversions. In contrast to the collinear regions, inversions and low-recombining regions differentiated populations more strongly, either along an ecogeographic cline or at a fine-grained scale. These genomic regions were associated with environmental factors and adaptive phenotypes, albeit with contrasting patterns. Altogether, our results highlight the importance of recombination in shaping adaptation to environmental heterogeneity at local and large scales.
Unravelling the mechanisms of Type 1A topoisomerases using single-molecule approaches
Authors: Spakman Dian , Bakx Julia A M , Biebricher Andreas S , Peterman Erwin J G , Wuite Gijs J L , King Graeme A 
Published: May 2021

AbstractTopoisomerases are essential enzymes that regulate DNA topology. Type 1A family topoisomerases are found in nearly all living organisms and are unique in that they require single-stranded (ss)DNA for activity. These enzymes are vital for maintaining supercoiling homeostasis and resolving DNA entanglements generated during DNA replication and repair. While the catalytic cycle of Type 1A topoisomerases has been long-known to involve an enzyme-bridged ssDNA gate that allows strand passage, a deeper mechanistic understanding of these enzymes has only recently begun to emerge. This knowledge has been greatly enhanced through the combination of biochemical studies and increasingly sophisticated single-molecule assays based on magnetic tweezers, optical tweezers, atomic force microscopy and Förster resonance energy transfer. In this review, we discuss how single-molecule assays have advanced our understanding of the gate opening dynamics and strand-passage mechanisms of Type 1A topoisomerases, as well as the interplay of Type 1A topoisomerases with partner proteins, such as RecQ-family helicases. We also highlight how these assays have shed new light on the likely functional roles of Type 1A topoisomerases in vivo and discuss recent developments in single-molecule technologies that could be applied to further enhance our understanding of these essential enzymes.
Marker-free quantification of repair pathway utilization at Cas9-induced double-strand breaks
Authors: Feng Wanjuan , Simpson Dennis A , Cho Jang-Eun , Carvajal-Garcia Juan , Smith Chelsea M , Headley Kathryn M , Hathaway Nate , Ramsden Dale A , Gupta Gaorav P 
Published: May 2021

Abstract
Genome integrity and genome engineering require efficient repair of DNA double-strand breaks (DSBs) by non-homologous end joining (NHEJ), homologous recombination (HR), or alternative end-joining pathways. Here we describe two complementary methods for marker-free quantification of DSB repair pathway utilization at Cas9-targeted chromosomal DSBs in mammalian cells. The first assay features the analysis of amplicon next-generation sequencing data using ScarMapper, an iterative break-associated alignment algorithm to classify individual repair products based on deletion size, microhomology usage, and insertions. The second assay uses repair pathway-specific droplet digital PCR assays (‘PathSig-dPCR’) for absolute quantification of signature DSB repair outcomes. We show that ScarMapper and PathSig-dPCR enable comprehensive assessment of repair pathway utilization in different cell models, after a variety of experimental perturbations. We use these assays to measure the differential impact of DNA end resection on NHEJ, HR and polymerase theta-mediated end joining (TMEJ) repair. These approaches are adaptable to any cellular model system and genomic locus where Cas9-mediated targeting is feasible. Thus, ScarMapper and PathSig-dPCR allow for systematic fate mapping of a targeted DSB with facile and accurate quantification of DSB repair pathway choice at endogenous chromosomal loci.
Preselector.uni-jena.de: optimize your cloning—a resource for identifying restriction enzymes for preselection reactions
Authors: Gühmann Martin , Reuter Stefanie , Hartung Jan , Mrowka Ralf 
Published: May 2021

Abstract
Preselection digests are a common strategy to reduce the background in the ligation step of molecular cloning. However, choosing fitting restriction enzymes by hand is not trivial and may lead to errors, potentially costing a lot of time and work. We therefore created preselector.uni-jena.de (https://preselector.uni-jena.de/), a free online tool to find such restriction enzymes. The tool uses regular expressions to find recognition sites of restriction enzymes in the DNA sequences provided by the user. This new tool compares the sets of restriction sites and reports the enzymes that cut one sequence but not the other sequences to the user. These enzymes are then the ones suitable for a preselection digest. Thus, preselector.uni-jena.de is a fast, reliable, and free-to-use tool to help researchers designing preselection digestion strategies for their cloning.
DeepFun: a deep learning sequence-based model to decipher non-coding variant effect in a tissue- and cell type-specific manner
Authors: Pei Guangsheng , Hu Ruifeng , Jia Peilin , Zhao Zhongming 
Published: May 2021

AbstractMore than 90% of the genetic variants identified from genome-wide association studies (GWAS) are located in non-coding regions of the human genome. Here, we present a user-friendly web server, DeepFun (https://bioinfo.uth.edu/deepfun/), to assess the functional activity of non-coding genetic variants. This new server is built on a convolutional neural network (CNN) framework that has been extensively evaluated. Specifically, we collected chromatin profiles from ENCODE and Roadmap projects to construct the feature space, including 1548 DNase I accessibility, 1536 histone mark, and 4795 transcription factor binding profiles covering 225 tissues or cell types. With such comprehensive epigenomics annotations, DeepFun expands the functionality of existing non-coding variant prioritizing tools to provide a more specific functional assessment on non-coding variants in a tissue- and cell type-specific manner. By using the datasets from various GWAS studies, we conducted independent validations and demonstrated the functions of the DeepFun web server in predicting the effect of a non-coding variant in a specific tissue or cell type, as well as visualizing the potential motifs in the region around variants. We expect our server will be widely used in genetics, functional genomics, and disease studies.
The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination
Authors: Ramos-Morales Elizabeth , Bayam Efil , Del-Pozo-Rodríguez Jordi , Salinas-Giegé Thalia , Marek Martin , Tilly Peggy , Wolff Philippe , Troesch Edouard , Ennifar Eric , Drouard Laurence , Godin Juliette D , Romier Christophe 
Published: May 2021

Abstract
Post-transcriptional modification of tRNA wobble adenosine into inosine is crucial for decoding multiple mRNA codons by a single tRNA. The eukaryotic wobble adenosine-to-inosine modification is catalysed by the ADAT (ADAT2/ADAT3) complex that modifies up to eight tRNAs, requiring a full tRNA for activity. Yet, ADAT catalytic mechanism and its implication in neurodevelopmental disorders remain poorly understood. Here, we have characterized mouse ADAT and provide the molecular basis for tRNAs deamination by ADAT2 as well as ADAT3 inactivation by loss of catalytic and tRNA-binding determinants. We show that tRNA binding and deamination can vary depending on the cognate tRNA but absolutely rely on the eukaryote-specific ADAT3 N-terminal domain. This domain can rotate with respect to the ADAT catalytic domain to present and position the tRNA anticodon-stem-loop correctly in ADAT2 active site. A founder mutation in the ADAT3 N-terminal domain, which causes intellectual disability, does not affect tRNA binding despite the structural changes it induces but most likely hinders optimal presentation of the tRNA anticodon-stem-loop to ADAT2.
The Flavor Train: The Nature and Extent of Flavored Cigarettes in Low- and Middle-Income Countries
Authors: Cohen Joanna E , Welding Kevin , Erinoso Olufemi , Saraf Sejal , Iacobelli Michael , Smith Katherine C 
Published: May 2021

Abstract

Introduction
Flavors and depictions of flavors are attractive and facilitate initiation and use of tobacco products. However, little is known about the types of flavored products on the market, particularly in low- and middle-income countries. We describe the nature and extent of flavored cigarettes sold in nine low- and middle-income countries from four of the six World Health Organization (WHO) regions.

Aims and Methods
We employed a systematic protocol to purchase unique cigarette packs in Bangladesh, Brazil, China, India, Indonesia, Philippines, Russia, Thailand, and Vietnam. Packs were double coded for flavor descriptors and imagery using a standard codebook. Frequencies and crosstabs were conducted to examine the proportion of packs with flavor descriptors and/or flavor imagery, and flavor capsules, by country and by major manufacturer.

Results
Overall, 15.4% of the country-unique cigarette packs had flavor descriptors and/or imagery, representing a variety of flavors: menthol or mint (8.2%), “concept” descriptors (3.5%) (eg, Fusion blast), fruit or citrus (3.3%), beverages (1.4%), and others (1.4%). Flavor was mostly communicated using descriptors (15.2%), with flavor imagery being less common (2.2%). Flavor capsules were prevalent (6.2%), with almost half having “concept” descriptors. All major tobacco companies produced cigarettes with flavors, and with capsules.

Conclusions
A range of flavored cigarettes remain on the market in the low- and middle-income countries with the greatest number of smokers. This finding is particularly concerning given the appeal of flavored cigarettes among youth and their potential to circumvent country bans on flavored tobacco products if those laws are not sufficiently comprehensive. Laws addressing flavored tobacco products need to account for flavor capsules and concept descriptors.

Implications
While a number of countries have restricted flavors in tobacco products to reduce their appeal and attractiveness, a range of flavors continue to be on the market in low- and middle-income countries, putting people in these countries at increased risk for tobacco use and subsequent tobacco-caused death and disease. The presence of capsules and concept descriptors is particularly concerning given their appeal among youth and their potential to circumvent country bans on flavored tobacco products if those laws are not sufficiently comprehensive.
Aquaporin family lactic acid channel NIP2;1 promotes plant survival under low oxygen stress in Arabidopsis
Authors: Beamer Zachary G , Routray Pratyush , Choi Won-Gyu , Spangler Margaret K , Lokdarshi Ansul , Roberts Daniel M 
Published: May 2021

AbstractUnder anaerobic stress, Arabidopsis thaliana induces the expression of a collection of core hypoxia genes that encode proteins for an adaptive response. Among these genes is NIP2;1, which encodes a member of the “Nodulin 26-like Intrinsic Protein” (NIP) subgroup of the aquaporin superfamily of membrane channel proteins. NIP2;1 expression is limited to the “anoxia core” region of the root stele under normal growth conditions, but shows substantial induction (up to 1,000-fold by 2–4 h of hypoxia) by low oxygen stress, and accumulation in all root tissues. During hypoxia, NIP2;1-GFP accumulates predominantly on the plasma membrane by 2 h, is distributed between the plasma and internal membranes during sustained hypoxia, and remains elevated in root tissues through 4 h of reoxygenation recovery. In response to hypoxia challenge, T-DNA insertion mutant nip2;1 plants exhibit elevated lactic acid within root tissues, reduced efflux of lactic acid, and reduced acidification of the external medium compared to wild-type plants. Previous biochemical evidence demonstrates that NIP2;1 has lactic acid channel activity, and our work supports the hypothesis that NIP2;1 prevents lactic acid toxicity by facilitating release of cellular lactic acid from the cytosol to the apoplast, supporting eventual efflux to the rhizosphere. In evidence, nip2;1 plants demonstrate poorer survival during argon-induced hypoxia stress. Expressions of the ethanolic fermentation transcript Alcohol Dehydrogenase1 and the core hypoxia-induced transcript Alanine Aminotransferase1 are elevated in nip2;1, and expression of the Glycolate Oxidase3 transcript is reduced, suggesting NIP2;1 lactic acid efflux regulates other pyruvate and lactate metabolism pathways.
Framing action to reduce health inequalities: what is argued for through use of the ‘upstream–downstream’ metaphor?
Authors: McMahon Naoimh E 
Published: May 2021

Abstract

Background
Public health insights struggle to compete with dominant ideas which frame health inequalities as a problem of individual behaviour. There is consequently a need to critically reflect upon and question the effectiveness of different strategies for framing and communicating key insights. Taking the example of the ‘upstream–downstream’ metaphor, this literature review contributes to a necessary first step by asking what exactly is being argued for through its use.

Methods
An iterative search strategy was used to identify peer-reviewed articles which could contribute to the review question. A discourse analysis framework informed data extraction and synthesis of 24 articles. Articles were subsequently categorized into groups which reflected the different uses of the metaphor identified.

Results
All authors used the metaphor to promote a particular causal understanding of health inequalities, leading some to recommend policies and programmes, and others to focus on implementation processes. This seemingly simple metaphor has evolved beyond differentiating ‘upstream’ from ‘downstream’ determinants, to communicate an ambitious politically engaged agenda for change.

Conclusions
The metaphor is not without its critics and in light of the complexity of the arguments encapsulated in its use, work is needed to establish if it can, and does, resonate as intended with wider audiences.
COVID-19 deaths in the USA: Benford’s law and under-reporting
Authors: Campolieti Michele 
Published: May 2021

Abstract

Background
I use Benford’s law to assess whether there is misreporting of coronavirus disease of 2019 (COVID-19) deaths in the USA.

Methods
I use three statistics to determine whether the reported deaths for US states are consistent with Benford’s law, where the probability of smaller digits is greater than the probability of larger digits.

Results
My findings indicate that there is under-reporting of COVID-19 deaths in the USA, although the evidence for and the extent of under-reporting does depend on the statistic one uses to assess conformity with Benford’s law.

Conclusions
Benford’s law is a useful diagnostic tool for verifying data and can be used before a more detailed audit or resource intensive investigation.
Investigating Patient Acceptability of Stratified Medicine for Schizophrenia: A Mixed Methods Study
Authors: Jilka Sagar , Odoi Clarissa Mary , Meran Sazan , MacCabe James H , Wykes Til 
Published: May 2021

Abstract

Background
Health services have advocated a stratified medicine approach in mental health, but little is known about whether service users would accept this approach.

Aims
To explore service users’ views of the acceptability of stratified medicine for treatment-resistant schizophrenia compared to the traditional “trial-and-error” approach.

Methods
A mixed methods observational study that explored questionnaire responses on acceptability and whether these responses were affected by demographic or clinical variables. We also investigated whether treatment responsiveness or experience of invasive tests (brain scans and blood tests) affected participants’ responses. Questionnaire generated qualitative data were analyzed thematically. Participants (N108) were aged 18–65, had a diagnosis of schizophrenia, and were adherent to antipsychotic medication.

Results
Acceptability of a stratified approach was high, even after participants had experienced invasive tests. Most rated it as safer (62% vs 43%; P &lt; .01 [CI: −1.69 to 2.08]), less risky (77% vs 44%; P &lt; .01 [CI: −1.75 to 1.10]), and less painful (90% vs 73%; P &lt; 0.01 [CI: −0.84 to 0.5]) and this was not affected by treatment responsiveness or test experience. Although not statistically significant, treatment nonresponders were more willing to undergo invasive tests. Qualitatively, all participants raised concerns about the risks, discomfort, and potential side effects associated with the invasive tests.

Conclusions
Service users were positive about a stratified approach for choosing treatments but were wary of devolving clinical decisions to purely data-driven algorithms. These results reinforce the value of service user perspectives in the development and evaluation of novel treatment approaches.