bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized protocols for RNA interference in Macrostomum lignano
Authors: Mouton Stijn , Mougel Alexandra , Ustyantsev Kirill , Dissous Colette , Melnyk Oleg , Berezikov Eugene , Vicogne Jérôme 
Published: February 2024

Abstract
Macrostomum lignano, a marine free-living flatworm, has emerged as a potent invertebrate model in developmental biology for studying stem cells, germline, and regeneration processes. In recent years, many tools have been developed to manipulate this worm and to facilitate genetic modification. RNA interference is currently the most accessible and direct technique to investigate gene functions. It is obtained by soaking worms in artificial seawater containing dsRNA targeting the gene of interest. Although easy to perform, the original protocol calls for daily exchange of dsRNA solutions, usually until phenotypes are observed, which is both time- and cost-consuming. In this work, we have evaluated alternative dsRNA delivery techniques, such as electroporation and osmotic shock, to facilitate the experiments with improved time and cost efficiency. During our investigation to optimize RNAi, we demonstrated that, in the absence of diatoms, regular single soaking in artificial seawater containing dsRNA directly produced in bacteria or synthesized in vitro is, in most cases, sufficient to induce a potent gene knockdown for several days with a single soaking step. Therefore, this new and highly simplified method allows a very significant reduction of dsRNA consumption and lab work. In addition, it enables performing experiments on a larger number of worms at minimal cost.
2ʹ-Hydroxycinnamaldehyde Alleviates Intestinal Inflammation by Attenuating Intestinal Mucosal Barrier Damage Via Directly Inhibiting STAT3
Authors: Chen Meilin , Wei Shuchun , Wu Xiaohan , Xiang Zixuan , Li Xiangyun , He Haodong , Liao Fei , Wang Xiaoli , Zhang Jixiang , Yu Baoping , Dong Weiguo 
Published: February 2024

Abstract

Background
The currently available clinical therapeutic drugs for ulcerative colitis (UC) are considered inadequate owing to certain limitations. There have been reports on the anti-inflammatory effects of 2ʹ-hydroxycinnamaldehyde (HCA). However, whether HCA can improve UC is still unclear. Here, we aimed to investigate the pharmacological effects of HCA on UC and its underlying molecular mechanisms.

Methods
The pharmacological effects of HCA were comprehensively investigated in 2 experimental setups: mice with dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-treated fetal human colon (FHC) cells. Furthermore, the interaction between HCA and signal transducer and activator of transcription 3 (STAT3) was investigated using molecular docking. The FHC cells with STAT3 knockdown or overexpression and mice with intestinal epithelium-specific STAT3 deletion (STAT3ΔIEC) were used to evaluate whether STAT3 mediated the pharmacological effects of HCA.

Results
2ʹ-Hydroxycinnamaldehyde attenuated dysregulated expression of inflammatory cytokines in a dose-dependent manner while increasing the expression of tight junction proteins, reducing the apoptosis of intestinal epithelial cells, and effectively alleviating inflammation both in vivo and in vitro. 2ʹ-Hydroxycinnamaldehyde bound directly to STAT3 and inhibited its activation. The modulation of STAT3 activation levels due to STAT3 knockdown or overexpression influenced the mitigating effects of HCA on colitis. Further analysis indicated that the remission effect of HCA was not observed in STAT3ΔIEC mice, indicating that STAT3 mediated the anti-inflammatory effects of HCA.

Conclusions
We present a novel finding that HCA reduces colitis severity by attenuating intestinal mucosal barrier damage via STAT3. This discovery holds promise as a potential new strategy to alleviate UC.
M-estimation for common epidemiological measures: introduction and applied examples
Authors: Ross Rachael K , Zivich Paul N , Stringer Jeffrey S A , Cole Stephen R 
Published: February 2024

Abstract
M-estimation is a statistical procedure that is particularly advantageous for some comon epidemiological analyses, including approaches to estimate an adjusted marginal risk contrast (i.e. inverse probability weighting and g-computation) and data fusion. In such settings, maximum likelihood variance estimates are not consistent. Thus, epidemiologists often resort to bootstrap to estimate the variance. In contrast, M-estimation allows for consistent variance estimates in these settings without requiring the computational complexity of the bootstrap. In this paper, we introduce M-estimation and provide four illustrative examples of implementation along with software code in multiple languages. M-estimation is a flexible and computationally efficient estimation procedure that is a powerful addition to the epidemiologist’s toolbox.
The Burden of Hepatitis A Outbreaks in the United States: Health Outcomes, Economic Costs, and Management Strategies
Authors: Horn Emily K , Herrera-Restrepo Oscar , Acosta Anna M , Simon Alyssa , Jackson Bianca , Lucas Eleanor 
Published: February 2024

Abstract

Background
Hepatitis A (HepA) vaccines are recommended for US adults at risk of HepA. Ongoing United States (US) HepA outbreaks since 2016 have primarily spread person-to-person, especially among at-risk groups. We investigated the health outcomes, economic burden, and outbreak management considerations associated with HepA outbreaks from 2016 onwards.

Methods
A systematic literature review was conducted to assess HepA outbreak-associated health outcomes, health care resource utilization (HCRU), and economic burden. A targeted literature review evaluated HepA outbreak management considerations.

Results
Across 33 studies reporting on HepA outbreak-associated health outcomes/HCRU, frequently reported HepA-related morbidities included acute liver failure/injury (n = 6 studies of 33 studies) and liver transplantation (n = 5 of 33); reported case fatality rates ranged from 0% to 10.8%. Hospitalization rates reported in studies investigating person-to-person outbreaks ranged from 41.6% to 84.8%. Ten studies reported on outbreak-associated economic burden, with a national study reporting an average cost of over $16 000 per hospitalization. Thirty-four studies reported on outbreak management; challenges included difficulty reaching at-risk groups and vaccination distrust. Successes included targeted interventions and increasing public awareness.

Conclusions
This review indicates a considerable clinical and economic burden of ongoing US HepA outbreaks. Targeted prevention strategies and increased public awareness and vaccination coverage are needed to reduce HepA burden and prevent future outbreaks.
Interventionism and Intelligibility: Why Depression Is Not (Always) a Brain Disease
Authors: Gibson Quinn Hiroshi 
Published: February 2024

Abstract
Major depressive disorder (MDD) is a serious condition with a large disease burden. It is often claimed that MDD is a “brain disease.” What would it mean for MDD to be a brain disease? I argue that the best interpretation of this claim is as offering a substantive empirical hypothesis about the causes of the syndrome of depression. This syndrome-causal conception of disease, combined with the idea that MDD is a disease of the brain, commits the brain disease conception of MDD to the claim that brain dysfunction causes the symptoms of MDD. I argue that this consequence of the brain disease conception of MDD is false. It incorrectly rules out genuine instances of content-sensitive causation between adverse conditions in the world and the characteristic symptoms of MDD. Empirical evidence shows that the major causes of depression are genuinely psychological causes of the symptoms of MDD. This rules out, in many cases, the “brute” causation required by the brain disease conception. The existence of cases of MDD with non-brute causes supports the reinstatement of the old nosological distinction between endogenous and exogenous depression.
Testing unit root non-stationarity in the presence of missing data in univariate time series of mobile health studies
Authors: Fowler Charlotte , Cai Xiaoxuan , Baker Justin T , Onnela Jukka-Pekka , Valeri Linda 
Published: February 2024

Abstract
The use of digital devices to collect data in mobile health studies introduces a novel application of time series methods, with the constraint of potential data missing at random or missing not at random (MNAR). In time-series analysis, testing for stationarity is an important preliminary step to inform appropriate subsequent analyses. The Dickey–Fuller test evaluates the null hypothesis of unit root non-stationarity, under no missing data. Beyond recommendations under data missing completely at random for complete case analysis or last observation carry forward imputation, researchers have not extended unit root non-stationarity testing to more complex missing data mechanisms. Multiple imputation with chained equations, Kalman smoothing imputation, and linear interpolation have also been used for time-series data, however such methods impose constraints on the autocorrelation structure and impact unit root testing. We propose maximum likelihood estimation and multiple imputation using state space model approaches to adapt the augmented Dickey–Fuller test to a context with missing data. We further develop sensitivity analyses to examine the impact of MNAR data. We evaluate the performance of existing and proposed methods across missing mechanisms in extensive simulations and in their application to a multi-year smartphone study of bipolar patients.
A toy model for gas sloshing in galaxy clusters
Authors: Roediger E , Vaezzadeh I , Nulsen P 
Published: February 2024

ABSTRACT
We apply a toy model based on ‘pendulum waves’ to gas sloshing in galaxy clusters. Starting with a galaxy cluster potential filled with a hydrostatic intracluster medium (ICM), we perturb all ICM by an initial small, unidirectional velocity, i.e. an instantaneous kick. Consequently, each parcel of ICM will oscillate due to buoyancy with its local Brunt–Väisälä (BV) period, which we show to be approximately proportional to the cluster radius. The oscillation of gas parcels at different radii with different periods leads to a characteristic, outward-moving coherent pattern of local compressions and rarefactions; the former form the sloshing cold fronts (SCFs). Our model predicts that SCFs (i) appear in the cluster centre first, (ii) move outwards on several Gyr time-scales, (iii) form a staggered pattern on opposite sides of a given cluster, (iv) each move outwards with approximately constant speed; and that (v) inner SCFs form discontinuities more easily than outer ones. These features are well known from idealized (magneto)hydrodynamic simulations of cluster sloshing. We perform comparison hydrodynamic + N-body simulations where sloshing is triggered either by an instantaneous kick or a minor merger. Sloshing in these simulations qualitatively behaves as predicted by the toy model. However, the toy model somewhat overpredicts the speed of sloshing fronts, and does not predict that inner SCFs emerge with a delay compared to outer ones. In light of this, we identify the outermost cold front, which may be a ‘failed’ SCF, as the best tracer of the age of the merger that set a cluster sloshing.
Slow body magnetohydrodynamic waves in solar photospheric flux tubes with density inhomogeneity
Authors: Asiri F , Ballai I , Fedun V , Verth G , Ruzheinikov S N , Albidah A B 
Published: February 2024

ABSTRACT
Pores and sunspots are ideal environments for the propagation of guided magnetohydrodynamic (MHD) waves. However, modelling such photospheric waveguides with varying background quantities such as plasma density and magnetic field has thus far been very limited. Such modelling is required to correctly interpret MHD waves observed in pores and sunspots with resolved inhomogeneities such as light bridges and umbral dots. This study will investigate the propagation characteristics and the spatial structure of slow body MHD modes in a magnetic flux tube with a circular cross-section with inhomogeneous equilibrium density distribution under solar photospheric conditions in the short wavelength limit. For simplicity, the equilibrium density profile is taken to have a circular density enhancement or depletion. The advantage of this is that the strength, size, and position of the density inhomogeneity can be easily changed. Calculating the eigenfrequencies and eigenfunctions of the slow body modes is addressed numerically with use of the Fourier–Chebyshev Spectral method. The radial and azimuthal variation of eigenfunctions is obtained by solving a Helmholtz-type partial differential equation with Dirichlet boundary conditions. The inhomogeneous equilibrium density profile results in modified eigenvalues and eigenvectors. It was found that a localized density inhomogeneity leads to a decrease in the eigenvalues and the spatial structure of modes ceases to be a global harmonic oscillation, as the modes migrate towards regions of lower density. Comparing the homogeneous case and the cases corresponding to depleted density enhancement, the dimensionless phase speed undergoes a significant drop in its value (at least 40 per cent).
Convective mixing: the formation channel of Li-rich giants
Authors: Li Xue-Feng , Shi Jian-Rong , Li Yan , Yan Hong-Liang , Zhang Jing-Hua 
Published: February 2024

ABSTRACT
Increasing observed data indicate that part of giants has abnormally high lithium (Li) inside their surface, and their proportion is around 1 per cent. Instead of pursuing the feasible mechanisms for extra Li enrichment, we focus on how to inhibit Li depletion from the main-sequence phase of giants. With this in mind, we find that convective mixing is capable of achieving this goal and forming Li-rich giants, which is mainly attributed to the convection model with the convective boundary defined by the Ledoux criterion. Another factor in the formation of Li-rich giants in our convection models is related to the Li abundances of their progenitors. If the Li abundances of the progenitors exceed the meteoritic value ($\rm 3.3\ dex$), then the majority of giants will be rich in Li. This is the general pattern of stellar Li abundance evolution without factoring in extra Li depletion. We propose that other Li depletion processes should also be adopted in the future, as they may be the key to the 1 per cent puzzle.
Chemical modification patterns for microRNA therapeutic mimics: a structure-activity relationship (SAR) case-study on miR-200c
Authors: Garreau Marion , Weidner Julie , Hamilton Russell , Kolosionek Ewa , Toki Naoko , Stavenhagen Kathrin , Paris Clément , Bonetti Alessandro , Czechtizky Werngard , Gnerlich Felix , Rydzik Anna 
Published: February 2024

Abstract
microRNA (miRNA) mimics are an emerging class of oligonucleotide therapeutics, with a few compounds already in clinical stages. Synthetic miRNAs are able to restore downregulated levels of intrinsic miRNAs, allowing for parallel regulation of multiple genes involved in a particular disease. In this work, we examined the influence of chemical modifications patterns in miR-200c mimics, assessing the regulation of a selection of target messenger RNAs (mRNA) and, subsequently, of the whole transcriptome in A549 cells. We have probed 37 mimics and provided an initial set of instructions for designing miRNA mimics with potency and selectivity similar to an unmodified miRNA duplex. Additionally, we have examined the stability of selected mimics in serum. Finally, the selected two modification patterns were translated to two other miRNAs, miR-34a and miR-155. To differing degrees, these designs acted on target mRNAs in a similar manner to the unmodified mimic. Here, for the first time, we describe a structured overview of ‘miRNA mimics modification templates’ that are chemically stabilised and optimised for use in an in vitro set up and highlight the need of further sequence specific optimization when mimics are to be used beyond in vitro tool experiments.
Hepatitis C and Cigarette Smoking Behavior: Themes From Focus Groups
Authors: Cohen Julia F , Ward Kathleen M , Gittleman Jennifer , Perez Esther , Pia Tyler , Shuter Jonathan , Weinberger Andrea H , Sulkowski Mark 
Published: February 2024

Abstract

Introduction
People with chronic hepatitis C virus (HCV; PWHC) use cigarettes at a much higher prevalence than other individuals, and smoking can exacerbate the harms specifically related to HCV (eg, hepatocellular carcinoma). Little is known about factors related to cigarette use among PWHC.

Aims and Methods
This study examined focus group data to explore beliefs and behaviors related to cigarette use among PWHC. Qualitative data from two focus groups of PWHC reporting current cigarette smoking (n = 15, 60% male) were collected using a semi-structured interview guide. Participants were asked about reasons for smoking, barriers to quitting smoking, and the relationship of HCV to smoking. Focus groups were transcribed verbatim and coded in NVivo 12. Four coders examined themes that arose in the focus groups. Common themes are described and supported with quotes.

Results
Reasons for smoking included addiction to cigarettes, stress, substituting cigarettes for other drugs, and social norms, while reasons for quitting included health and being free from the use of all drugs. Barriers to quitting included concerns about coping with stress, weight gain, and having a lack of support for and education about quitting. Many participants believed there was a link between smoking and HCV and discussed smoking in relation to the stress of an HCV diagnosis.

Conclusions
Participants identified both HCV-related and non-HCV-related aspects of cigarette smoking and cessation-related behaviors that could be targeted in cessation treatment. More research is needed to identify the best treatment approaches that reduce the significant medical consequences of cigarette use among PWHC.

Implications
People with chronic hepatitis C virus (HCV; PWHC) smoke cigarettes at a high prevalence, yet little is known about their smoking behaviors. Moreover, there are no cessation treatments targeting PWHC. This is the first study to collect focus group data from PWHC who smoke in order to identify reasons for cigarette use (HCV-related and non-HCV-related), and motivators and barriers to quitting cigarettes. PWHC reports using cigarettes to cope with the stress of an HCV diagnosis and to celebrate HCV cure. These findings suggest there are specific times during the HCV care continuum where providers can aid with cessation efforts.
Postcumulus Processes Recorded in Whole-Rock Geochemistry: a Case Study from the Mirabela Layered Intrusion, Brazil
Authors: Barnes Stephen J , Williams Morgan 
Published: February 2024

Abstract
According to the ‘trapped liquid’ paradigm, whole-rock chemical compositions of cumulate rocks in layered intrusions can be represented as closed-system multicomponent mixtures of the cumulus phases and the liquids from which they crystallised. Alternative open-system models for cumulate solidification assert that intercumulus liquid is continuously mobile as a result of compaction of crystal mushes. In the closed-system models, all excluded elements, i.e. those incompatible in the cumulus phases, should be correlated with one another, whereas in open systems the more incompatible elements should be decoupled from the more compatible ones and correlations should be poor. These alternative hypotheses are tested using a database of &gt;63 000 whole-rock analyses of mostly ultramafic cumulates from a single package of layers across the entire width of the Mirabela layered intrusion, a 2.5-km-wide by &gt;2-km-thick intrusion with Great Dyke-like stratigraphy. Variably compatible elements Al, Na, Ti and P are found to show strong correlations with one other in olivine-pyroxene cumulates across the spectrum from mesocumulate to orthocumulate rocks, where drill-core sample intervals are composited over 3 m; weaker correlations are found over 1-m sample intervals. The closed-system trapped liquid model is robust for this suite of rocks at the scale of 3-m lengths of drill core (~1 kg of sample). Furthermore, a very smooth and symmetrical variation is observed from dominantly ad- to mesocumulate rocks in the geometrical centre of the intrusion towards orthocumulates at both margins, attributable to increase in cooling rate towards the margins. The most adcumulate rocks are gabbronorites at the base of the mafic sequence in the centre of the intrusion. There is no corresponding decrease in layer thickness towards the centre that would be predicted by a compaction model. The only incompatible element showing partial decoupling is K, which appears to have been mobile at a very late stage, probably in an aqueous fluid phase. There is no evidence for mobilisation of platinum group elements or other chalcophile elements by this fluid despite the presence of disseminated sulfide throughout the sampled interval.
Metamorphism of Dolomitic and Magnesitic Rocks in Collisional Orogens and Implications for Orogenic CO2 Degassing
Authors: Tamang Shashi , Groppo Chiara , Girault Frédéric , Perrier Frédéric , Rolfo Franco 
Published: February 2024

Abstract
Carbonate-bearing sediments, containing calcite, dolomite or magnesite as major carbonate components, are important constituents of sedimentary sequences deposited on passive margins through Earth’s history. When involved in collisional orogenic processes, these sediments are metamorphosed at variable temperatures and pressures, and undergo decarbonation reactions. While the orogenic metamorphism of some of these lithologies (i.e. impure limestones and dolostones, marls sensu stricto and calcareous pelites) is relatively well understood, very little is known about the metamorphic evolution and decarbonation history of mixed carbonate–silicate rocks in which either dolomite or magnesite is the dominant carbonate component.
Here we present the results of a petrologic study of representative samples of metasediments from Central Nepal, derived from Proterozoic dolomitic and magnesitic protoliths metamorphosed during the Himalayan orogeny. The main metamorphic assemblages developed in sediments originally containing different amounts of dolomite or magnesite are characterised in detail. Forward thermodynamic modelling applied to seven samples allows constraints to be placed on (i) the main decarbonation reactions, (ii) the P–T conditions under which these reactions took place, (iii) the composition of the fluids, and (iv) the amounts of CO2 released.
We conclude that the CO2 productivity of dolomitic and magnesitic pelites and marls originally containing 15–40% carbonate is significant (&gt;5.5 ± 1.0 CO2 wt% and up to 10.5 ± 1.5 CO2 wt%), whereas for carbonate contents above 60–70%, CO2 productivity is negligible unless aqueous fluids infiltrate from the outside and trigger decarbonation reactions. Since the dolomitic and magnesitic protoliths are significantly abundant in the sedimentary sequences involved in the still active Himalayan orogen, the decarbonation processes described here could contribute to the diffuse CO2 degassing currently observed at the surface. Furthermore, we propose for the first time that the peculiar magnesium-rich assemblages investigated in this study may derive from evaporitic protoliths, and that the whole Upper Lesser Himalayan Sequence may therefore represent the metamorphic product of a Proterozoic sequence consisting of alternating layers of carbonatic, evaporitic and pelitic sediments.