bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic–epigenetic interplay in the determination of plant 3D genome organization
Authors: He Xiaoning , Dias Lopes Chloé , Pereyra-Bistrain Leonardo I , Huang Ying , An Jing , Chaouche Rim Brik , Zalzalé Hugo , Wang Qingyi , Ma Xing , Antunez-Sanchez Javier , Bergounioux Catherine , Piquerez Sophie , Fragkostefanakis Sotirios , Zhang Yijing , Zheng Shaojian , Crespi Martin , Mahfouz Magdy M , Mathieu Olivier , Ariel Federico , Gutierrez-Marcos Jose , Li Xingwang , Bouché Nicolas , Raynaud Cécile , Latrasse David , Benhamed Moussa 
Published: August 2024

Abstract
The 3D chromatin organization plays a major role in the control of gene expression. However, our comprehension of the governing principles behind nuclear organization remains incomplete. Particularly, the spatial segregation of loci with similar repressive transcriptional states in plants poses a significant yet poorly understood puzzle. In this study, employing a combination of genetics and advanced 3D genomics approaches, we demonstrated that a redistribution of facultative heterochromatin marks in regions usually occupied by constitutive heterochromatin marks disrupts the 3D genome compartmentalisation. This disturbance, in turn, triggers novel chromatin interactions between genic and transposable element (TE) regions. Interestingly, our results imply that epigenetic features, constrained by genetic factors, intricately mold the landscape of 3D genome organisation. This study sheds light on the profound genetic-epigenetic interplay that underlies the regulation of gene expression within the intricate framework of the 3D genome. Our findings highlight the complexity of the relationships between genetic determinants and epigenetic features in shaping the dynamic configuration of the 3D genome.
KREH2 helicase represses ND7 mRNA editing in procyclic-stage Trypanosoma brucei by opposite modulation of canonical and ‘moonlighting’ gRNA utilization creating a proposed mRNA structure
Authors: Meehan Joshua , Ivens Alasdair , Grote Scott , Rodshagen Tyler , Chen Zihao , Goode Cody , Sharma Sunil K , Kumar Vikas , Frese Addison , Goodall Zachary , McCleskey Laura , Sechrist Rebecca , Zeng Lanying , Savill Nicholas J , Rouskin Silvi , Schnaufer Achim , McDermott Suzanne M , Cruz-Reyes Jorge 
Published: August 2024

Abstract
Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical ‘terminator’ gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a ‘moonlighting’ gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2’s novel dual role tunes mitochondrial gene expression in either direction during development.
Loss of DNA glycosylases improves health and cognitive function in a C. elegans model of human tauopathy
Authors: Tiwari Vinod , Buvarp Elisabeth , Borbolis Fivos , Puligilla Chandrakala , Croteau Deborah L , Palikaras Konstantinos , Bohr Vilhelm A 
Published: August 2024

Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder representing a major burden on families and society. Some of the main pathological hallmarks of AD are the accumulation of amyloid plaques (Aβ) and tau neurofibrillary tangles. However, it is still unclear how Aβ and tau aggregates promote specific phenotypic outcomes and lead to excessive oxidative DNA damage, neuronal cell death and eventually to loss of memory. Here we utilized a Caenorhabditis elegans (C. elegans) model of human tauopathy to investigate the role of DNA glycosylases in disease development and progression. Transgenic nematodes expressing a pro-aggregate form of tau displayed altered mitochondrial content, decreased lifespan, and cognitive dysfunction. Genetic ablation of either of the two DNA glycosylases found in C. elegans, NTH-1 and UNG-1, improved mitochondrial function, lifespan, and memory impairment. NTH-1 depletion resulted in a dramatic increase of differentially expressed genes, which was not apparent in UNG-1 deficient nematodes. Our findings clearly show that in addition to its enzymatic activity, NTH-1 has non-canonical functions highlighting its modulation as a potential therapeutic intervention to tackle tau-mediated pathology.
Relative Effectiveness of the MF59-Adjuvanted Influenza Vaccine Versus High-Dose Influenza Vaccine in Older Adults With Influenza Risk Factors During the 2019–2020 US Influenza Season
Authors: Imran Mahrukh , Mills Carrie W , McDermott Kimberly W , Dean Alex , Bogdanov Alina , McGovern Ian , Haag Mendel D M 
Published: August 2024

Abstract

Background
This study estimated the relative vaccine effectiveness (rVE) of the MF59-adjuvanted trivalent influenza vaccine (aTIV) versus high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of influenza-related medical encounters (IRMEs) during the 2019–2020 United States (US) influenza season stratified by the cumulative number of influenza risk factors. A secondary objective evaluated outpatient IRMEs and influenza- and pneumonia-related hospitalizations.

Methods
This retrospective cohort study included US adults ≥65 years old vaccinated with aTIV or HD-TIV between 1 August 2019 and 31 January 2020. Electronic health records linked to claims were used to ascertain exposure, covariates, risk factors, and outcomes. Multivariable adjusted odds ratios (ORs) were derived using inverse probability of treatment–weighted samples to calculate rVEs independently for individuals with 0, ≥1, 1–2, or ≥3 risk factors.

Results
The study included 1 115 725 aTIV and 2 561 718 HD-TIV recipients. For the primary outcome of any IRME, the analysis found comparable effectiveness between aTIV and HD-TIV (rVE, 5.2% [95% confidence interval {CI}, −5.9% to 15.1%]) among those with 0 risk factors, whereas aTIV was more effective than HD-TIV among patients with ≥1, 1–2, or ≥3 risk factors (12.5% [95% CI, 10.0%–15.0%], 18.4% [95% CI, 13.7%–22.9%], and 10.4% [7.4%–13.3%], respectively). The same trends were observed for the secondary outcomes.

Conclusions
This study demonstrated comparable effectiveness of aTIV and HD-TIV among individuals with no identified risk factors and higher effectiveness of aTIV compared with HD-TIV in preventing any IRMEs, outpatient IRMEs, and influenza- or pneumonia-related hospitalizations among those with at least 1 or multiple high-risk factors in adults ≥65 years old.
Radiation and outflow properties of super-Eddington accretion flows around various mass classes of black holes: Dependence on the accretion rates
Authors: Yoshioka Shogo , Mineshige Shin , Ohsuga Ken , Kawashima Tomohisa , Kitaki Takaaki 
Published: August 2024

Abstract
We perform axisymmetric two-dimensional radiation-hydrodynamic simulations of super-Eddington accretion flow and outflow around black holes to examine the properties of radiation and outflow as functions of the black hole mass and the accretion rate on to the black hole ($\dot{M}_{\rm BH}$). We find that the $\dot{m}_{\rm BH} ({\equiv} \dot{M}_{\rm BH}c^2 /L_{\rm Edd})$ dependence of $L_{\rm rad}/L_{\rm Edd}$ and $L_{\rm mech}/L_{\rm Edd}$ found for a stellar-mass black hole can apply to the high-mass cases, where $L_{\rm rad}$ is the radiation luminosity, $L_{\rm mech}$ is the mechanical luminosity, c is the speed of light, and $L_{\rm Edd}$ is the Eddington luminosity. Such universalities can appear in the regime in which electron scattering opacity dominates over absorption opacity. Further, the normalized isotropic mechanical luminosity $L_{\rm mech}^{\rm ISO}/L_{\rm Edd}$ (evaluated by normalized density and velocity at $\theta =10^\circ$) exhibits a broken power-law relationship with ${\dot{m}}_{\rm BH}$; $L_{\rm mech}^{\rm ISO}/ L_{\rm Edd} \propto {\dot{m}}_{\rm BH}^{2.7}$ (or $\propto {\dot{m}}_{\rm BH}^{0.7}$) below (above) ${\dot{m}}_{\rm BH}\sim 400$. This is because the radial velocity stays nearly constant (or even decreases) below (above) the break with increase of $\dot{m}_{\rm BH}$. We also find that the luminosity ratio is $L_{\rm mech}/L_{\rm rad}^{\rm ISO} \sim 0.05$ at ${\dot{m}}_{\rm BH} \sim 100$, which is roughly consistent with the observations of NLS1, 1H 0323+103.
Leaf transcriptomes from C3, C3-C4 intermediate, and C4Neurachne species give insights into C4 photosynthesis evolution
Authors: Lauterbach Maximilian , Bräutigam Andrea , Clayton Harmony , Saladié Montserrat , Rolland Vivien , Macfarlane Terry D , Weber Andreas P M , Ludwig Martha 
Published: August 2024

Abstract
The C4 photosynthetic pathway is hypothesized to have evolved from the ancestral C3 pathway through progressive changes in leaf anatomy and biochemistry with extant C3-C4 photosynthetic intermediate species representing phenotypes between species demonstrating full C3 and full C4 states. The Australian endemic genus Neurachne is the only known grass group that contains distinct, closely related species that carry out C3, C3-C4 intermediate, or C4 photosynthesis. To explore and understand the molecular mechanisms underlying C4 photosynthesis evolution in this genus, leaf transcriptomes were generated from two C3, three photosynthetic intermediate (proto-Kranz, C2-like, and C2), and two C4Neurachne species. The data were used to reconstruct phylogenetic relationships in Neurachne, which confirmed two independent C4 origins in the genus. Relative transcript abundances substantiated the photosynthetic phenotypes of individual species and highlighted transcriptional investment differences between species, including between the two C4 species. The data also revealed proteins potentially involved in C4 cycle intermediate transport and identified molecular mechanisms responsible for the evolution of C4-associated proteins in the genus.
Evaluation of changes in cardiac longitudinal strain rate in patients with systemic sclerosis undergoing iloprost treatment: an observational study
Authors: Isaia Ivan , Aparo Paola , Castelletti Federica , Regolo Matteo , Aprile Maria Letizia , Fiorenza Paolo , Sambataro Gianluca , Malatino Lorenzo , Colaci Michele 
Published: August 2024

Abstract

Objectives
SSc is characterized by widespread microangiopathy and fibrosis of skin and visceral organs. Left ventricle involvement is usually subclinical, characterized by systolic and/or diastolic dysfunction. The global longitudinal strain (GLS), a validated and reliable technique for the measurement of ventricular longitudinal deformation by means of echocardiography, may detect subclinical systolic dysfunction of SSc myocardium. The improvement of myocardial perfusion by means of intravenous Iloprost administration could ameliorate the contractility of SSc heart. Therefore, we aimed to evaluate GLS in a series of SSc patients prior and after Iloprost infusion.

Methods
Fifteen consecutive SSc patients (age: 54 ± 11 years; 12 females) treated with Iloprost because of the presence/history of digital ulcers underwent echocardiography, including GLS technique. This evaluation was conducted immediately before Iloprost administration and at the end of the 6-h infusion session.

Results
Significant improvement in the mean GLS was observed after Iloprost administration (from −13.5 ± 2.5 to −15 ± 3.3; P = 0.011). The echocardiographic data obtained from the four-chamber view showed the best quality for GLS analysis and showed a highly significant improvement of the strain after Iloprost administration (from −13.4 ± 2.2 to −15.6 ± 3; P = 0.001). The degree of GLS improvement did not correlate with any SSc parameters.

Conclusion
Iloprost administration improved GLS, suggesting that the increase of myocardial perfusion allowed, at least in part, a correction of left ventricular systolic dysfunction. Further studies are needed to confirm these findings, further exploring the mid/long-term effects of Iloprost on myocardial contraction.
Factors associated with long-term opioid use among patients with axial spondyloarthritis or psoriatic arthritis who initiate opioids
Authors: Huang Yun-Ting , Jenkins David A , Yimer Belay Birlie , Jani Meghna 
Published: August 2024

Abstract

Objective
Up to one in five patients with axial spondyloarthritis (AxSpA) or psoriatic arthritis (PsA) newly initiated on opioids transition to long-term use within the first year. This study aimed to investigate individual factors associated with long-term opioid use among opioid new users with AxSpA/PsA.

Methods
Adult patients with AxSpA/PsA and without prior cancer who initiated opioids between 2006 and 2021 were included from Clinical Practice Research Datalink Gold, a national UK primary care database. Long-term opioid use was defined as having ≥3 opioid prescriptions issued within 90 days, or ≥90 days of opioid supply, in the first year of follow-up. Individual factors assessed included sociodemographic, lifestyle factors, medication use and comorbidities. A mixed-effects logistic regression model with patient-level random intercept was used to examine the association of individual characteristics with the odds of long-term opioid use.

Results
In total, 10 300 opioid initiations were identified from 8212 patients (3037 AxSpA; 5175 PsA). The following factors were associated with long-term opioid use: being a current smoker (OR: 1.62; 95%CI: 1.38,1.90), substance use disorder (OR: 2.34, 95%CI: 1.05,5.21), history of suicide/self-harm (OR: 1.84; 95%CI: 1.13,2.99), co-existing fibromyalgia (OR: 1.62; 95%CI: 1.11,2.37), higher Charlson Comorbidity Index (OR: 3.61; 95%CI: 1.69,7.71 for high scores), high MME/day at initiation (OR: 1.03; 95%CI: 1.02,1.03) and gabapentinoid (OR: 2.35; 95%CI: 1.75,3.16) and antidepressant use (OR: 1.69; 95%CI: 1.45,1.98).

Conclusions
In AxSpA/PsA patients requiring pain relief, awareness of lifestyle, sociodemographic and prescribing characteristics associated with higher risk of long-term opioid use can prompt timely interventions such as structured medication reviews and smoking cessation to promote safer prescribing and better patient outcomes.
Demyelination and impaired oligodendrogenesis in the corpus callosum following lead exposure
Authors: Liu Luke L , Emir Uzay , Gu Huiying , Sang Lara T , Sawiak Stephen J , Cannon Jason R , Du Yansheng , Zheng Wei 
Published: August 2024

Abstract
The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate the effects of Pb exposure on oligodendrogenesis in SVZ and myelination in the corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hr before sampling) caused mild Pb accumulation in the corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared with controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wk) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in the corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in the corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimer’s disease, the effect of Pb on myelination was evaluated in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1,000 ppm Pb in drinking water as PbAc2 for 20 wk) revealed a profound demyelination in the corpus callosum compared with controls. Immunostaining of the choroid plexus showed diminished signaling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in the corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis.
Mixtures of phthalates disrupt expression of genes related to lipid metabolism and peroxisome proliferator-activated receptor signaling in mouse granulosa cells
Authors: Alahmadi Hanin , Martinez Stephanie , Farrell Rivka , Bikienga Rafiatou , Arinzeh Nneka , Potts Courtney , Li Zhong , Warner Genoa R 
Published: August 2024

Abstract
Phthalates are a class of known endocrine-disrupting chemicals that are found in common everyday products. Several studies associate phthalate exposure with detrimental effects on ovarian function, including growth and development of the follicle and production of steroid hormones. We hypothesized that dysregulation of the ovary by phthalates may be mediated by phthalate toxicity towards granulosa cells, a major cell type in ovarian follicles responsible for key steps of hormone production and nourishing the developing oocyte. To test the hypothesis that phthalates target granulosa cells, we harvested granulosa cells from adult CD-1 mouse ovaries and cultured them for 96 h in vehicle control, a phthalate mixture, or a phthalate metabolite mixture (0.1 to 100 μg/ml). After culture, we measured metabolism of the phthalate mixture into monoester metabolites by the granulosa cells, finding that granulosa cells do not significantly contribute to ovarian metabolism of phthalates. Immunohistochemistry of phthalate metabolizing enzymes in whole ovaries confirmed that these enzymes are not strongly expressed in granulosa cells of antral follicles and that ovarian metabolism of phthalates likely occurs primarily in the stroma. RNA sequencing of treated granulosa cells identified 407 differentially expressed genes, with overrepresentation of genes from lipid metabolic processes, cholesterol metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Expression of significantly differentially expressed genes related to these pathways was confirmed using qPCR. Our results agree with previous findings that phthalates and phthalate metabolites have different effects on the ovary, but both interfere with PPAR signaling in granulosa cells.
Recent warming and increasing CO2 stimulate growth of dominant trees under no water limitation in South Korea
Authors: Arco Molina Julieta Gabriela , Saurer Matthias , Altmanova Nela , Treydte Kerstin , Dolezal Jiri , Song Jong-Suk , Altman Jan 
Published: August 2024

Abstract
Increases in temperatures and atmospheric CO2 concentration influence the growth performance of trees worldwide. The direction and intensity of tree growth and physiological responses to changing climate do, however, vary according to environmental conditions. Here we present complex, long-term, tree-physiological responses to unprecedented temperature increase in East Asia. For this purpose, we studied radial growth and isotopic (δ13C and δ18O) variations using tree-ring data for the past 100 yr of dominant Quercus mongolica trees from the cool-temperate forests from Hallasan, South Korea. Overall, we found that tree stem basal area increment, intercellular CO2 concentration and intrinsic water-use efficiency significantly increased over the last century. We observed, however, short-term variability in the trends of these variables among four periods identified by change point analysis. In comparison, δ18O did not show significant changes over time, suggesting no major hydrological changes in this precipitation-rich area. The strength and direction of growth–climate relationships also varied during the past 100 yr. Basal area increment (BAI) did not show significant relationships with the climate over the 1924–1949 and 1975–1999 periods. However, over 1950–1974, BAI was negatively affected by both temperature and precipitation, while after 2000, a temperature stimulus was observed. Finally, over the past two decades, the increase in Q. mongolica tree growth accelerated and was associated with high spring–summer temperatures and atmospheric CO2 concentrations and decreasing intrinsic water-use efficiency, δ18O and vapour pressure deficit, suggesting that the photosynthetic rate continued increasing under no water limitations. Our results indicate that the performance of dominant trees of one of the most widely distributed species in East Asia has benefited from recent global changes, mainly over the past two decades. Such findings are essential for projections of forest dynamics and carbon sequestration under climate change.
Enhancing sleep quality for adult patients
Authors: Winegar Rhonda 
Published: August 2024

ABSTRACT
Sleep is critical to a person's physiological and psychological functioning. Approximately 30% to 40% of the general population experiences insomnia, and among patients with mental health conditions, the prevalence of insomnia and other sleep disturbances rises to about 70%. Insomnia is associated with many adverse health issues, including lower immunity, weight gain, elevated BP, and increased mortality, and it is often undiagnosed and either untreated or self-treated. Providers can work together with patients to enact measures—such as implementation of enhanced sleep hygiene, engagement in cognitive behavioral therapy, and treatment of any underlying causes—that can markedly improve patient sleep quality. This article provides an overview of evidence-based best practices and whole-person strategies that NPs can adopt to address poor sleep quality in adult patients, and it serves as a primer for primary care NPs on common presentations of several sleep disorders.
Supervised Disulfiram Should Be Considered First-line Treatment for Alcohol Use Disorder
Authors: Holt Stephen R. 
Published: August 2024

Abstract
Despite the prevalence of alcohol use disorder (AUD) in the United States, the armamentarium of FDA-approved medications available for AUD treatment is remarkably small. Disulfiram, 1 of only 3 approved medications, is consistently designated as a second-line option in national treatment guidelines, citing inconsistent evidence, lack of patient preference, and safety concerns. These concerns, however, stem from a misguided interpretation of the evidence that exclusively relies upon double-blind randomized controlled trials (RCT). When viewed instead as both a medication and a behavioral intervention, open-label RCTs become a more appropriate research method, yielding overwhelmingly favorable efficacy data for disulfiram, and supervised disulfiram, in particular. With these data in mind, supervised disulfiram should be redesignated as a first-line intervention in both treatment guideline creation and clinical pathway tools. The addiction medicine community can no longer afford to neglect this critical therapeutic resource.