bluuebunny/crossref_metadata_2025_split huggingface dataset:
A chart review on surgical myocardial debridging in symptomatic patients: a safe procedure with good long-term clinical outcome and coronary computed tomographic angiography results
Authors: Charaf Zohra , Tanaka Kaoru , Wellens Francis , Nijs Jan , Van Loo Ines , Argacha Jean-Francois , La Meir Mark 
Published: January 2023

AbstractOBJECTIVESMyocardial bridging is mostly diagnosed as an incidental imaging finding but can result in severe vessel compression and significant clinical adverse complications. Since there is still an ongoing debate when to propose surgical unroofing, we studied a group of patients where this was performed as an isolated procedure.METHODSIn 16 patients (38.9 ± 15.7 years, 75% men) who had surgical unroofing for symptomatic isolated myocardial bridges of the left anterior descending artery, we retrospectively analysed symptomatology, medication, imaging modalities used, operative techniques, complications and long-term outcome. Computed tomographic fractional flow reserve was calculated to understand its potential value for decision-making.RESULTSMost procedures were performed on-pump (75%, mean cardiopulmonary bypass 56.5 ± 27.9 min, mean aortic cross-clamping 36.4 ± 19.7 min). Three patients needed a left internal mammary artery bypass since the artery dived inside the ventricle. There were no major complications or deaths. The mean follow-up was 5.5 years. Although there was a dramatic improvement in symptoms, still 31% experienced atypical chest pain at various moments during follow-up. Postoperative radiological control was performed in 88%, showing no residual compression or recurrent myocardial bridge and patent bypass if performed. All postoperative computed tomographic flow calculations (7) showed a normalization of coronary flow.CONCLUSIONSSurgical unroofing for symptomatic isolated myocardial bridging is a safe procedure. Patient selection remains difficult but introducing standard coronary computed tomographic angiography with flow calculations could be helpful in preoperative decision-making and during follow-up.
Climate Change, Energy Transition, and Constitutional Identity
Authors: Maloy J S 
Published: January 2023

AbstractThrough its potential to contribute to mass suffering, economic disruption, and social unrest, climate change poses a security threat to the constitutional identities of states (as democratic, autocratic, or hybrid regimes). This paper proposes a conceptual framework of mediated causality for climatic impacts on constitutional identity and engages in novel theory-building for one mediating vector of change: the post-fossil energy transition. Theories of the “oil curse” and of “carbon democracy” are compared and critiqued for their contributions to understanding the potential impacts of decarbonized energy systems on democracy. Two counterintuitive conclusions emerge. First, transitioning away from petroleum may not result in increased democratization, as the oil curse implies. Second, post-fossil energy systems are unlikely to become structurally decentralized, as advocates of “energy democracy” suppose, and may even need to remain centralized in order for popular mobilization around energy to help maintain or reinvigorate democratic rights.
Not so weak PICO: leveraging weak supervision for participants, interventions, and outcomes recognition for systematic review automation
Authors: Dhrangadhariya Anjani , Müller Henning 
Published: January 2023

Abstract

Objective
The aim of this study was to test the feasibility of PICO (participants, interventions, comparators, outcomes) entity extraction using weak supervision and natural language processing.

Methodology
We re-purpose more than 127 medical and nonmedical ontologies and expert-generated rules to obtain multiple noisy labels for PICO entities in the evidence-based medicine (EBM)-PICO corpus. These noisy labels are aggregated using simple majority voting and generative modeling to get consensus labels. The resulting probabilistic labels are used as weak signals to train a weakly supervised (WS) discriminative model and observe performance changes. We explore mistakes in the EBM-PICO that could have led to inaccurate evaluation of previous automation methods.

Results
In total, 4081 randomized clinical trials were weakly labeled to train the WS models and compared against full supervision. The models were separately trained for PICO entities and evaluated on the EBM-PICO test set. A WS approach combining ontologies and expert-generated rules outperformed full supervision for the participant entity by 1.71% macro-F1. Error analysis on the EBM-PICO subset revealed 18–23% erroneous token classifications.

Discussion
Automatic PICO entity extraction accelerates the writing of clinical systematic reviews that commonly use PICO information to filter health evidence. However, PICO extends to more entities—PICOS (S—study type and design), PICOC (C—context), and PICOT (T—timeframe) for which labelled datasets are unavailable. In such cases, the ability to use weak supervision overcomes the expensive annotation bottleneck.

Conclusions
We show the feasibility of WS PICO entity extraction using freely available ontologies and heuristics without manually annotated data. Weak supervision has encouraging performance compared to full supervision but requires careful design to outperform it.
Forages and Pastures Symposium: revisiting mechanisms, methods, and models for altering forage cell wall utilization for ruminants
Authors: Tedeschi Luis O , Adams Jordan M , Vieira Ricardo A M 
Published: January 2023

AbstractSeveral ruminant animals rely almost exclusively on the complex polysaccharide matrix from the plant cell wall (CW) as their primary energy source via volatile fatty acids produced through ruminal and some hindgut fermentation processes. The CW contains different types and proportions of polysaccharides, proteins, phenolic compounds, and minerals in their macromolecular structure that influence the rate and extent of fiber digestion and selective retention of particulate matter due to its physical characteristics (buoyancy and comminuting) in the reticulorumen. The biosynthetic formation of the CW dictates possible manipulation mechanisms (targeted plant and microbes selection) and processing methods (physical, chemical, microbial, and enzymatic treatments and the use of genetically engineered bacteria) to increase its digestibility, leading to better utilization of the CW by the ruminant animal and hopefully lower the contribution of ruminants’ greenhouse gas emissions. Early studies on lignin biosynthesis have led to more advanced studies focusing on replacing traditional monolignols with homopolymers that are easier to deconstruct or degrade. Concurrently, laboratory methods must be developed, evaluated, and modified to accurately reflect the digestibility and nutritive value of CW brought about by modern manipulation mechanisms or processing methods. However, the laboratory methods must also be reliable, precise, feasible, trivial, easy to implement, and cost-effective, but at the same time environmentally friendly and aware. For instance, although the acid detergent lignin has been demonstrated to behave uniformly as a nutritional entity, its chemical determination and association with carbohydrates still lack consensus. Spectroscopy (near-infrared and Raman) and in vitro gas production techniques have been adopted to assess plant chemical composition and nutritive value, but an incomplete understanding of the impacts caused by disrupting the CW for sample processing still exists. Different variations of multicompartmental and time- and age-dependent mathematical models have been proposed to determine the ruminal rates of degradation and passage of fiber. However, low-quality and incomplete data due to inconsistent marker results used to determine passage rates and transit time of fiber in the gastrointestinal tract have hindered advancements and adoptions of the next generation of computer models to understand ruminal fiber degradation.
Hot white dwarfs and pre-white dwarfs discovered with SALT
Authors: Jeffery C S , Werner K , Kilkenny D , Miszalski B , Monageng I , Snowdon E J 
Published: January 2023

ABSTRACT
The Southern African Large Telescope survey of helium-rich hot subdwarfs aims to explore evolutionary pathways among groups of highly evolved stars. The selection criteria mean that several hot white dwarfs and related objects have also been included. This paper reports the discovery and analysis of eight new very hot white dwarf and pre-white dwarf stars with effective temperatures exceeding 100 000 K. They include two PG1159 stars, one DO white dwarf, three O(He), and two O(H) stars. One of the O(H) stars is the central star of a newly discovered planetary nebula, and the other is the hottest ‘naked’ O(H) star. Both of the PG1159 stars are GW Vir variables, one being the hottest GW Vir star measured and a crucial test for pulsation stability models. The DO white dwarf is also the hottest in its class.
Identification and characterization of RNA binding sites for (p)ppGpp using RNA-DRaCALA
Authors: Jagodnik Jonathan , Tjaden Brian , Ross Wilma , Gourse Richard L 
Published: January 2023

Abstract
Ligand-binding RNAs (RNA aptamers) are widespread in the three domains of life, serving as sensors of metabolites and other small molecules. When aptamers are embedded within RNA transcripts as components of riboswitches, they can regulate gene expression upon binding their ligands. Previous methods for biochemical validation of computationally predicted aptamers are not well-suited for rapid screening of large numbers of RNA aptamers. Therefore, we utilized DRaCALA (Differential Radial Capillary Action of Ligand Assay), a technique designed originally to study protein-ligand interactions, to examine RNA-ligand binding, permitting rapid screening of dozens of RNA aptamer candidates concurrently. Using this method, which we call RNA-DRaCALA, we screened 30 ykkC family subtype 2a RNA aptamers that were computationally predicted to bind (p)ppGpp. Most of the aptamers bound both ppGpp and pppGpp, but some strongly favored only ppGpp or pppGpp, and some bound neither. Expansion of the number of biochemically verified sites allowed construction of more accurate secondary structure models and prediction of key features in the aptamers that distinguish a ppGpp from a pppGpp binding site. To demonstrate that the method works with other ligands, we also used RNA DRaCALA to analyze aptamer binding by thiamine pyrophosphate.
Poison cassette exon splicing ofSRSF6regulates nuclear speckle dispersal and the response to hypoxia
Authors: de Oliveira Freitas Machado Camila , Schafranek Michal , Brüggemann Mirko , Hernández Cañás María Clara , Keller Mario , Di Liddo Antonella , Brezski Andre , Blümel Nicole , Arnold Benjamin , Bremm Anja , Wittig Ilka , Jaé Nicolas , McNicoll François , Dimmeler Stefanie , Zarnack Kathi , Müller-McNicoll Michaela 
Published: January 2023

AbstractHypoxia induces massive changes in alternative splicing (AS) to adapt cells to the lack of oxygen. Here, we identify the splicing factor SRSF6 as a key factor in the AS response to hypoxia. The SRSF6 level is strongly reduced in acute hypoxia, which serves a dual purpose: it allows for exon skipping and triggers the dispersal of nuclear speckles. Our data suggest that cells use dispersal of nuclear speckles to reprogram their gene expression during hypoxic adaptation and that SRSF6 plays an important role in cohesion of nuclear speckles. Down-regulation of SRSF6 is achieved through inclusion of a poison cassette exon (PCE) promoted by SRSF4. Removing the PCE 3′ splice site using CRISPR/Cas9 abolishes SRSF6 reduction in hypoxia. Aberrantly high SRSF6 levels in hypoxia attenuate hypoxia-mediated AS and impair dispersal of nuclear speckles. As a consequence, proliferation and genomic instability are increased, while the stress response is suppressed. The SRSF4–PCE–SRSF6 hypoxia axis is active in different cancer types, and high SRSF6 expression in hypoxic tumors correlates with a poor prognosis. We propose that the ultra-conserved PCE of SRSF6 acts as a tumor suppressor and that its inclusion in hypoxia is crucial to reduce SRSF6 levels. This may prevent tumor cells from entering the metastatic route of hypoxia adaptation.
DPC29promotes post-initiation mitochondrial translation inSaccharomyces cerevisiae
Authors: Hubble Kyle A , Henry Michael F 
Published: January 2023

AbstractMitochondrial ribosomes synthesize essential components of the oxidative phosphorylation (OXPHOS) system in a tightly regulated process. In the yeast Saccharomyces cerevisiae, mitochondrial mRNAs require specific translational activators, which orchestrate protein synthesis by recognition of their target gene's 5'-untranslated region (UTR). Most of these yeast genes lack orthologues in mammals, and only one such gene-specific translational activator has been proposed in humans—TACO1. The mechanism by which TACO1 acts is unclear because mammalian mitochondrial mRNAs do not have significant 5'-UTRs, and therefore must promote translation by alternative mechanisms. In this study, we examined the role of the TACO1 orthologue in yeast. We found this 29 kDa protein to be a general mitochondrial translation factor, Dpc29, rather than a COX1-specific translational activator. Its activity was necessary for the optimal expression of OXPHOS mtDNA reporters, and mutations within the mitoribosomal large subunit protein gene MRP7 produced a global reduction of mitochondrial translation in dpc29Δ cells, indicative of a general mitochondrial translation factor. Northern-based mitoribosome profiling of dpc29Δ cells showed higher footprint frequencies at the 3' ends of mRNAs, suggesting a role in translation post-initiation. Additionally, human TACO1 expressed at native levels rescued defects in dpc29Δ yeast strains, suggesting that the two proteins perform highly conserved functions.
Cryo-EM structure of the fully assembled Elongator complex
Authors: Jaciuk Marcin , Scherf David , Kaszuba Karol , Gaik Monika , Rau Alexander , Kościelniak Anna , Krutyhołowa Rościsław , Rawski Michał , Indyka Paulina , Graziadei Andrea , Chramiec-Głąbik Andrzej , Biela Anna , Dobosz Dominika , Lin Ting-Yu , Abbassi Nour-el-Hana , Hammermeister Alexander , Rappsilber Juri , Kosinski Jan , Schaffrath Raffael , Glatt Sebastian 
Published: January 2023

AbstractTransfer RNA (tRNA) molecules are essential to decode messenger RNA codons during protein synthesis. All known tRNAs are heavily modified at multiple positions through post-transcriptional addition of chemical groups. Modifications in the tRNA anticodons are directly influencing ribosome decoding and dynamics during translation elongation and are crucial for maintaining proteome integrity. In eukaryotes, wobble uridines are modified by Elongator, a large and highly conserved macromolecular complex. Elongator consists of two subcomplexes, namely Elp123 containing the enzymatically active Elp3 subunit and the associated Elp456 hetero-hexamer. The structure of the fully assembled complex and the function of the Elp456 subcomplex have remained elusive. Here, we show the cryo-electron microscopy structure of yeast Elongator at an overall resolution of 4.3 Å. We validate the obtained structure by complementary mutational analyses in vitro and in vivo. In addition, we determined various structures of the murine Elongator complex, including the fully assembled mouse Elongator complex at 5.9 Å resolution. Our results confirm the structural conservation of Elongator and its intermediates among eukaryotes. Furthermore, we complement our analyses with the biochemical characterization of the assembled human Elongator. Our results provide the molecular basis for the assembly of Elongator and its tRNA modification activity in eukaryotes.
Detection of unintended on-target effects in CRISPR genome editing by DNA donors carrying diagnostic substitutions
Authors: Lackner Martin , Helmbrecht Nelly , Pääbo Svante , Riesenberg Stephan 
Published: January 2023

AbstractCRISPR nucleases can introduce double-stranded DNA breaks in genomes at positions specified by guide RNAs. When repaired by the cell, this may result in the introduction of insertions and deletions or nucleotide substitutions provided by exogenous DNA donors. However, cellular repair can also result in unintended on-target effects, primarily larger deletions and loss of heterozygosity due to gene conversion. Here we present a strategy that allows easy and reliable detection of unintended on-target effects as well as the generation of control cells that carry wild-type alleles but have demonstratively undergone genome editing at the target site. Our ‘sequence-ascertained favorable editing’ (SAFE) donor approach relies on the use of DNA donor mixtures containing the desired nucleotide substitutions or the wild-type alleles together with combinations of additional ‘diagnostic’ substitutions unlikely to have any effects. Sequencing of the target sites then results in that two different sequences are seen when both chromosomes are edited with ‘SAFE’ donors containing different sets of substitutions, while a single sequence indicates unintended effects such as deletions or gene conversion. We analyzed more than 850 human embryonic stem cell clones edited with ‘SAFE’ donors and detect all copy number changes and almost all clones with gene conversion.
Structural insights into translation regulation by the THF-II riboswitch
Authors: Xu Lilei , Xiao Yu , Zhang Jie , Fang Xianyang 
Published: January 2023

Abstract
In bacteria, expression of folate-related genes is controlled by the tetrahydrofolate (THF) riboswitch in response to specific binding of THF and its derivatives. Recently, a second class of THF riboswitches, named THF-II, was identified in Gram-negative bacteria, which exhibit distinct architecture from the previously characterized THF-I riboswitches found in Gram-positive bacteria. Here, we present the crystal structures of the ligand-bound THF-II riboswitch from Mesorhizobium loti. These structures exhibit a long rod-like fold stabilized by continuous base pair and base triplet stacking across two helices of P1 and P2 and their interconnecting ligand-bound binding pocket. The pterin moiety of the ligand docks into the binding pocket by forming hydrogen bonds with two highly conserved pyrimidines in J12 and J21, which resembles the hydrogen-bonding pattern at the ligand-binding site FAPK in the THF-I riboswitch. Using small-angle X-ray scattering and isothermal titration calorimetry, we further characterized the riboswitch in solution and reveal that Mg2+ is essential for pre-organization of the binding pocket for efficient ligand binding. RNase H cleavage assay indicates that ligand binding reduces accessibility of the ribosome binding site in the right arm of P1, thus down-regulating the expression of downstream genes. Together, these results provide mechanistic insights into translation regulation by the THF-II riboswitch.
No Sufficient Evidence for an Immediate Hypoalgesic Effect of Spinal Manual Therapy on Pressure Pain Thresholds in Asymptomatic and Chronic Pain Populations: A Systematic Review and Meta-Analysis
Authors: Jung Andres , Adamczyk Waclaw M , Ahmed Abdallah , van der Schalk Lea , Poesl Matthias , Luedtke Kerstin , Szikszay Tibor M 
Published: January 2023

Abstract

Objective
Spinal manual therapy (SMT) is often used to treat patients with spinal disorders; however, the underlying mechanisms of SMT are not fully understood. This systematic review and meta-analysis investigates the effect of SMT compared with sham treatment or no intervention on local or remote (segmental or non-segmental) pressure pain thresholds (PPTs) in patients with chronic musculoskeletal conditions and people who are pain free.

Methods
A systematic search was conducted in the PubMed, Cochrane Library, Web of Science, and CINAHL databases. Randomized controlled trials investigating the effect of SMT on PPTs in patients with chronic musculoskeletal conditions and in people who were pain free were included. Quality assessment and evidence synthesis were performed according to Cochrane Handbook recommendations. A meta-analysis was performed using standardized mean difference and 95% CIs.

Results
Twenty-two reports were included in the present review. There were no significant results for an immediate effect of SMT on local (low certainty of evidence), remote (segmental) (low certainty of evidence), and remote (non-segmental) (low certainty of evidence) PPTs in patients with chronic pain as well as on local (moderate certainty of evidence) and remote (segmental) (low certainty of evidence) PPTs in people who were pain free. A small but significant effect (standardized mean difference = 0.26; 95% CI = 0.01 to 0.51; low certainty of evidence) was observed on remote (non-segmental) PPTs in people who were pain free, which was not considered a meaningful effect size.

Conclusion
No immediate, consistent, or meaningful hypoalgetic effect of SMT was shown on PPTs on various body areas. Involvement of spinal or supraspinal underlying mechanisms were, therefore, not confirmed via PPTs but should still be investigated using methods designed to assess central nervous pain processing.

Impact
No consistent and meaningful hypoalgesic effects of spinal manual therapy were demonstrated on PPTs in participants who were pain free and in patients with chronic musculoskeletal disorders.
The joint effects of nanoplastics and TBBPA on neurodevelopmental toxicity inCaenorhabditis elegans
Authors: Zhao Kunming , Zhang Ying , Liu Mingyuan , Huang Yuecheng , Wang Siyan , An Jing , Wang Yan , Shang Yu 
Published: January 2023

AbstractBoth of nanoplastics (NPs) and Tetrabromobisphenol A (TBBPA) are organic pollutants widely detected in the environment and organisms. The large specific surface area of NPs makes them ideal vectors for carrying various toxicants, such as organic pollutants, metals, or other nanomaterials, posing potential threats to human health. This study used Caenorhabditis elegans (C. elegans) to investigate the neurodevelopmental toxicity induced by combined exposure of TBBPA and polystyrene NPs. Our results showed that combined exposure caused synergistic inhibitory effects on the survival rate, body length/width, and locomotor ability. Furthermore, the overproduction of reactive oxygen species (ROS), lipofuscin accumulation, and dopaminergic neuronal loss suggested that oxidative stress was involved in induction of neurodevelopmental toxicity in C. elegans. The expressions of Parkinson’s disease related gene (pink-1) and Alzheimer’s disease related gene (hop-1) were significantly increased after combined exposure of TBBPA and polystyrene NPs. Knock out of pink-1 and hop-1 genes alleviated the adverse effects such as growth retardation, locomotion deficits, dopaminergic loss, and oxidative stress induction, indicating that pink-1 and hop-1 genes play an important role in neurodevelopmental toxicity induced by TBBPA and polystyrene NPs. In conclusion, TBBPA and polystyrene NPs had synergistic effect on oxidative stress induction and neurodevelopmental toxicity in C. elegans, which was mediated through increased expressions of pink-1 and hop-1.