bluuebunny/crossref_metadata_2025_split huggingface dataset:
The co-occurrence of genetic variants in the TYR and OCA2 genes confers susceptibility to albinism
Authors: Green David J. , Michaud Vincent , Lasseaux Eulalie , Plaisant Claudio ,   UK Biobank Eye and Vision Consortium, Fitzgerald Tomas , Birney Ewan , Black Graeme C. , Arveiler Benoît , Sergouniotis Panagiotis I. 
Published: September 2024

AbstractAlthough rare genetic conditions are mostly caused by DNA sequence alterations that functionally disrupt individual genes, large-scale studies using genome sequencing have started to unmask additional complexity. Understanding how combinations of variants in different genes shape human phenotypes is expected to provide important insights into the clinical and genetic heterogeneity of rare disorders. Here, we use albinism, an archetypal rare condition associated with hypopigmentation, as an exemplar for the study of genetic interactions. We analyse data from the Genomics England 100,000 Genomes Project alongside a cohort of 1120 individuals with albinism, and investigate the effect of dual heterozygosity for the combination of two established albinism-related variants: TYR:c.1205 G > A (p.Arg402Gln) [rs1126809] and OCA2:c.1327 G > A (p.Val443Ile) [rs74653330]. As each of these changes alone is insufficient to cause disease when present in the heterozygous state, we sought evidence of synergistic effects. We show that, when both variants are present, the probability of receiving a diagnosis of albinism is significantly increased (odds ratio 12.8; 95% confidence interval 6.0 – 24.7; p-value 2.1 ×10−8). Further analyses in an independent cohort, the UK Biobank, support this finding and highlight that heterozygosity for the TYR:c.1205 G > A and OCA2:c.1327 G > A variant combination is associated with statistically significant alterations in visual acuity and central retinal thickness (traits that are considered albinism endophenotypes). The approach discussed in this report opens up new avenues for the investigation of oligogenic patterns in apparently Mendelian disorders.
Direct electrosynthesis and separation of ammonia and chlorine from waste streams via a stacked membrane-free electrolyzer
Authors: Gao Jianan , Ma Qingquan , Wang Zhiwei , Rittmann Bruce E. , Zhang Wen 
Published: September 2024

AbstractElectrosynthesis, a viable path to decarbonize the chemical industry, has been harnessed to generate valuable chemicals under ambient conditions. Here, we present a membrane-free flow electrolyzer for paired electrocatalytic upcycling of nitrate (NO3−) and chloride (Cl−) to ammonia (NH3) and chlorine (Cl2) gases by utilizing waste streams as substitutes for traditional electrolytes. The electrolyzer concurrently couples electrosynthesis and gaseous-product separation, which minimizes the undesired redox reaction between NH3 and Cl2 and thus prevents products loss. Using a three-stacked-modules electrolyzer system, we efficiently processed a reverse osmosis retentate waste stream. This yielded high concentrations of (NH4)2SO4 (83.8 mM) and NaClO (243.4 mM) at an electrical cost of 7.1 kWh per kilogram of solid products, while residual NH3/NH4+ (0.3 mM), NO2− (0.2 mM), and Cl2/HClO/ClO− (0.1 mM) pollutants in the waste stream could meet the wastewater discharge regulations for nitrogen- and chlorine-species. This study underscores the value of pairing appropriate half-reactions, utilizing waste streams to replace traditional electrolytes, and merging product synthesis with separation to refine electrosynthesis platforms.
Absolute quantitative and base-resolution sequencing reveals comprehensive landscape of pseudouridine across the human transcriptome
Authors: Xu Haiqi , Kong Linzhen , Cheng Jingfei , Al Moussawi Khatoun , Chen Xiufei , Iqbal Aleema , Wing Peter A. C. , Harris James M. , Tsukuda Senko , Embarc-Buh Azman , Wei Guifeng , Castello Alfredo , Kriaucionis Skirmantas , McKeating Jane A. , Lu Xin , Song Chun-Xiao 
Published: September 2024

AbstractPseudouridine (Ψ) is one of the most abundant modifications in cellular RNA. However, its function remains elusive, mainly due to the lack of highly sensitive and accurate detection methods. Here, we introduced 2-bromoacrylamide-assisted cyclization sequencing (BACS), which enables Ψ-to-C transitions, for quantitative profiling of Ψ at single-base resolution. BACS allowed the precise identification of Ψ positions, especially in densely modified Ψ regions and consecutive uridine sequences. BACS detected all known Ψ sites in human rRNA and spliceosomal small nuclear RNAs and generated the quantitative Ψ map of human small nucleolar RNA and tRNA. Furthermore, BACS simultaneously detected adenosine-to-inosine editing sites and N1-methyladenosine. Depletion of pseudouridine synthases TRUB1, PUS7 and PUS1 elucidated their targets and sequence motifs. We further identified a highly abundant Ψ114 site in Epstein–Barr virus-encoded small RNA EBER2. Surprisingly, applying BACS to a panel of RNA viruses demonstrated the absence of Ψ in their viral transcripts or genomes, shedding light on differences in pseudouridylation across virus families.
Management of adult focal nasolacrimal duct stenosis: long-term outcomes of 3D CT-DCG-assisted and endoscopically guided coronary catheter balloon dacryoplasty
Authors: Nowak-Gospodarowicz Izabela , Nowak Rafał , Kinasz Michal , Kicinska Aleksandra Kinga , Rękas Marek , Ali Mohammad Javed 
Published: September 2024

AbstractThe purpose was to evaluate the use of 3D CT-DCG-assisted and endoscopically guided coronary catheter balloon dacryoplasty (CC-BDCP) in adults with focal stenosis of the nasolacrimal duct (NLD) and report their long-term outcomes. A prospective, non-randomized, single-center clinical study was performed, and the patients underwent endoscopy-guided CC-BDCP using percutaneous transluminal coronary angioplasty (PTCA) balloon catheters. 25 patients were enrolled in the study. The CC-BDCP procedure was performed in 21 of 25 (84%) patients, and the remaining 4 (16%) patients had significant procedural difficulties due to unfavorable anatomical conditions. Of the 21 patients, 10 (47.6%) were procedurally assessed as “easy” (eCC-BDCP) and in 11 (52.4%) as procedurally “difficult” (dCC-BDCP). Values on Munk's epiphora intensity scale changed overall from 4.0 preoperatively to 1.4 ± 1.6 (p = 0.00001) postoperatively overall. FDDT changed overall from 2.9 ± 0.3 to 1.1 ± 1.2 after treatment (p = 0.00008) (from 2.8 ± 0.4 to 0.3 ± 0.6 in the eCC-BDCP group and from 2.9 ± 0.3 to 1.4 ± 1.2 in the dCC-BDCP group (p = 0.01352). The anatomical and functional success rate was 77% overall, 90% in the eCC-BDCP group, and 64% in the dCC-BDCP group. The CC-BDCP led to a statistically significant decrease in epiphora in a particular group of adult patients with demonstrable focal stenosis of the NLD.
Disquisition on convergence, stability, and data dependence for a new fast iterative process
Authors: Murali A. , Muthunagai K. 
Published: September 2024

AbstractThis paper introduces a novel fast iterative process designed for approximating fixed points of contraction and weak contraction mappings. The study presents strong convergence results for this newly proposed iterative process, and proving its efficiency. Analytical and numerical evidences are provided to establish that the proposed iterative method converges more rapidly than several existing processes. Furthermore, stability results and dependence analysis are presented for the newly developed iterative process, enhancing its practical applicability and robustness.
Individual and joint exposure to air pollutants and patterns of multiple chronic conditions
Authors: Dai Weifang , Xu Weina , Zhou Jiayu , Liu Shanna , Zhou Qingli 
Published: September 2024

AbstractExisting research on the detrimental effects of air pollution and its mixture on multiple chronic conditions (MCC) is not yet fully recognized. Our objective was to examine if individual and joint exposure to air pollution is associated with the incidence and patterns of MCC. Totally 10,231 CHARLS 2015 participants aged over 45 years and 1,938 without MCC were followed up in 2018 and 2020. Residential-levelcumulative personal exposure concentrations of PM1, PM10, PM2.5, CO, O3, NO2, SO2, NO3−, Cl−, NH4+, and SO42− at the residential level were determined utilizing a spatio-temporal random forest model with a spatial resolution of 0.1° × 0.1°. In the cross-sectional and longitudinal research, logistic regression, cox regression analysis, and quantile g-computation were utilized to estimate the single and joint effect with MCC and its patterns, respectively. Interaction analyses and stratified analyses were also performed. A correlation was observed between the prevalence of cardiovascular illnesses and the presence of all 11 major air pollutants. PM2.5, PM10, NH4+, NO3−, CO, and SO42− are associated with an increased frequency of respiratory disorders. An increase of PM2.5, PM1, PM10, NO2, and SO2 (a 10 µg/m3 rise), CO (a 0.1 mg/m3 rise), and PMCs (Cl−, NH4+, NO3−, and SO42−) (a 1 µg/m3 rise) corresponded to the HRs (95% CI) for developing MCC of 1.194 (95% CI: 1.043, 1.367), 1.362 (95% CI: 1.073, 1.728), 1.115 (95% CI: 1.026, 1.212), 1.443 (95% CI: 1.151, 1.808), 3.175 (95% CI: 2.291, 4.401), 1.272 (95% CI: 1.149,1.410), 1.382 (95% CI: 1.011, 1.888), 1.107 (95% CI: 1.003, 1.222), 1.035 (95% CI: 0.984, 1.088), and 1.122 (95% CI: 1.086, 1.160), respectively. SO2 was the predominant contributor to the combined effect (HR: 2.083, 95% CI: 1.659–2.508). Gender, age, drinking, and health status could modify the effects of air pollutants on MCC patterns. Long-term exposure to air pollution is correlated to the incidence and patterns of MCC in middle-aged and elderly Chinese individuals. Preventive methods are essential to safeguarding those susceptible to MCC.
Spared ulnar nerve injury results in increased layer III–VI excitability in the pig somatosensory cortex
Authors: Meijs Suzan , Hayward Andrew J. , Gomes Nørgaard Dos Santos Nielsen Thomas , Reidies Bjarkam Carsten , Jensen Winnie 
Published: September 2024

AbstractThis study describes cortical recordings in a large animal nerve injury model. We investigated differences in primary somatosensory cortex (S1) hyperexcitability when stimulating injured and uninjured nerves and how different cortical layers contribute to S1 hyperexcitability after spared ulnar nerve injury. We used a multielectrode array to record single-neuron activity in the S1 of ten female Danish landrace pigs. Electrical stimulation of the injured and uninjured nerve evoked brain activity up to 3 h after injury. The peak amplitude and latency of early and late peristimulus time histogram responses were extracted for statistical analysis. Histological investigations determined the layer of the cortex in which each electrode contact was placed. Nerve injury increased the early peak amplitude compared with that of the control group. This difference was significant immediately after nerve injury when the uninjured nerve was stimulated, while it was delayed for the injured nerve. The amplitude of the early peak was increased in layers III–VI after nerve injury compared with the control. In layer III, S1 excitability was also increased compared with preinjury for the early peak. Furthermore, the late peak was significantly larger in layer III than in the other layers in the intervention and control group before and after injury. Thus, the most prominent increase in excitability occurred in layer III, which is responsible for the gain modulation of cortical output through layer V. Therefore, layer III neurons seem to have an important role in altered brain excitability after nerve injury.
Cancer cell-intrinsic biosynthesis of itaconate promotes tumor immunogenicity
Authors: Wang Zining , Cui Lei , Lin Yanxun , Huo Bitao , Zhang Hongxia , Xie Chunyuan , Zhang Huanling , Liu Yongxiang , Jin Huan , Guo Hui , Li Mengyun , Wang Xiaojuan , Zhou Penghui , Huang Peng , Liu Jinyun , Xia Xiaojun 
Published: September 2024

AbstractThe Krebs cycle byproduct itaconate has recently emerged as an important metabolite regulating macrophage immune functions, but its role in tumor cells remains unknown. Here, we show that increased tumor-intrinsic cis-aconitate decarboxylase (ACOD1 or CAD, encoded by immune-responsive gene 1, Irg1) expression and itaconate production promote tumor immunogenicity and anti-tumor immune responses. Furthermore, we identify thimerosal, a vaccine preservative, as a specific inducer of IRG1 expression in tumor cells but not in macrophages, thereby enhancing tumor immunogenicity. Mechanistically, thimerosal induces itaconate production through a ROS-RIPK3-IRF1 signaling axis in tumor cells. Further, increased IRG1/itaconate upregulates antigen presentation-related gene expression via promoting TFEB nuclear translocation. Intratumoral injection of thimerosal induced itaconate production, activated the tumor immune microenvironment, and inhibited tumor growth in a T cell-dependent manner. Importantly, IRG1 deficiency markedly impaired tumor response to thimerosal treatment. Furthermore, itaconate induction by thimerosal potentiates the anti-tumor efficacy of adoptive T-cell therapy and anti-PD1 therapy in a mouse lymphoma model. Hence, our findings identify a new role for tumor intrinsic IRG1/itaconate in promoting tumor immunogenicity and provide a translational means to increase immunotherapy efficacy.
p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb
Authors: Papismadov Nurit , Levi Naama , Roitman Lior , Agrawal Amit , Ovadya Yossi , Cherqui Ulysse , Yosef Reut , Akiva Hagay , Gal Hilah , Krizhanovsky Valery 
Published: September 2024

AbstractFibrosis and accumulation of senescent cells are common tissue changes associated with aging. Here, we show that the CDK inhibitor p21 (CDKN1A), known to regulate the cell cycle and the viability of senescent cells, also controls the expression of extracellular matrix (ECM) components in senescent and proliferating cells of the fibrotic lung, in a manner dependent on CDK4 and Rb phosphorylation. p21 knockout protects mice from the induction of lung fibrosis. Moreover, inducible p21 silencing during fibrosis development alleviates disease pathology, decreasing the inflammatory response and ECM accumulation in the lung, and reducing the amount of senescent cells. Furthermore, p21 silencing limits fibrosis progression even when introduced during disease development. These findings show that one common mechanism regulates both cell cycle progression and expression of ECM components, and suggest that targeting p21 might be a new approach for treating age-related fibrotic pathologies.
Spatially resolved plasma composition evolution in a solar flare – The effect of reconnection outflow
Authors: To Andy S. H. , Brooks David H. , Imada Shinsuke , French Ryan J. , van Driel-Gesztelyi Lidia , Baker Deborah , Long David M. , Ashfield IV William , Hayes Laura A. 
Published: September 2024

Context. Solar flares exhibit complex variations in elemental abundances compared to photospheric values. These abundance variations, characterized by the first ionization potential (FIP) bias, remain challenging to interpret.
Aims. We aim to (1) examine the spatial and temporal evolution of coronal abundances in the X8.2 flare on 2017 September 10, and (2) provide a new scenario to interpret the often observed high FIP bias loop top, and provide further insight into differences between spatially resolved and Sun-as-a-star flare composition measurements.
Methods. We analyzed 12 Hinode/Extreme-ultraviolet Imaging Spectrometer (EIS) raster scans spanning 3.5 hours, employing both Ca XIV 193.87 Å/Ar XIV 194.40 Å and Fe XVI 262.98 Å/S XIII 256.69 Å composition diagnostics to derive FIP bias values. We used the Markov Chain Monte Carlo (MCMC) differential emission measure (DEM) method to obtain the distribution of plasma temperatures, which forms the basis for the FIP bias calculations.
Results. Both the Ca/Ar and Fe/S composition diagnostics consistently show that flare loop tops maintain high FIP bias values of > 2–6, with peak phase values exceeding 4, over the extended duration, while footpoints exhibit photospheric FIP bias of ∼1. The consistency between these two diagnostics forms the basis for our interpretation of the abundance variations.
Conclusions. We propose that this variation arises from a combination of two distinct processes: high FIP bias plasma downflows from the plasma sheet confined to loop tops, and chromospheric evaporation filling the loop footpoints with low FIP bias plasma. Mixing between these two sources produces the observed gradient. Our observations show that the localized high FIP bias signature at loop tops is likely diluted by the bright footpoint emission in spatially averaged measurements. The spatially resolved spectroscopic observations enabled by EIS prove critical for revealing this complex abundance variation in loops. Furthermore, our observations show clear evidence that the origin of hot flare plasma in flaring loops consists of a combination of both directly heated plasma in the corona and from ablated chromospheric material; and our results provide valuable insights into the formation and composition of loop top brightenings, also known as EUV knots, which are a common feature at the tops of flare loops.
The observational evidence that all microflares that accelerate electrons to high energies are rooted in sunspots
Authors: Battaglia Andrea Francesco , Krucker Säm , Veronig Astrid M. , Stiefel Muriel Zoë , Warmuth Alexander , Benz Arnold O. , Ryan Daniel F. , Collier Hannah , Harra Louise 
Published: September 2024

Context. In general, large solar flares are more efficient at accelerating high-energy electrons than microflares. Nonetheless, sometimes microflares that accelerate electrons to high energies are observed. Their origin is unclear.
Aims. We statistically characterized microflares with strikingly hard spectra in the hard X-ray (HXR) range, which means that they are efficient at accelerating high-energy electrons. We refer to these events as “hard microflares”.
Methods. We selected 39 hard microflares, based on their spectral hardness estimated from the Solar Orbiter/STIX HXR quicklook light curves in two energy bands. The statistical analysis is built on spectral and imaging information from STIX combined with extreme ultraviolet (EUV) and magnetic field maps from SDO/AIA and SDO/HMI.
Results. The key observational result is that all hard microflares in this dataset have one of the footpoint rooted directly within a sunspot (either in the umbra or the penumbra). This clearly indicates that the underlying magnetic flux densities are large. For the events with the classic two-footpoints morphology, the absolute value of the mean line-of-sight magnetic flux density (and vector magnetic field strength) at the footpoint rooted within the sunspot ranges from 600 to 1800 G (1500 to 2500 G), whereas the outer footpoint measures from 10 to 200 G (100 to 400 G), therefore about ten times weaker. In addition, approximately 78% of the hard microflares, which exhibited two HXR footpoints, have similar or even stronger HXR flux from the footpoint rooted within the sunspot. This contradicts the magnetic mirroring scenario. The median footpoint separation, measured through HXR observations, is approximately 24 Mm, which aligns with regular events of similar GOES classes. In addition, about 74% of the events could be approximated by a single-loop geometry, demonstrating that hard microflares typically have a relatively simple morphology. Out of these events, around 54% exhibit a relatively flat flare loop geometry.
Conclusions. We conclude that all hard microflares are rooted in sunspots, which implies that the magnetic field strength plays a key role in efficiently accelerating high-energy electrons, with hard HXR spectra associated with strong fields. This key result will allow us to further constrain our understanding of the electron acceleration mechanisms in flares and space plasmas.
Magnetic dissipation in short gamma-ray-burst jets
Authors: Mattia Giancarlo , Del Zanna Luca , Pavan Andrea , Ciolfi Riccardo 
Published: September 2024

Aims. Short gamma-ray bursts originate when relativistic jets emerge from the remnants of binary neutron star (BNS) mergers, as observed in the first multi-messenger event GW170817–GRB 170817A, which coincided with a gravitational wave signal. Both the jet and the remnant are believed to be magnetized, and the presence of magnetic fields is known to influence the jet propagation across the surrounding post-merger environment. In the magnetic interplay between the jet and the environment itself, effects due to a finite plasma conductivity may be important, especially in the first phases of jet propagation. We aim to investigate these effects, from jet launching to its final breakout from the post-merger environment.
Methods. We used the PLUTO numerical code to perform 2D axisymmetric and full 3D resistive relativistic magnetohydrodynamic (MHD) simulations, employing spherical coordinates with spatial radial stretching. We considered and compared different models for physical resistivity, which must be small but still dominating over the intrinsic numerical dissipation (which yields unwanted smearing of structures in any ideal MHD code). Stiff terms in the current density are treated with IMplicit-EXplicit Runge Kutta algorithms for time-stepping. A Synge-like gas (Taub equation of state) is also considered. All simulations were performed using an axisymmetric analytical model for both the jet propagation environment and the jet injection; we leave the case of jet propagation in a realistic environment (i.e., imported from an actual BNS merger simulation) to a future study.
Results. As expected, no qualitative differences are detected due to the effect of a finite conductivity, but significant quantitative differences in the jet structure and induced turbulence are clearly seen in 2D axisymmetric simulations, and we also compare different resistivity models. We see the formation of regions with a resistive electric field parallel to the magnetic field, and nonthermal particle acceleration may be enhanced there. The level of dissipated Ohmic power is also dependent on the various recipes for resistivity. Most of the differences arise before the breakout from the inner environment, whereas once the jet enters the external weakly magnetized environment region, these differences are preserved during further propagation despite the lower grid refinement. Finally, we show and discuss the 3D evolution of the jet within the same environment in order to highlight the emergence of nonaxisymmetric features.