bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered transcription-associated Cas9 targeting in eukaryotic cells
Authors: Goldberg Gregory W. , Kogenaru Manjunatha , Keegan Sarah , Haase Max A. B. , Kagermazova Larisa , Arias Mauricio A. , Onyebeke Kenenna , Adams Samantha , Beyer Daniel K. , Fenyö David , Noyes Marcus B. , Boeke Jef D. 
Published: November 2024

AbstractDNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they provide intrinsic spatial control over DNA targeting activities but naturally lack temporal control. Here we show that engineered Cas9 fusion proteins which bind to nascent RNAs near a protospacer can facilitate spatiotemporal coupling between transcription and DNA targeting at that protospacer: Transcription-associated Cas9 Targeting (TraCT). Engineered TraCT is enabled in eukaryotic yeast or human cells when suboptimal PAM interactions limit basal activity and when one or more nascent RNA substrates are still tethered to the actively transcribed target DNA in cis. Using yeast, we further show that this phenomenon can be applied for selective editing at one of two identical targets in distinct gene loci, or, in diploid allelic loci that are differentially transcribed. Our work demonstrates that temporal control over Cas9’s targeting activity at specific DNA sites may be engineered without modifying Cas9’s core domains and guide RNA components or their expression levels. More broadly, it establishes co-transcriptional RNA binding as a cis-acting mechanism that can conditionally stimulate CRISPR-Cas DNA targeting in eukaryotic cells.
Carbon footprint distributions of lithium-ion batteries and their materials
Authors: Peiseler Leopold , Schenker Vanessa , Schatzmann Karin , Pfister Stephan , Wood Vanessa , Schmidt Tobias 
Published: November 2024

AbstractLithium-ion batteries are pivotal in climate change mitigation. While their own carbon footprint raises concerns, existing studies are scattered, hard to compare and largely overlook the relevance of battery materials. Here, we go beyond traditional carbon footprint analysis and develop a cost-based approach, estimating emission curves for battery materials lithium, nickel and cobalt, based on mining cost data. Combining the emission curves with regionalised battery production announcements, we present carbon footprint distributions (5th, 50th, and 95th percentiles) for lithium-ion batteries with nickel-manganese-cobalt (NMC811, 8-1-1 ratio; 59, 74 and 115 kgCO2 kWh−1) and lithium-iron-phosphate (LFP; 54, 62, 69 kgCO2 kWh−1) cathodes. Our findings reveal the dominating impact of material sourcing over production location, with nickel and lithium identified as major contributors to the carbon footprint and its variance. This research moves the field forward by offering a nuanced understanding of battery carbon footprints, aiding in the design of decarbonisation policies and strategies.
Inequality in pandemic effects on school track placement and the role of social and academic embeddedness
Authors: van de Werfhorst Herman G. , Zwier Dieuwke , Geven Sara , Bol Thijs , Haelermans Carla 
Published: November 2024

AbstractUsing register data and linked student-level sociometric survey data from the Netherlands, this study examines whether the impact of the COVID-19 pandemic on schooling outcomes (track recommendation and track enrollment in the seventh and ninth grades) is conditional on students’ academic and social embeddedness in the school setting. We estimated the counterfactual outcomes for the cohort that went through the school transition during the pandemic based on the outcomes of the pre-pandemic cohort, with similar earlier achievements, schools, and social backgrounds. Results show that the pandemic’s effect on tracking outcomes is weaker than its effect on student test scores elsewhere reported. Nevertheless, the pandemic has had stronger adverse impact on disadvantaged students. Moreover, student self-efficacy, academic motivation, and parental involvement are related to more negligible negative pandemic effects on schooling outcomes. We find no evidence for an association between student grit or parental network centrality and the magnitude of estimated pandemic effects.
A hybrid modelling approach to compare chemical separation technologies in terms of energy consumption and carbon dioxide emissions
Authors: Ignacz Gergo , Beke Aron K. , Toth Viktor , Szekely Gyorgy 
Published: November 2024

AbstractAccurate energy system modelling of chemical separations is a critical component of technology selection to minimize operating costs, energy consumption and emissions. Here we report a hybrid modelling approach based on data-driven and mechanistic models to holistically compare chemical separation performance. Our model can be used to select the most suitable technology for a given chemical separation, such as membrane separation, evaporation, extraction or hybrid configurations, by training a machine learning model to predict solute rejection using an open-access membrane dataset. We estimated an average 40% reduction in energy consumption and carbon dioxide emissions for industrially relevant separations using our methodology. We predicted and analysed 7.1 million solute rejections across several industrial sectors. Pharmaceutical purification could realize carbon dioxide emissions reductions of up to 90% by selecting the most efficient technology. We mapped the reduction in carbon dioxide emissions and the reduction in operating costs globally, establishing parameter thresholds to facilitate corporate and governmental decision-making.
Interleukin-17A is a potential therapeutic target predicted by proteomics for systemic sclerosis patients at high risk of pulmonary arterial hypertension
Authors: Ono Yuuichi , Mogami Akira , Saito Ryuta , Seki Noriyasu , Ishigaki Sho , Takei Hiroshi , Yoshimoto Keiko , Chiba Kenji , Takeuchi Tsutomu , Kaneko Yuko 
Published: November 2024

AbstractWe explored effective therapeutic targets for systemic sclerosis (SSc) patients with high risk for pulmonary arterial hypertension (PAH) by plasma proteomics analysis. A total of fifty-seven patients with SSc were enrolled in the study and the prevalence of PAH was 19.3%. On the other hand, 75.4% of SSc patients showed the ratio of forced vital capacity percentage/diffusing capacity of the lungs for carbon monoxide percentage> 1.6 and met criteria for high risk of PAH. Identification of elevated plasma proteins in SSc patients with high risk of PAH, followed by upstream regulator analysis, predicted interleukin (IL)-17A as a major upstream molecule. Furthermore, we performed in vitro neutralization study using MT-6194, a bispecific antibody targeting both IL-17A and IL-6 receptor. We found that MT-6194 broadly suppressed the increased expression of downstream molecules of IL-17A including IL-17A-related cytokines/chemokines, IL-17A-driven NF$$\kappa$$B pathway and IL-6-driven JAK/STAT pathway which were shown to be increased in SSc patients with high risk of PAH by the proteomics. Consequently, it is revealed that IL-17A is a promising target for early intervention in SSc patients with high risk for PAH.
Realizing high-performance four active plasmonic filters using a single structure
Authors: Elbialy Samar , El-den B. M. , Ashraf Eman 
Published: November 2024

AbstractThis research aims to contribute significantly to the field of plasmonic filtering technology within modern optical communication systems. By focusing on the development of a high-performance, more compact, and efficient design, this study explores the potential of hybrid plasmonic filters to revolutionize optical filtering applications. The approach leverages an innovative active material with electrically tunable permittivity, allowing for dynamic control over the filter’s optical properties. The research specifically examines four types of filters: low-pass filters (LPF), high-pass filters (HPF), band-pass filters (BPF), and band-reject filters (BRF). These filters are designed to operate effectively across a broad wavelength range of 1200–1800 nm, achieving a transmittance exceeding 98% at the output port, while maintaining isolation with transmittance below 2% at the isolated ports. The structure demonstrates a FWHM of approximately 216 nm for the band-pass filter and approximately 223 nm for the band-reject filter, which are considered moderate values, ensuring the versatility and multifunctionality of the design. The ultra-compact size, with a footprint of just 21 µm2, makes these filters particularly advantageous for integration into space-constrained optical communication systems.
Sand bed river dynamics controlling microplastic flux
Authors: Beaumont Hazel , Ockelford Annie , Morris-Simpson Phill 
Published: November 2024

AbstractMicroplastic contamination of river sediments has been found to be pervasive at the global scale and responsive to plastic and sediment bed properties, the flow regime and the river morphology. The physical controls governing the storage, remobilization and pathways of transfer in sand bed rivers remain unquantified. This means it is not currently possible to determine the risks posed by microplastic contamination within these globally significant river systems. Using controlled flume experiments we show that sand bed rivers can store up to 40% of their microplastic load within the sediment bed indicating that these environments can act as resilient sinks of microplastics. By linking bedform dynamics with microplastic transport characteristics we show that similarities exist between granular transport phenomena and the behavior, and hence predictability, of microplastic flux. Specifically, we demonstrate the inverse relationship between bedform celerity and microplastic retention within the bed can be used to predict microplastic flux. Further, we show that, in these environments, microplastic shape is more important than previously thought in controlling the fate of microplastics. Together, these findings are significant since they have important implications for the prediction and hence management of microplastic contamination in sand bed environments.
Comparative analysis of the efficacy of oblique lateral interbody fusion versus transforaminal lumbar interbody fusion in the treatment of lumbar disc herniation
Authors: Chen Daodong , Liu Tao , Du Kunyang , Zhu Zhenjun 
Published: November 2024

AbstractLumbar disc herniation (LDH) often necessitates surgical intervention when conservative treatments fail. Oblique Lateral Interbody Fusion (OLIF) and Transforaminal Lumbar Interbody Fusion (TLIF) are two commonly used techniques for treating LDH, each offering distinct surgical approaches. This study aimed to compare the efficacy of OLIF versus TLIF in terms of pain relief, functional outcomes, spinal alignment correction, fusion success, and postoperative recovery. A retrospective study was conducted on 133 patients who underwent either OLIF (n = 68) or TLIF (n = 65) between January 2020 and December 2022. Data on patient demographics, pain and functional outcomes (measured by Visual Analogue Scale [VAS] and Oswestry Disability Index [ODI]), radiological outcomes (sagittal and coronal Cobb angles, apical vertebra deviation), fusion and collapse rates, and postoperative recovery (ambulation time and hospitalization duration) were collected. Statistical analysis was performed using t-tests and chi-square tests, with significance set at P < 0.05. Both groups demonstrated significant postoperative improvements in pain and functional outcomes. OLIF resulted in significantly better long-term pain reduction (VAS 1.99 ± 0.67 vs. 2.29 ± 0.92, P = 0.03) and greater spinal alignment correction, particularly in sagittal Cobb angle and apical vertebra deviation (P < 0.001). The fusion rate was similar between OLIF (97.92%) and TLIF (96.61%, P = 0.56), but OLIF had a lower collapse rate (8.33% vs. 18.64%, P < 0.001). OLIF also facilitated faster postoperative recovery, with earlier ambulation and shorter hospitalization time (P < 0.001 for both). While both OLIF and TLIF are effective for treating LDH, OLIF offers superior long-term pain relief, better spinal alignment correction, reduced collapse rates, and faster recovery. These findings suggest that OLIF may be a more advantageous option for patients requiring lumbar interbody fusion.
Applying a transformer architecture to intraoperative temporal dynamics improves the prediction of postoperative delirium
Authors: Giesa Niklas , Sekutowicz Maria , Rubarth Kerstin , Spies Claudia Doris , Balzer Felix , Haufe Stefan , Boie Sebastian Daniel 
Published: November 2024

Abstract
Background
Patients who experienced postoperative delirium (POD) are at higher risk of poor outcomes like dementia or death. Previous machine learning models predicting POD mostly relied on time-aggregated features. We aimed to assess the potential of temporal patterns in clinical parameters during surgeries to predict POD.

Methods
Long short-term memory (LSTM) and transformer models, directly consuming time series, were compared to multi-layer perceptrons (MLPs) trained on time-aggregated features. We also fitted hybrid models, fusing either LSTM or transformer models with MLPs. Univariate Spearman’s rank correlations and linear mixed-effect models establish the importance of individual features that we compared to transformers’ attention weights.

Results
Best performance is achieved by a transformer architecture ingesting 30 min of intraoperative parameter sequences. Systolic invasive blood pressure and given opioids mark the most important input variables, in line with univariate feature importances.

Conclusions
Intraoperative temporal dynamics of clinical parameters, exploited by a transformer architecture named TRAPOD, are critical for the accurate prediction of POD.
A catalyst- and solvent-free visible-light-promoted bromination and chlorination of tertiary C(sp3)–H bonds
Authors: Rong Quanjin , Zhang Zhe , Meng Jingyu , Wang Fan , Liu Zhong-Quan 
Published: November 2024

We report herein a visible-light-driven bromination/chlorination of 3° C(sp3)–H bonds without using any catalyst or solvent. This method features high site selectivity, scalability and excellent functional group tolerance, even in complex molecules.
Influence of the C + H2O → H2CO solid-state reaction on astrochemical networks and the formation of complex organic molecules
Authors: Potapov Alexey , Garrod Robin T. 
Published: November 2024

Context. The solid-state reaction C + H2O → H2CO has recently been studied experimentally and claimed as a new ‘non-energetic’ pathway to complex organic and prebiotic molecules in cold astrophysical environments.
Aims. We compared results of astrochemical network modelling with and without the C + H2O surface reaction.
Methods. A typical, generic collapse model in which a dense core forms from initially diffuse conditions was used along with the astrochemical kinetics model MAGICKAL.
Results. The inclusion of the reaction does not notably enhance the abundance of formaldehyde itself; however, it significantly enhances the abundance of methanol (formed by the hydrogenation of formaldehyde) on the dust grains at early times, when the high gas-phase abundance of atomic C leads to relatively rapid adsorption onto the grain surfaces. As a result, the gas-phase abundance of methanol is also increased due to chemical desorption, quickly reaching abundances close to ∼10−9 nH, which decline strongly under late-time, high-density conditions. The reaction also influences the abundances of simple ice species, with the CO2 abundance increased in the earliest, deepest ice layers, while the water-ice abundance is somewhat depressed. The abundances of various complex organic molecules are also affected, with some species becoming more abundant and others less. When gas-phase atomic carbon becomes depleted, the grain-surface chemistry returns to behaviour that would be expected if there had been no new reaction.
Conclusions. Our results show that fundamental reactions involving the simplest atomic and molecular species can be of great importance for the evolution of astrochemical reaction networks, thus providing motivation for future experimental and theoretical studies.
Temporal evolution of axially standing kink motions in solar coronal slabs: An eigenfunction expansion approach
Authors: Gao Yuhong , Li Bo , Shi Mijie , Chen Shaoxia , Yu Hui 
Published: November 2024

Aims. We aim to provide more insights into the applicability of the much-studied discrete leaky modes (DLMs) in classic analyses to solar coronal seismology.
Methods. Under linear ideal pressureless magnetohydrodynamics (MHD), we examined 2D axial fundamental kink motions that arise when localized velocity exciters impact some symmetric slab equilibria. Continuous structuring is allowed. A 1D initial value problem (IVP) is formulated in conjunction with an eigenvalue problem (EVP) for laterally open systems, with no strict boundary conditions (BCs) at infinity. The IVP is solved by eigenfunction expansion, allowing a clear distinction between the contributions from proper eigenmodes and improper continuum eigenmodes. Example solutions are offered for parameters typical of active region loops.
Results. Our solutions show that the system evolves toward long periodicities due to proper eigenmodes (on the order of the axial Alfvén time), whereas the interference of the improper continuum may lead to short periodicities initially (on the order of the lateral Alfvén time). Specializing to the slab axis, we demonstrate that the proper contribution strengthens with the density contrast, but may occasionally be stronger for less steep density profiles. Short periodicities are not guaranteed in the improper contribution, the details of the initial exciter being key. When identifiable, these periodicities tend to agree with the oscillation frequencies expected for DLMs, despite the differences in the BCs between our EVP and classic analyses. The eigenfunction expansion approach enables all qualitative features to be interpreted as the interplay between the initial exciter and some response function, the latter being determined solely by the equilibria.
Conclusions. Classic theories for DLMs can find seismological applications, with time-dependent studies offering additional ways for constraining initial exciters.
Why Median Severity and Ordinal Scale Severity Values should not be used for Injury Burden Results: A Critical Review
Authors: Fuller Colin W. 
Published: November 2024

AbstractInjury burden is a composite measure of injury incidence and mean severity; this parameter has been reported as an output measure from injury surveillance studies in rugby for over 20 years. The benefits of reporting injury burden results have, more recently, been recognised in other sports. This wider use of injury burden as an output measure from injury surveillance studies has, however, highlighted misunderstandings about how to calculate, present and interpret injury burden data. The aim of this critical review is to explain why median severity and ordinal severity scales should not be used to calculate and report injury burden results in injury surveillance studies. Equations are presented to show how injury burden results should be calculated, and graphs and tables are presented to explain the errors that are introduced when median severity and ordinal scales of severity are used instead of mean severity. This critical review is intended to highlight the correct procedures for calculating, reporting and interpreting injury burden results in order to avoid incorrect results, conclusions and injury prevention recommendations being published.
Das muskelinvasive und metastasierte Urothelkarzinom aus Sicht der Pathologie
Authors: Klümper Niklas , Kalogirou Charis , Eckstein Markus 
Published: November 2024

Zusammenfassung

Das muskelinvasive und metastasierte Urothelkarzinom ist eine heterogene Erkrankung mit breitem morphologischem und molekularem Spektrum. Mit der Novelle der WHO-Klassifikation haben sich einige Veränderungen in der Nomenklatur und Einteilung muskelinvasiver und metastasierter Urothelkarzinome ergeben. Aufgrund zunehmender Individualisierung therapeutischer Optionen gewinnt die korrekte Diagnose morphologischer Varianten des Urothelkarzinoms, die mit spezifischen molekularen Alterationen assoziiert sind, zunehmend an Bedeutung. Die morphologischen Varianten korrelieren zudem mit molekularen Subtypen des Urothelkarzinoms. Darüber hinaus sind sowohl morphologische als auch molekulare Subtypen mit immunologischen und anderen molekularen Eigenschaften assoziiert, die z.B. in Form des PD-L1- und des NECTIN-4-Status relevant für moderne Immuntherapien oder Antikörper-Drugkonjugate sein könnten. Mit der anstehenden Zulassung von Erdafitinib (FGFR3-Inhibitor) werden in Zukunft auch molekulare Tumorboards für Patienten mit metastasiertem Urothelkarzinom an Bedeutung gewinnen.
Daily versus Twice Daily Nifedipine for Blood Pressure Control in Pregnancy and Postpartum
Authors: Peterson Jessica A. , Band Isabelle C. , Wang Kelly , Bianco Angela 
Published: November 2024

Objective The objective of this study was to compare 60 mg daily (QD) extended released (XR) nifedipine to 30 mg twice daily (BID) for blood pressure (BP) control antepartum and postpartum.
Study Design This is a retrospective chart review conducted at the Mount Sinai Health System. Patients admitted from January 1, 2015, to April 30, 2021, diagnosed with a hypertensive disorder of pregnancy, who received nifedipine XR 30 mg BID or 60 mg QD for intrapartum or postpartum BP control were included. The primary outcome was the need for up-titration (i.e., the need for an increase in nifedipine dose or addition of another antihypertensive) after reaching one of the study doses (30 mg BID or 60 mg QD). Patients were excluded if they had preexisting renal disease or were already on oral antihypertensives. In a 1:1 ratio between single- and twice-daily dosing groups, the sample size needed to detect a 20% difference in up-titration rate to achieve 0.80 power is 97 patients per group, for a total of 194 patients. This is based on a Pearson chi-square test with a significance level of 0.05.
Results A total of 237 patients were included, 139 (59%) received 30 mg BID and 98 (41%) 60 mg QD. There was no statistically significant difference in the need for an increase in nifedipine dose or addition of another oral antihypertensive agent between those receiving 30 mg BID versus 60 mg QD (33.8 vs. 35.7%; adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.90 [0.50–1.60]; p = 0.71). There was no difference in the need for emergency hypertensive treatment after reaching the study dose (p = 0.19) or readmission for BP control between groups (p > 0.99).
Conclusion These findings suggest that BID dosing does not confer better BP control in the antepartum or postpartum periods. Thus, daily dosing is reasonable and may be preferable for patient convenience and compliance.
Key Points