bluuebunny/crossref_metadata_2025 huggingface dataset:
Canopy2: Tumor Phylogeny Inference by Bulk DNA and Single-Cell RNA Sequencing
Authors: Weideman Ann Marie K. , Wang Rujin , Ibrahim Joseph G. , Jiang Yuchao
Published: January 2025

Tumors are comprised of a mixture of distinct cell populations that differ in terms of genetic makeup and function. Such heterogeneity plays a role in the development of drug resistance and the ineffectiveness of targeted cancer therapies. Insight into this complexity can be obtained through the construction of a phylogenetic tree, which illustrates the evolutionary lineage of tumor cells as they acquire mutations over time. We propose Canopy2, a Bayesian framework that uses single nucleotide variants derived from bulk DNA and single-cell RNA sequencing to infer tumor phylogeny and conduct mutational profiling of tumor subpopulations. Canopy2 uses Markov chain Monte Carlo methods to sample from a joint probability distribution involving a mixture of binomial and beta-binomial distributions, specifically chosen to account for the sparsity and stochasticity of the single-cell data. Canopy2 demystifies the sources of zeros in the single-cell data and separates zeros categorized as non-cancerous (cells without mutations), stochastic (mutations not expressed due to bursting), and technical (expressed mutations not picked up by sequencing). Simulations demonstrate that Canopy2 consistently outperforms competing methods and reconstructs the clonal tree with high fidelity, even in situations involving low sequencing depth, poor single-cell yield, and highly-advanced and polyclonal tumors. We further assess the performance of Canopy2 through application to breast cancer and glioblastoma data, benchmarking against existing methods. Canopy2 is an open-source package available at https://github.com/annweideman/canopy2.
The Role of Animal-Assisted Intervention in Supporting the Preschool-to-School Transition
Authors: Iváncsik Réka , Podráczky Judit , Molnár Marcell , Stromájer Gábor Pál , Csima Melinda
Published: January 2025

The transition from preschool to school is a significant milestone in a child’s life, and the experiences gained during this period have a long-term impact not only on learning outcomes but also on the relationship with school and teachers. Starting school is exciting and filled with anticipation for young children; at the same time, it is also a source of stress that they may struggle to manage properly without support. Our one-group pretest–posttest study aimed to promote the preschool-to-school transition with animal-assisted intervention to reduce anxiety in children entering school. The intervention, which lasted for 24 weeks, involved using of a specially trained therapy rabbit in a classroom setting with the participation of 16 first-grade children. During the periods supported by animal-assisted intervention, there was a greater decrease in anxiety levels for both state and trait anxiety than in weeks when the therapeutic animal was not present in the classroom (p = 0.006; p = 0.02). The anxiety reduction was more pronounced in children who exhibited higher levels of anxiety in the initial measurements (p = 0.037). The results of our study demonstrate for the first time that animal-assisted intervention (especially animal-assisted pedagogy) can be effectively applied in supporting the preschool-to-school transition, especially for children with higher anxiety levels.
Cholecystostomy Indications and Outcomes: Which Patients Will Benefit?
Authors: Koch Rachel , Colonna Alexander
Published: January 2025

Purpose of Review

Percutaneous cholecystostomy (PCT) is a technique used to treat acute cholecystitis in patients who are not surgical candidates for cholecystectomy at the time of presentation. Usage has increased over time and the procedure is nearly always technically successful. We reviewed recent literature to assess for new developments in outcomes and indications for PCT placement.

Recent Findings

Newer data has questioned whether outcomes for patients who get a PCT are better than those managed medically or with cholecystectomy. Multiple studies have shown no difference in mortality between different treatment strategies, and patients who get PCT placement tend to incur higher healthcare utilization.

While PCT is a safe alternative for source control in critically ill patients with cholecystitis, interval cholecystectomy should be performed when possible. Further prospective data is needed to assess long term outcomes and quality of life for patients with PCT.
Close proximity aerial image for precision viticulture. A review
Authors: Molnár Szilárd , Tamás Levente
Published: January 2025

Accurately detecting and localizing vineyard disease detections are essential to reduce production losses. A great variety of scientific work focuses on remote sensing methods, while with current learning-based techniques, a continuous paradigm shift is happening in this domain. Based on a thorough literature review, the need for a remote assistance survey for the detection of vine disease was motivated by the adoption of recent machine learning algorithms. Thus, in this work, the research outputs from the past few years are summarized in the domain of grapevine disease detection. A remote sensing-based distance taxonomy was introduced for different categories of detection methods. This taxonomy is relevant for differentiating among the existing solutions in this domain, the resulting methods being grouped according to the proposed taxonomy. The articles and public datasets cited are collected on the website of this project (https://molnarszilard.github.io/VinEye/).
Evaluating the two-pool decay model for biochar carbon permanence
Authors: Sanei Hamed , Petersen Henrik Ingermann , Chiaramonti David , Masek Ondrej
Published: January 2025

Accurate estimation of biochar carbon permanence is essential for assessing its effectiveness as a carbon dioxide removal (CDR) strategy. The widely adopted framework, based on the two-pool carbon exponential decay model, forms the basis of policy guidelines and national CDR accounting. However, our re-analysis of the meta-data used in this model reveals significant deficiencies in its parameterization, leading to two critical issues. First, the current parameterization assigns a disproportionally low percentage of the labile carbon fraction (C1) relative to the recalcitrant fraction (C2), effectively reducing the model to a single-pool approach. Due to the limited duration of incubation experiments, the decay constant of the labile fraction is incorrectly applied to the entire biochar mass, resulting in a considerable overestimation of the biochar decay rate. Second, our analysis reveals a lack of causal correlation between the assigned proportions of C1 and C2 and key carbonization parameters such as production temperature and hydrogen-to-carbon (H/C) ratios, suggesting that the model does not accurately represent the underlying chemistry. This misalignment contradicts the established relationship between increased biochar stability and a higher degree of carbonization. Consequently, the the parameterization of current model may not adequately reflect the carbon sequestration potential of biochar. While a multi-pool decay model is suitable for predicting the permanence of biochar, the primary issue with the current model lies in its parameterization rather than its structure. To address these limitations, we recommend that future research prioritize the development of a revised multi-pool decay model with improved parameterization, supported by empirical decomposition data from a variety of experimental methods, including incubation studies, accelerated aging experiments, and comprehensive physicochemical characterization. This refined approach will improve the accuracy of biochar permanence estimations, strengthening its role in global carbon management strategies.
On Approaching Normality Through Rectangular Distribution: Industrial Applications to Monitor Electron Gun and File Server Processes
Authors: Riaz Muhammad , Joarder Anwar H. , Omar M. Hafidz , Mahmood Tahir , Abbas Nasir
Published: January 2025

Normal probability distribution is central to most statistical methods and their applications. In many real scenarios, the normality of the underlying phenomenon is not obvious. However, a deeper investigation can lead to normality through some useful links among various models. The current study aims to present one such approach to the Gaussian model by connecting it with the cumulative distribution function of the rectangular distribution. Some characteristics of the rectangular distribution, such as the quantiles, are used to achieve the said objective. Further, the derived distributional results have been used to design a mechanism to monitor the real-time dependent electron gun and file server processes. The performance of the proposed monitoring methodology is evaluated in terms of probability of signal, average run length, extra quadratic loss and cumulative extra quadratic loss. The expressions for probability to signal are derived mathematically and are supported by some tabular results. The results advocate the usefulness of the proposed methodology for effectively monitoring real-life processes.
Effects and mechanisms of digital economy development on corporate carbon emission intensity: empirical evidence from cross-country data
Authors: Yang Da , Yang Zhao , Wu Haoze
Published: January 2025

This study analyzes the effects and mechanisms of the digital economy on corporate carbon emission intensity through theoretical and empirical analysis. It explores the potential of the digital economy as a driving force for reducing corporate carbon emission intensity. It has been found that a country's digital economic development can reduce corporate carbon emission intensity by influencing the country's innovation level, energy structure, and total corporate factor productivity. Further analysis reveals that increased participation in global value chains and rising status will strengthen the carbon emission reduction effect of the digital economy; the carbon emission reduction effect of the digital economy is more evident in countries with weaker environmental regulation intensity.
Mobile phone data for anticipating displacements: practices, opportunities, and challenges
Authors: Aydoğdu Bilgeçağ , Bilgili Özge , Güneş Subhi , Salah Albert Ali
Published: January 2025

The global number of individuals experiencing forced displacement has reached its highest level in the past decade. In this context, the provision of services for those in need requires timely and evidence-based approaches. How can mobile phone data (MPD) based analyses address the knowledge gap on mobility patterns and needs assessments in forced displacement settings? To answer this question, in this paper, we examine the capacity of MPD to function as a tool for anticipatory analysis, particularly in response to natural disasters and conflicts that lead to internal or cross-border displacement. The paper begins with a detailed review of the processes involved in acquiring, processing, and analyzing MPD in forced displacement settings. Following this, we critically assess the challenges associated with employing MPD in policy-making, with a specific focus on issues of user privacy and data ethics. The paper concludes by evaluating the potential benefits of MPD analysis for targeted and effective policy interventions and discusses future research avenues, drawing on recent studies and ongoing collaborations with mobile network operators.
Scalable data assimilation with message passing
Authors: Key Oscar , Takao So , Giles Daniel , Deisenroth Marc Peter
Published: January 2025

Data assimilation is a core component of numerical weather prediction systems. The large quantity of data processed during assimilation requires the computation to be distributed across increasingly many compute nodes; yet, existing approaches suffer from synchronization overhead in this setting. In this article, we exploit the formulation of data assimilation as a Bayesian inference problem and apply a message-passing algorithm to solve the spatial inference problem. Since message passing is inherently based on local computations, this approach lends itself to parallel and distributed computation. In combination with a GPU-accelerated implementation, we can scale the algorithm to very large grid sizes while retaining good accuracy and compute and memory requirements.
Laser interactions with gas jets: electromagnetic pulse emission and nozzle damage
Authors: Bradford P. W. , Ospina-Bohórquez V. , Ehret M. , Henares J.-L. , Puyuelo-Valdes P. , Chodukowski T. , Pisarczyk T. , Rusiniak Z. , Salgado-López C. , Vlachos C. , Scisciò M. , Salvadori M. , Verona C. , Hicks G. S. , Ettlinger O. C. , Najmudin Z. , Marquès J.-R. , Gremillet L. , Santos J. J. , Consoli F. , Tikhonchuk V. T.
Published: January 2025

Understanding the physics of electromagnetic pulse (EMP) emission and nozzle damage is critical for the long-term operation of laser experiments with gas targets, particularly at facilities looking to produce stable sources of radiation at high repetition rates. We present a theoretical model of plasma formation and electrostatic charging when high-power lasers are focused inside gases. The model can be used to estimate the amplitude of gigahertz EMPs produced by the laser and the extent of damage to the gas jet nozzle. Looking at a range of laser and target properties relevant to existing high-power laser systems, we find that EMP fields of tens to hundreds of kV/m can be generated several metres from the gas jet. Model predictions are compared with measurements of EMPs, plasma formation and nozzle damage from two experiments on the VEGA-3 laser and one experiment on the Vulcan Petawatt laser.
All-fiber delivery of 100 W single-frequency laser through 100 m anti-resonant hollow-core fiber without stimulated Brillouin scattering
Authors: Gao Shoufei , Zha Wenxiang , Feng Yujun , Liang Zhixi , Sun Yizhi , Yang Xiaobo , Wang Yingying
Published: January 2025

The flexible delivery of single-frequency lasers is far more challenging than that of conventional lasers due to the onset of stimulated Brillouin scattering (SBS). Here we present the successful delivery of 100 W single-frequency laser power through 100 m of anti-resonant hollow-core fiber (AR-HCF) in an all-fiber configuration, with the absence of SBS. By employing a custom-designed AR-HCF with a mode-field diameter matching that of a large-mode-area panda fiber, the system achieves high coupling efficiency without the need for free-space components or fiber post-processing. The AR-HCF attains a transmission efficiency of 92%, delivering an output power of 100.3 W with a beam quality factor (M2) of 1.22. The absence of SBS is confirmed through monitoring backward light, which shows no increase in intensity. This all-fiber architecture ensures high stability, compactness and efficiency, potentially expanding the application scope of single-frequency lasers in high-precision metrology, optical communication, light detection and ranging systems, gravitational wave detection and other advanced applications.
Evaluating an urgent care antibiotic stewardship intervention: a multi-network collaborative effort
Authors: Park Daniel E. , Roberts Annie L.S. , Hamdy Rana F. , Balthrop Sabrina , Dolan Patrick , Liu Cindy M.
Published: January 2025

Objective:

Urgent care centers (UCCs) have reported high rates of antibiotic prescribing for acute respiratory tract infections. Prior UCC studies have generally been limited to single networks. Broadly generalizable stewardship efforts targeting common diagnoses are needed. This study examines the effectiveness of an antibiotic stewardship intervention in reducing inappropriate prescribing for bronchitis and viral upper respiratory tract infections (URTIs) in UCCs.

Design:

A quality improvement study comparing inappropriate antibiotic prescribing rates in UCCs after the introduction of an antibiotic stewardship intervention.

Setting:

Forty-nine UCCs in 27 different networks from 18 states, including 1 telemedicine site.

Participants:

Urgent care clinicians from a national collaborative of UCCs, all members of the Urgent Care Association.

Methods:

The intervention included signing a commitment statement and selecting from 5 different intervention options during 3 plan-do-study-act cycles. The primary outcome was the percentage of urgent care encounters for viral URTIs or bronchitis with inappropriate prescribing, stratified by clinician engagement and diagnosis. A 3-month baseline and 9-month intervention period were compared using a regression model using a generalized estimating equation.

Results:

Among 15,385 encounters, the intervention was associated with decreases in inappropriate antibiotic prescribing for bronchitis (48% relative decrease, aOR = 0.52; 95% CI, 0.33–0.83) and viral URTIs (33%, aOR = 0.67; 95% CI, 0.55–0.82) among actively engaged clinicians compared to baseline. The intervention did not result in significant changes for clinicians not actively engaged.

Conclusions:

This intervention was associated with reductions in inappropriate prescribing among actively engaged clinicians. Implementing stewardship interventions in UCCs may reduce inappropriate antibiotic prescriptions for common diagnoses; however, active clinician engagement may be necessary.
Controlled Haines jumps in a dual-channel multiphase system: inferring fluid properties from the dynamics of interface motion
Authors: Wang Zhongzheng , Sun Runze , Gan Yixiang , Pereira Jean-Michel , McCue Scott W. , Sauret Emilie
Published: January 2025

When one fluid is injected into a confined geometry such as a porous medium filled with another immiscible fluid, even at an extremely low injection speed, rapid filling of several pore spaces accompanied by retraction of multiple fluid–fluid interfaces can be observed. Such processes with fast liquid redistribution within the solid structure, called Haines jumps, are ubiquitous in many multiphase flow systems, which can impact fluid trapping, energy dissipation and hysteretic saturation in various engineering applications. Inspired by this mechanism, here, we propose a dual-channel structure to realise controlled Haines jumps during fluid displacement processes. Via theoretical analysis and numerical simulations, we show that the dynamics of fluid interfaces during Haines jumps can be quantitatively correlated with the driving capillary pressure and dissipating viscous stress, which enables simultaneous determination of the fluid viscosity and interfacial tension in the dual-channel multiphase system.
Comparison of fast, hybrid imaging architectures for multi-scale, hierarchical aperture arrays
Authors: Thyagarajan Nithyanandan
Published: January 2025

Two major areas of modern radio astronomy, namely, explosive astrophysical transient phenomena and observations of cosmological structures, are driving the design of aperture arrays towards large numbers of low-cost elements consisting of multiple spatial scales spanning the dimensions of individual elements, the size of stations (groupings of individual elements), and the spacing between stations. Such multi-scale, hierarchical aperture arrays require a combination of data processing architectures – pre-correlation beamformer, generic version of fast Fourier transform (FFT)-based direct imager, post-correlation beamformer, and post-correlation FFT imager – operating on different ranges of spatial scales to obtain optimal performance in imaging the entire field of view. Adopting a computational cost metric based on the number of floating point operations, its distribution over the dimensions of discovery space, namely, field of view, angular resolution, polarisation, frequency, and time is examined to determine the most efficient hybrid architectures over the parameter space of hierarchical aperture array layouts. Nominal parameters of specific upcoming and planned arrays – the SKA at low frequencies (SKA-low), SKA-low-core, a proposed long baseline extension to SKA-low (LAMBDA-I), Compact All-Sky Phased Array (CASPA), and a lunar array (FarView-core) – are used to determine the most optimal architecture hierarchy for each from a computational standpoint and provide a guide for designing hybrid architectures for multi-scale aperture arrays. For large, dense-packed layouts, a FFT-based direct imager is most efficient for most cadence intervals, and for other layouts that have relatively lesser number of elements or greater sparsity in distribution, the best architecture is more sensitive to the cadence interval, which in turn is determined by the science goals.
Dichotomy spectrum and reducibility for mean hyperbolic systems
Authors: Feng Jiahui
Published: January 2025

The topological structure of ‘mean dichotomy spectrum’ is shown in this article, as an extension of Sacker–Sell spectrum and non-uniform dichotomy spectrum. With regard to mean hyperbolic systems, the coexistence of expansion and contraction behaviours can lead to non-hyperbolic phenomena during evolution process. To be precise, distinct from uniform and non-uniform hyperbolic cases, error hyperbolic degree

$\varepsilon(t,\tau)$

is vital to depict the spectral manifolds. As application, the reducibility theorem for mean hyperbolic systems is provided to deduce block diagonalization.
Functions with small BMO norm
Authors: Popoli Arturo
Published: January 2025

We characterize the functions with ‘small’ bounded mean oscillation (BMO) norm by establishing the precise connection between the space BMO and class

$A_\infty$

of Muckenhoupt weights. We prove that there exists a universal constant

$c^*_2$

such that

$\Vert f \Vert_{BMO} \lt c^*_2$

if and only if

$\exp f \in A_2$

, where

$c^*_2$

is the sharp constant in the John and Nirenberg inequality. Similarly, in dimension one, we prove that

$\Vert f \Vert_{BLO} \lt 1$

if and only if

$\exp f \in A_1$

. As application we introduce a structure of metric space in

$A_\infty$

and prove that the closed unit ball of

$A_\infty$

is a Banach space.
Observer-rated environmental sensitivity and its characterization at behavioral, genetic, and physiological levels
Authors: Weyn Sofie , Lionetti Francesca , Klein Daniel N. , Aron Elaine , Aron Arthur , Hayden Elizabeth P. , Dougherty Lea R. , Singh Shiva , Waszczuk Monika , Kotov Roman , Docherty Anna , Shabalin Andrey , Pluess Michael
Published: January 2025

This study investigated the psychometric properties of the Highly Sensitive Child-Rating System (HSC-RS), the existence of sensitivity groups, and the characterization of sensitivity at behavioral, genetic, and physiological levels in 541 preschoolers (M(SD)age = 3.56(0.27); 45%male; 87%Caucasian). Temperament, genetic, cortisol, and electroencephalography asymmetry data were collected in subsamples (n = 94-476). Results showed a reliable observational measure of sensitivity. Confirmatory factor and latent class analysis supported a one-factor solution and three sensitivity groups, that are a low (23.3%), medium (54.2%), and a high (22.5%) sensitivity group. Hierarchical regression analyses showed moderate associations between HSC-RS and observed temperament traits (i.e., behavioral level). In addition, a small negative association between HSC-RS and a genome-wide association study polygenic risk score (GWAS PGS) for Attention Deficit Hyperactivity Disorder was found. No relations with candidate genes, other GWAS PGS phenotypes, and physiological measures were found. Implications of our findings and possible explanations for a lack of these associations are discussed.
Measuring child food poverty: understanding the gap to achieving minimum dietary diversity
Authors: Vollmer Sebastian , Laillou Arnaud , Albers Nora , Nanama Simeon
Published: January 2025

Objective:

The aim of this study is to analyse complementary feeding practices, to assess the extent to which minimum dietary diversity (MDD) recommendations are being met in the population studied and to study factors that influence the achievement of MDD.

Design:

We pooled individual level data form the Demographic and Health Surveys (DHS) and Multi Indicator Cluster Surveys (MICS). We apply methods from poverty measurement to identify individual gaps towards achieving MDD. We further identify food groups that separate children who achieve MDD from those who do not.

Setting:

West and Central Africa.

Participants:

62 257 children aged between 6 and 23 months.

Results:

82·0 per cent of children do not achieve MDD and on average are lacking 2·5 out of five required food groups. For 19·0 per cent of children, the gap to MDD is one food group and for 23·7 per cent of children the gap is two food groups. Consumption of eggs, other fruits and vegetables as well as legumes and nuts is particularly low among children who are not achieving MDD. More than 90·0 per cent of children who do not achieve MDD do not consume these food groups compared to around half of children who achieve MDD.

Conclusions:

Overall MDD is low, but there is large potential for improving MDD achievement if food consumption can be increased by one or two food groups. Available, affordable and culturally accepted food groups are identified that could be prioritised in interventions to close this gap.
Morphological and chemical characteristics of Fritillaria species: species differentiation through morphometric measurements and GC-MS analysis
Authors: Şentürk Bengisu , Aytar Erdi Can , Durmaz Alper , İşler Sinan , Deniz İsmail Gökhan , Özdener Kömpe Yasemin
Published: January 2025

This study examines the morphological and chemical characteristics of seeds from five Fritillaria species: Fritillaria pinardii, Fritillaria pontica, Fritillaria kittaniae, Fritillaria imperialis and Fritillaria alfredae Post subsp. glaucoviridis (Turrill) Rix. Morphological measurements included total length, total width, embryo length, embryo width, seed left-wing coverage width, seed right-wing coverage width and the distance between crossing points. These measurements revealed significant differences among the species. For example, F. imperialis exhibited the longest seeds and the largest embryos, while F. alfredae Post subsp. glaucoviridis had the smallest dimensions. Chemical analyses were conducted using gas chromatography-mass spectrometry, identifying various significant compounds across the species. High proportions of 2,2-dimethoxybutane were found in the seed samples. In F. pontica, compounds such as 2,2-dimethoxybutane (66.33%) and 1,1-dipropoxypropane (13.24%) were prevalent. Fritillaria kittaniae seeds showed high levels of benzene, 1,1′-(3,3-dimethyl-1-butenylidene) bis- (25.57%) and cyclohexene, 3-methyl-6-(1-methylethylidene)- (6.89%). In F. imperialis, significant compounds included 1,3-dioxolane-4-methanol, 2-ethyl-2-methyl (9.73%) and dodecane (5.73%). Fritillaria pinardii had notable amounts of 3,6-dimethyloctane (4.81%), while F. alfredae subsp. glaucoviridis contained 2-methoxyethyl(trimethyl)silane (13.21%). Principal component analysis and cluster analysis revealed clear groupings based on morphological and chemical similarities. Fritillaria pinardii, F. pontica and F. kittaniae formed a cluster due to their similar morphological and chemical characteristics, whereas F. imperialis and F. alfredae subsp. glaucoviridis formed a distinct group. These findings provide valuable insights into the identification and classification of Fritillaria species. Integrating morphological and chemical data can enhance the accurate identification of these species. This study contributes to understanding the natural diversity of Fritillaria species and has implications for ecological studies.
Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions
Authors: Shao Chang , Tang Shuo , Yu Siqin , Liu Chenguang , Zhang Yueyang , Wan Tianyan , He Zimeng , Yuan Qi , Wu Shihan , Zhang Hanqing , Wan Ning , Zhan Mengru , Tan Ren Xiang , Hao Haiping , Ye Hui , Wang Nanxi
Published: January 2025

Protein lactylation is an emerging field. To advance the exploration of its biological functions, here we develop a comprehensive workflow that integrates proteomics to identify lactylated sites, genetic code expansion (GCE) for the expression of site-specifically lactylated proteins in living cells, and an integrated functional analysis (IFA) platform to evaluate their biological effects. Using a combined wet-and-dry-lab proteomics strategy, we identify a conserved lactylation at ALDOA-K147, which we hypothesize plays a significant biological role. Expression of this site-specifically lactylated ALDOA in mammalian cells reveals that this modification not only inhibits enzymatic activity but also induces gain-of-function effects. These effects reshaped ALDOA functionality by enhancing protein stability, promoting nuclear translocation, regulating adhesion-related gene expression, altering cell morphology and modulating ALDOA-interacting proteins. Our findings highlight the utility of the GCE-based workflow in establishing causal relationships between specific lactylation events and both target-specific and cell-wide changes, advancing our understanding of protein lactylation’s functional impact.
Three-dimensional architecture and linearized mapping of vibrissa follicle afferents
Authors: Gerhardt Ben , Alfken Jette , Reichmann Jakob , Salditt Tim , Brecht Michael
Published: January 2025

Understanding vibrissal transduction has advanced by serial sectioning and identified afferent recordings, but afferent mapping onto the complex, encapsulated follicle remains unclear. Here, we reveal male rat C2 vibrissa follicle innervation through synchrotron X-ray phase contrast tomograms. Morphological analysis identified 5% superficial, ~32 % unmyelinated and 63% myelinated deep vibrissal nerve axons. Myelinated afferents consist of each one third Merkel and club-like, and one sixth Ruffini-like and lanceolate endings. Unsupervised clustering of afferent properties aligns with classic morphological categories and revealed previously unrecognized club-like afferent subtypes distinct in axon diameter and Ranvier internode distance. Myelination and axon diameters indicate a proximal-to-distal axon-velocity gradient along the follicle. Axons innervate preferentially dorso-caudally to the vibrissa, presumably to sample contacts from vibrissa protraction. Afferents organize in axon-arms innervating discrete angular territories. The radial axon-arm arrangement around the vibrissa maps into a linear representation of axon-arm bands in the nerve. Such follicle linearization presumably instructs downstream linear brainstem barrelettes. Synchrotron imaging provides a synopsis of afferents and mechanotransductory machinery.
A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD
Authors: McCallister Tristan X. , Lim Colin K. W. , Singh Mayuri , Zhang Sijia , Ahsan Najah S. , Terpstra William M. , Xiong Alisha Y. , Zeballos C M. Alejandra , Powell Jackson E. , Drnevich Jenny , Kang Yifei , Gaj Thomas
Published: January 2025

An abnormal expansion of a GGGGCC (G4C2) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the G4C2 repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits. This high-fidelity system possessed improved transcriptome-wide specificity compared to its native form and mediated targeting in motor neuron-like cells derived from a patient with ALS. These results lay the foundation for the implementation of RNA-targeting CRISPR technologies for C9ORF72-linked ALS/FTD.
Structure and catalytic activity of the SAM-utilizing ribozyme SAMURI
Authors: Chen Hsuan-Ai , Okuda Takumi , Lenz Ann-Kathrin , Scheitl Carolin P. M. , Schindelin Hermann , Höbartner Claudia
Published: January 2025

Ribozymes that catalyze site-specific RNA modification have recently gained increasing interest for their ability to mimic methyltransferase enzymes and for their application to install molecular tags. Recently, we reported SAMURI as a site-specific alkyltransferase ribozyme using S-adenosylmethionine (SAM) or a stabilized analog to transfer a methyl or propargyl group to N3 of an adenosine. Here, we report the crystal structures of SAMURI in the postcatalytic state. The structures reveal a three-helix junction with the catalytic core folded into four stacked layers, harboring the cofactor and the modified nucleotide. Detailed structure–activity analyses explain the cofactor scope and the structural basis for site selectivity. A structural comparison of SAMURI with SAM riboswitches sheds light on how the synthetic ribozyme overcomes the strategies of natural riboswitches to avoid self-methylation. Our results suggest that SAM and its analogs may serve as substrates for various RNA-catalyzed reactions, for which the corresponding ribozymes remain to be identified.
China’s product-level CO2 emissions dataset aligned with national input-output tables from 1997 to 2020
Authors: Li Xinbei , Liu Yu , Zhang Jing , Zhou Meifang , Meng Bo
Published: January 2025

Carbon emission research based on input-output tables (IOTs) has received attention, but data quality issues persist due to inconsistencies between the sectoral scopes of energy statistics and IOTs. Specifically, China’s official energy data are reported at the industry level, whereas IOTs are organized by product sectors. Valid IOT-based environmental models require consistent transformation from industry-level to product-level emissions. However, most existing studies overlook this necessary transformation, leading to substantial estimation errors. This study addresses this issue by developing a high-quality, product-level emissions dataset for China, grounded in robust product technology identification derived from IOTs. Our new emissions dataset, aligned with Chinese national IOTs, covers 29 to 34 product sectors across 7 benchmark years from 1997 to 2020. It includes data from 4 to 5 energy sectors and detailed emissions for 18 types of fossil fuels, using both IPCC-default and two China-specific emission factors. This inventory improves product-sector emission accounting and can be integrated into IOT-based climate and energy models, serving as a fundamental database for energy and emission analysis.
Forearm elevation impairs local static handgrip endurance likely through reduction in vascular conductance and perfusion pressure: revisiting Rohmert’s curve
Authors: Heinzl L. , Risse S. , Schwarzbach H. , Hildebrandt O. , Koehler U. , Koenig A. M. , Mahnken A. H. , Kinscherf R. , Hildebrandt W.
Published: January 2025

Maximal isometric contraction time (MICT) is critical for most motor tasks and depends on skeletal muscle blood flow at < 40% of maximal voluntary strength (MVC). Whether limb work positions associated with reduced perfusion pressure and facilitated vessel compression affect MICT is largely unknown. In 14 healthy young men we therefore assessed bilateral handgrip MICT at 15, 20, 30, 40, and 70% of MVC in horizontal forearm positions of 0.0, + 27.5 or − 27.5 cm relative to heart level. Forearm blood flow (FBF, venous occlusion plethysmography) and brachial blood pressure were measured repetitively. MICT at 15% MVC was significantly shorter by 66.3 and 86.2 s with forearm position + 27.5 cm (389.6 ± 23.3 s) as compared to 0.0 cm (455.9 ± 34.1 s) and − 27.5 cm (475.8 ± 35.0 s) while MICT at 20–70% MVC was unaffected. Peak FBF at 15% MVC was significantly lower in position + 27.5 cm (11.11 ± 0.92 ml/min/100 ml) compared to 0.0 cm (15.55 ± 0.91 ml/min/100 ml) or − 27.5 cm (14.21 ± 0.59 ml/min/100 ml) and vascular resistance significantly higher in position + 27.5 vs 0.0 or − 27.5 cm. Working position above, but not below heart level may limit MICT at 15% MVC possibly through blood flow reduction arising from increased vascular resistance beside reduced perfusion pressure. Local isometric endurance warrants (re)evaluation regarding hydrostatic/gravitational or other hemodynamic limitations.
The non-nutritive sweetener rebaudioside a enhances phage infectivity
Authors: Marongiu Luigi , Brzozowska Ewa , Brykała Jan , Burkard Markus , Schmidt Herbert , Szermer-Olearnik Bożena , Venturelli Sascha
Published: January 2025

Non-nutritive sweeteners (NNS) are widely employed in foodstuffs. However, it has become increasingly evident that their consumption is associated with bacterial dysbiosis, which, in turn, is linked to several health conditions, including a higher risk of type 2 diabetes and cancer. Among the NNS, stevia, whose main component is rebaudioside A (rebA), is gaining popularity in the organic food market segment. While the effect of NNS on bacteria has been established, the impact of these sweeteners on bacterial viruses (phages) has been neglected, even though phages are crucial elements in maintaining microbial eubiosis. The present study sought to provide a proof-of-concept of the impact of NNS on phage infectivity by assessing the binding of rebA to phage proteins involved in the infection process of enteropathogenic bacteria, namely the fiber protein gp17 of Yersinia enterocolitica phage φYeO3-12 and the tubular baseplate protein gp31 of Klebsiella pneumoniae phage 32. We employed docking analysis and a panel of in vitro confirmatory tests (microscale thermophoresis, RedStarch™ depolymerization, adsorption, and lysis rates). Docking analysis indicated that NNS can bind to both fiber and baseplate proteins. Confirmatory assays demonstrated that rebA can bind gp31 and that such binding increased the protein’s enzymatic activity. Moreover, the binding of rebA to gp17 resulted in a decrease in the adsorption rate of the recombinant protein to its host but increased the Yersinia bacteriolysis caused by the whole phage compared to unexposed controls. These results support the hypothesis that NNS can impair phage infectivity, albeit the resulting effect on the microbiome remains to be elucidated.
Otolith chemistry suggests population heterogeneity within a genetically homogeneous Indian scad population along Indian coast
Authors: Jose Anjaly , Sukumaran Sandhya , Raj Neenu , Nisha K. , Varghese Eldho , Laly S. J. , Panda Satyen Kumar , Roul Subal Kumar , Azeez P. Abdul , Kizhakudan Shoba Joe , Gopalakrishnan A.
Published: January 2025

The Indian scad, Decapterus russelli is one of the most exploited pelagic resources of India. Population genetic analyses using mitochondrial and nuclear markers indicated a lack of genetic structuring among populations from Indian waters. As this species is highly migratory, it is also important to establish the environmental influence on its population structure. In the present study, the whole sagittal otolith composition was analysed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) to assess spatial distribution of D. russelli collected from 4 sites along the Indian coast. Elemental ratios (Ba/Ca, Fe/Ca, K/Ca, Mg/Ca, Na/Ca, Sr/Ca and Zn/Ca) were analysed using univariate and multivariate statistics to determine whether this chemical signature can provide insight into the adaptive patterns. All element/Ca ratios are found to be significantly different between the four sampling locations (ANOVA, p < 0.05; MANOVA, p < 0.05). Five of the element/Ca ratios were found to be significantly different when the data was analysed coastwise (ANOVA, p < 0.05; MANOVA, p < 0.05). The LDA plot also showed the spatial heterogeneity of Element/Ca ratios between the four sampling sites, but some overlaps were also observed, reflecting the migratory ability of the species. This basic information on spatial ecology is required for formulating effective management and conservation strategies for the species.
The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAB receptors under ischemic conditions by inhibiting fast receptor recycling
Authors: Bhat Musadiq A. , Hleihil Mohammad , Mondéjar Irene , Grampp Thomas , Benke Dietmar
Published: January 2025

GABAB receptors mediate prolonged inhibition in the brain and are important for keeping neuronal excitation and inhibition in a healthy balance. However, under excitotoxic/ischemic conditions, GABAB receptors are downregulated by dysregulated endocytic trafficking and can no longer counteract the severely enhanced excitation, eventually triggering neuronal death. Recently, we developed interfering peptides targeting protein-protein interactions involved in downregulating the receptors. Treatment with these peptides restored GABAB receptor expression after an ischemic insult and thereby inhibited neuronal overexcitation and progressive neuronal death. In this study, we searched for GABAB receptor interactions that specifically occur under ischemic conditions. We found that the E3 ubiquitin ligase MARCH1 is specifically upregulated under ischemic/excitotoxic conditions. Upregulated MARCH1 interacts with GABAB receptors and triggered downregulation of plasma membrane GABAB receptors by inhibiting fast recycling of the receptors. We developed an interfering peptide that inhibits the MARCH1/GABAB receptor interaction. Treatment of cultured neurons subjected to ischemic stress with this peptide restored receptor expression and as a consequence stopped progressive neuronal death. Thus, inhibiting the interaction of GABAB receptors with MARCH1 to restore cell surface receptor expression might be a promising strategy to prevent progressive neuronal death induced by ischemic conditions.
A hybrid machine learning approach for the personalized prognostication of aggressive skin cancers
Authors: Andrew Tom W. , Alrawi Mogdad , Plummer Ruth , Reynolds Nick , Sondak Vern , Brownell Isaac , Lovat Penny E. , Rose Aidan , Shalhout Sophia Z.
Published: January 2025

Accurate prognostication guides optimal clinical management in skin cancer. Merkel cell carcinoma (MCC) is the most aggressive form of skin cancer that often presents in advanced stages and is associated with poor survival rates. There are no personalized prognostic tools in use in MCC. We employed explainability analysis to reveal new insights into mortality risk factors for this highly aggressive cancer. We then combined deep learning feature selection with a modified XGBoost framework, to develop a web-based prognostic tool for MCC termed ‘DeepMerkel’. DeepMerkel can make accurate personalised, time-dependent survival predictions for MCC from readily available clinical information. It demonstrated generalizability through high predictive performance in an international clinical cohort, out-performing current population-based prognostic staging systems. MCC and DeepMerkel provide the exemplar model of personalised machine learning prognostic tools in aggressive skin cancers.
Second harmonic generation imaging reveals entanglement of collagen fibers in the elephant trunk skin dermis
Authors: Schulz Andrew K. , Plotczyk Magdalena , Sordilla Sophia , Gaboriau David C. A. , Boyle Madeline , Singal Krishma , Reidenberg Joy S. , Hu David L. , Higgins Claire A.
Published: January 2025

Form-function relationships often have tradeoffs: if a material is tough, it is often inflexible, and vice versa. This is particularly relevant for the elephant trunk, where the skin should be protective yet elastic. To investigate how this is achieved, we used classical histochemical staining and second harmonic generation microscopy to describe the morphology and composition of elephant trunk skin. We report structure at the macro and micro scales, from the thickness of the dermis to the interaction of 10 μm thick collagen fibers. We analyzed several sites along the length of the trunk to compare and contrast the dorsal-ventral and proximal-distal skin morphologies and compositions. We find the dorsal skin of the elephant trunk can have keratin armor layers over 2 mm thick, which is nearly 100 times the thickness of the equivalent layer in human skin. We also found that the structural support layer (the dermis) of the elephant trunk contains a distribution of collagen-I (COL1) fibers in both perpendicular and parallel arrangement. The bimodal distribution of collagen is seen across all portions of the trunk, and is dissimilar from that of human skin where one orientation dominates within a body site. We hypothesize that this distribution of COL1 in the elephant trunk allows both flexibility and load-bearing capabilities. Additionally, when viewing individual fiber interactions of 10 μm thick collagen, we find the fiber crossings per unit volume are five times more common than in human skin, suggesting that the fibers are entangled. We surmise that these intriguing structures permit both flexibility and strength in the elephant trunk. The complex nature of the elephant skin may inspire the design of materials that can combine strength and flexibility.
The Amazonian mangrove systems accumulate and release dissolved neodymium and hafnium to the oceans
Authors: Xu Antao , Hathorne Ed , Seidel Michael , Liu Te , Asp Nils E. , Koschinsky Andrea , Dittmar Thorsten , Frank Martin
Published: January 2025

Mangroves are essential tropical ecosystems nurturing a wide range of marine biodiversity and counteracting global warming by sequestering atmospheric carbon dioxide. Hence, the export mechanisms and fluxes of particulate and dissolved organic carbon and trace elements from mangroves directly influence coastal productivity, the global carbon cycle and thus global climate, which are, however, not well constrained. Here we find consistent radiogenic neodymium and hafnium isotopic compositions of porewater, sedimentary iron-manganese oxyhydroxides and coastal seawater, suggesting that the Amazonian mangrove belt supplies trace elements through porewater discharge, dissolution of iron-manganese oxyhydroxides and their interactions with seawater. Together, these processes supply 8.4 × 106 g yr-1 dissolved neodymium, equivalent to 64% of the total sources of neodymium to the Amazonian coastal seawater. Globally, mangrove systems along the continental margins contribute 6–9% of the net neodymium input to the ocean, which is similar to the contributions from atmospheric deposition. A contribution of this magnitude is potentially also the case for other trace elements, given the strong correlations between neodymium and iron (Pearson r = 0.92), and manganese (r = 0.75) concentrations across the entire river-ocean section, emphasizing the crucial role of mangrove system inputs in micro-nutrient cycling.