bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating dopaminergic abnormalities in schizophrenia and first-episode psychosis with normative modelling and multisite molecular neuroimaging
Authors: Giacomel Alessio , Martins Daniel , Nordio Giovanna , Easmin Rubaida , Howes Oliver , Selvaggi Pierluigi , Williams Steven C. R. , Turkheimer Federico , De Groot Marius , Dipasquale Ottavia , Veronese Mattia ,   the FDOPA PET imaging working group, Angelescu Ilinca , Bloomfield Micheal , Bonoldi Ilaria , Borgan Faith , Dahoun Tarik , D’Ambrosio Enrico , Demjaha Arsime , Donocik Jecek , Egerton Alice , Kaar Stephen , Kim Euitae , Kim Seoyoung , Maccabe James , Matthews Julian , McCutcheon Robert , McGuire Philip , Nosarti Chiara , Nour Matthew , Rogdaki Maria , Rutigliano Grazia , Talbot Peter S. , Vano Luke 
Published: February 2025

Abstract
Molecular neuroimaging techniques, like PET and SPECT, offer invaluable insights into the brain’s in-vivo biology and its dysfunction in neuropsychiatric patients. However, the transition of molecular neuroimaging into diagnostics and precision medicine has been limited to a few clinical applications, hindered by issues like practical feasibility, high costs, and high between-subject heterogeneity of neuroimaging measures. In this study, we explore the use of normative modelling (NM) to identify individual patient alterations by describing the physiological variability of molecular functions. NM potentially addresses challenges such as small sample sizes and diverse acquisition protocols typical of molecular neuroimaging studies. We applied NM to two PET radiotracers targeting the dopaminergic system ([11C]-(+)-PHNO and [18F]FDOPA) to create a reference-cohort model of healthy controls. The models were subsequently utilized on different independent cohorts of patients with psychosis in different disease stages and treatment outcomes. Our results showed that patients with psychosis exhibited a higher degree of extreme deviations (~3-fold increase) than controls, although this pattern was heterogeneous, with minimal overlap of extreme deviations topology (max 20%). We also confirmed that striatal [18F]FDOPA signal, when referenced to a normative distribution, can predict treatment response (striatal AUC ROC: 0.77–0.83). In conclusion, our results indicate that normative modelling can be effectively applied to molecular neuroimaging after proper harmonization, enabling insights into disease mechanisms and advancing precision medicine. In addition, the method is valuable in understanding the heterogeneity of patient populations and can contribute to maximising cost efficiency in studies aimed at comparing cases and controls.
A new module in the drug development process: preclinical multi-center randomized controlled trial of R-ketamine on alcohol relapse
Authors: Meinhardt Marcus W. , Skorodumov Ivan , Jeanblanc Jérôme , Benvenuti Federica , Hilal Fahd François , Domi Esi , André Camille , Bodeau Sandra , Jeanblanc Virginie , Domanegg Kevin , Ciccocioppo Roberto , Naassila Mickael , Spanagel Rainer 
Published: February 2025

Abstract
The drug development process in psychiatry faces significant challenges due to low reproducibility rates in animal testing, which often leads to translation failures. To address this issue, we introduce a new approach in psychiatric drug development: a preclinical randomized controlled trial (preRCT). To demonstrate its potential utility, we conducted a multi-center preRCT using the alcohol deprivation effect (ADE) model to assess the impact of ketamine and R-ketamine on alcohol relapse across three European research centers. Ketamine (20 mg/kg) significantly reduced relapse, while R-ketamine showed efficacy only in females. A higher dose of R-ketamine (40 mg/kg) was also effective in males. These sex-dependent effects were linked to plasma R-ketamine levels, which were two-fold higher in female compared to male rats. Notably, R-ketamine demonstrated a lasting reduction in alcohol consumption without adverse effects. In conclusion, our preRCT demonstrates R-ketamine’s effectiveness in reducing alcohol relapse and supports translation to a clinical RCT that accounts for sex-dependent effects.
Overview of statistics teaching within undergraduate programmes in UK and Ireland dental schools
Authors: Leary Sam , Cook Neil , Kang Jing 
Published: February 2025

Abstract

Introduction The United Kingdom (UK) General Dental Council's (GDC's) learning outcomes for undergraduate dental students briefly mention critical appraisal but not statistics. Hence, wide variation in statistics teaching across the dental schools is likely but has not yet been well-documented.

Methods A survey was conducted to capture the main features of each of the dental degrees in the 18 UK and Ireland dental schools in terms of statistics-related (standalone or as part of other courses/modules) teaching.

Results Representatives from all 18 dental schools completed the survey. There were some similarities, such as most using teaching materials specifically developed for their school, and aiming to teach students to understand/interpret but not generate statistics. However, the number/type of staff delivering the teaching, student contact hours, number of statistical concepts taught, whether statistical theory/formulae/packages were used and inclusion in summative assessments varied extensively. Most reported that this teaching was negatively perceived by the students and many felt that changes were needed.

Discussion and conclusion This comprehensive review of undergraduate dental statistics-related provision allows dental schools to compare and contrast their own teaching, which is very timely given the imminent need to implement a new GDC framework. Guidelines to encourage more standardised teaching should be developed to improve the ability of newly qualified dentists to practise evidence-based dentistry.
Deubiquitination enzyme USP35 negatively regulates MAVS signaling to inhibit anti-tumor immunity
Authors: Zhang Heping , Zhu Jiali , He Rong , Xu Lin , Chen Yunfei , Yu Haihong , Sun Xuejiao , Wan Shengpeng , Yin Xiaolan , Liu Yu’e , Gao Jie , Li Yue , Li Zhixiong , Lu Yi , Xu Qing 
Published: February 2025

Abstract
The RIG-I/MAVS signaling stimulates anti-tumor immunity by triggering the production of inflammatory cytokines. Activation of MAVS induced by viral RNA and RIG-I binding is critical in this pathway. However, the molecular mechanism underlying the regulation of MAVS activity and its function in anti-tumor immunity is not fully understood. Here, we report that the ubiquitin-specific protease 35 (USP35) negatively regulates the MAVS signaling. Mechanistically, USP35 interacts with MAVS and removes its K63-linked polyubiquitin chains, thereby inhibiting viral-induced MAVS-TBK1-IRF3 activation and downstream inflammatory gene expression. Importantly, depletion of USP35 significantly enhances the anti-tumor immunity and synergizes with oncolytic virotherapy to suppress xenograft tumor growth of melanoma cells. Thus, our study identifies USP35 as a negative regulator of MAVS signaling, representing a potential immunosuppressive factor in cutaneous melanoma.
In-frame deletion variant of ABCD1 in a sporadic case of adrenoleukodystrophy
Authors: Matsukawa Takashi , Sudo Atsushi , Kakumoto Toshiyuki , Hao Akihito , Kainaga Mitsuhiro , Chang Hyangri , Mano Tatsuo , Ishiura Hiroyuki , Mitsui Jun , Hayashi Toshihiro , Morishita Shinichi , Tsuji Shoji , Toda Tatsushi 
Published: February 2025

Abstract
Adrenoleukodystrophy (ALD), an X-linked leukodystrophy caused by pathogenic variants in ABCD1, exhibits a broad range of phenotypes from childhood-onset cerebral forms to adult-onset adrenomyeloneuropathy (AMN). We report a rare in-frame ABCD1 deletion c.1469_71delTGG (p.Val490del) in a man with AMN. Although this variant has been interpreted as ‘uncertain significance’ in ClinVar, biochemical analysis along with clinical evaluation confirmed the pathogenicity of this variant, underscoring the importance of functional assessment of in-frame deletions.
Associations of PFAS and OH-PCBs with risk of multiple sclerosis onset and disability worsening
Authors: Vaivade Aina , Erngren Ida , Carlsson Henrik , Freyhult Eva , Emami Khoonsari Payam , Noui Yassine , Al-Grety Asma , Åkerfeldt Torbjörn , Spjuth Ola , Gallo Valentina , Larsson Anders Olof , Kockum Ingrid , Hedström Anna Karin , Alfredsson Lars , Olsson Tomas , Burman Joachim , Kultima Kim 
Published: February 2025

Abstract
Exposure to per- and polyfluorinated substances (PFAS) and hydroxylated polychlorinated biphenyls (OH-PCBs) is associated with adverse human health effects, including immunosuppression. It is unknown if these substances can affect the course of autoimmune diseases. This study was based on 907 individuals with multiple sclerosis (MS) and 907 matched controls, where the MS cases were followed longitudinally using the Swedish MS register. We demonstrate sex- and disease-specific differences in serum PFAS concentrations between individuals with MS and controls. Moreover, two OH-PCBs (4-OH-CB187 and 3-OH-CB153) are associated with an increased risk of developing multiple sclerosis, regardless of sex and immigration status. With a clinical follow-up time of up to 18 years, an increase in serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA) decreases the risk of confirmed disability worsening in both sexes, as well as perfluoroheptanesulfonic acid (PFHpS) and perfluorononanoic acid (PFNA), only in males with MS. These results show previously unknown associations between OH-PCBs and the risk of developing MS, as well as the inverse associations between PFAS exposure and the risk of disability worsening in MS.
Remodeling of lipid-foam prototissues by network-wide tension fluctuations induced by active particles
Authors: Gu Andre A. , Uçar Mehmet Can , Tran Peter , Prindle Arthur , Kamat Neha P. , Steinkühler Jan 
Published: February 2025

Abstract
Recent advances in the field of bottom-up synthetic biology have led to the development of synthetic cells that mimic some features of real cells, such as division, protein synthesis, or DNA replication. Larger assemblies of synthetic cells may be used to form prototissues. However, existing prototissues are limited by their relatively small lateral dimensions or their lack of remodeling ability. Here, we introduce a lipid-based tissue mimetic that can be easily prepared and functionalized, consisting of a millimeter-sized “lipid-foam” with individual micrometer-sized compartments bound by lipid bilayers. We characterize the structural and mechanical properties of the lipid-foam tissue mimetic, and we demonstrate self-healing capabilities enabled by the fluidity of the lipid bilayers. Upon inclusion of bacteria in the tissue compartments, we observe that the tissue mimetic exhibits network-wide tension fluctuations driven by membrane tension generation by the swimming bacteria. Active tension fluctuations facilitate the fluidization and reorganization of the prototissue, providing a versatile platform for understanding and mimicking biological tissues.
Ethylene promotes SMAX1 accumulation to inhibit arbuscular mycorrhiza symbiosis
Authors: Das Debatosh , Varshney Kartikye , Ogawa Satoshi , Torabi Salar , Hüttl Regine , Nelson David C. , Gutjahr Caroline 
Published: February 2025

Abstract
Most land plants engage in arbuscular mycorrhiza (AM) symbiosis with Glomeromycotina fungi for better access to mineral nutrients. The plant hormone ethylene suppresses AM development, but a molecular explanation for this phenomenon is lacking. Here we show that ethylene inhibits the expression of many genes required for AM formation in Lotus japonicus. These genes include strigolactone biosynthesis genes, which are needed for fungal activation, and Common Symbiosis genes, which are required for fungal entry into the root. Application of strigolactone analogs and ectopic expression of the Common Symbiosis gene Calcium Calmodulin-dependent Kinase (CCaMK) counteracts the effect of ethylene. Therefore, ethylene likely inhibits AM development by suppressing expression of these genes rather than by inducing defense responses. These same genes are regulated by SUPPRESSOR OF MAX2 1 (SMAX1), a transcriptional repressor that is proteolyzed during karrikin signaling. SMAX1 is required for suppression of AM by ethylene, and SMAX1 abundance in nuclei increases after ethylene application. We conclude that ethylene suppresses AM by promoting accumulation of SMAX1. SMAX1 emerges as a signaling hub that integrates karrikin and ethylene signaling, thereby orchestrating development of a major plant symbiosis with a plant’s physiological state.
Advancing nonadiabatic molecular dynamics simulations in solids with E(3) equivariant deep neural hamiltonians
Authors: Zhang Changwei , Zhong Yang , Tao Zhi-Guo , Qin Xinming , Shang Honghui , Lan Zhenggang , Prezhdo Oleg V. , Gong Xin-Gao , Chu Weibin , Xiang Hongjun 
Published: February 2025

Abstract
Non-adiabatic molecular dynamics (NAMD) simulations have become an indispensable tool for investigating excited-state dynamics in solids. In this work, we propose a general framework, N2AMD (Neural-Network Non-Adiabatic Molecular Dynamics), which employs an E(3)-equivariant deep neural Hamiltonian to boost the accuracy and efficiency of NAMD simulations. Distinct from conventional machine learning methods that predict key quantities in NAMD, N2AMD computes these quantities directly with a deep neural Hamiltonian, ensuring excellent accuracy, efficiency, and consistency. N2AMD not only achieves impressive efficiency in performing NAMD simulations at the hybrid functional level within the framework of the classical path approximation (CPA), but also demonstrates great potential in predicting non-adiabatic coupling vectors and suggests a method to go beyond CPA. Furthermore, N2AMD demonstrates excellent generalizability and enables seamless integration with advanced NAMD techniques and infrastructures. Taking several extensively investigated semiconductors as the prototypical system, we successfully simulate carrier recombination in both pristine and defective systems at large scales where conventional NAMD often significantly underestimates or even qualitatively incorrectly predicts lifetimes. This framework offers a reliable and efficient approach for conducting accurate NAMD simulations across various condensed materials.
No evidence of positive causal effects of maternal and paternal age at first birth on children’s test scores at age 10 years
Authors: Grätz Michael , Tropf Felix C. , Torvik Fartein Ask , Andreassen Ole A. , Lyngstad Torkild H. 
Published: February 2025

Abstract
Research has shown that higher maternal and paternal age is positively associated with children’s education. Debate continues as to whether these relationships are causal. This is of great interest given the postponement of first births in almost all developed countries during the twentieth century. Here we use an instrumental variable approach (Mendelian randomization) using maternal and paternal polygenic indices (PGIs) for age at first birth—while conditioning on the child’s PGI for age at first birth—to identify the causal effects of maternal and paternal age at first birth on children’s test scores based on data from the Norwegian Mother, Father and Child Cohort study. We do not find evidence of positive causal effects of both maternal and paternal age at first birth on children’s test scores at age 10 years once the children’s PGI and correlations among different PGIs are controlled for. We therefore conclude that our results do not provide evidence in favour of sociological theories that predict positive causal effects of parental age on children’s educational attainment.
Mechanochemical bistability of intestinal organoids enables robust morphogenesis
Authors: Xue Shi-Lei , Yang Qiutan , Liberali Prisca , Hannezo Edouard 
Published: February 2025

Abstract
Reproducible pattern and form generation during embryogenesis is poorly understood. Intestinal organoid morphogenesis involves a number of mechanochemical regulators such as cell-type-specific cytoskeletal forces and osmotically driven lumen volume changes. It is unclear how these forces are coordinated in time and space to ensure robust morphogenesis. Here we show how mechanosensitive feedback on cytoskeletal tension gives rise to morphological bistability in a minimal model of organoid morphogenesis. In the model, lumen volume changes can impact the epithelial shape via both direct mechanical and indirect mechanosensitive mechanisms. We find that both bulged and budded crypt states are possible and dependent on the history of volume changes. We test key modelling assumptions via biophysical and pharmacological experiments to demonstrate how bistability can explain experimental observations, such as the importance of the timing of lumen shrinkage and robustness of the final morphogenetic state to mechanical perturbations. This suggests that bistability arising from feedback between cellular tensions and fluid pressure could be a general mechanism that coordinates multicellular shape changes in developing systems.
A curated soil fungal dataset to advance fungal ecology and conservation research in Australia and Antarctica
Authors: Florence Luke , Tomlinson Sean , Freestone Marc , Morgan John W. , Wood Jennifer L. , Truong Camille 
Published: February 2025

Abstract
DNA metabarcoding has played a pivotal role in advancing our understanding of the diversity and function of soil-inhabiting fungi. The Australian Microbiome Initiative has produced an extensive soil fungal metabarcoding dataset of more than 2000 plots across a breadth of ecosystems in Australia and Antarctica. Sequence data requires rigorous approaches for the integration of species occurrences into biodiversity platforms, addressing biases due to false positives or overinflated diversity estimates, among others. To tackle such biases, we conducted a rigorous analysis of the fungal dataset following best practices in fungal metabarcoding and integrated it with over 100 predictor variables to fast-track data exploration. We carefully validated our methodology based on studies conducted on historical versions of the dataset. Our approach generated robust information on Australian soil fungi that can be leveraged by end-users interested in biodiversity, biogeography, and conservation. This novel resource will unlock new frontiers in soil fungal research within the Southern Hemisphere and beyond.
Theoretical analysis of dynamic sliding mechanism of rock slope with a bedding structural plane based on stress wave propagation
Authors: Chai Shaobo , Song Boyang , Liu Jinhao , Liu Kai , Liu Xinyuan , Shi Jiehui 
Published: February 2025

Abstract
The stress at the structural plane of bedding rock slope will change under dynamic load, which may lead to sliding failure risk of the slope. Based on the time-domain recursive method (TDRM), the propagation process of stress waves in viscoelastic rock slope with a nonlinear bedding plane is analyzed, and the propagation equation of multiple reflected waves between the plane and the slope surface is obtained. According to the superposition principle and the relation between the particle vibration velocity caused by stress waves and stress, the expressions of normal and tangential stress of any particle at the structural plane are obtained. Furthermore, in light of the gravitational impact on the rock mass, we formulate the slip criterion equation for the structural plane. The results indicate that the stress field at the structural plane is influenced by several factors, including the slope angle, horizontal positioning of monitoring points, vertical distance to the slope foot, and the initial stiffness of the structural plane. The influence of multiple reflected waves on stress field obviously increases the possibility of rock mass sliding on structural plane. This paper theoretically elucidates the slippage mechanism of a rock slope featuring a bedding structural plane subjected to the effects of stress wave. The research findings furnish a theoretical foundation for comprehending the dynamic response of rock slopes, conducting dynamic stability analyses, and ensuring the safety measures for rock mass engineering projects.
Single-molecule measurements of bacteriophage lambda DNA packaging using purified terminase motor proteins and E. coli integration host factor
Authors: Rawson Brandon , Yang Qin , Catalano Carlos E. , Smith Douglas E. 
Published: February 2025

Abstract
Biomotor-driven DNA packaging is a key step in the life cycle of many viruses. We previously developed single-molecule methods using optical tweezers to measure packaging dynamics of the bacteriophage lambda motor. The lambda system is more complex than others examined via single-molecule assays with respect to the packaging substrate and ancillary proteins required. Because of this, previous studies which efficiently detected packaging events used crude E. coli cell extracts containing host factors and the terminase packaging enzyme. However, use of extracts is suboptimal for biochemical manipulation and obfuscates interrogation of additional factors that affect the process. Here we describe an optical tweezers assay using purified lambda terminase holoenzyme. Packaging events are as efficient as with crude extracts, but only if purified E. coli integration host factor (IHF) is included in the motor assembly reactions. We find that the ATP-driven DNA translocation dynamics, motor force generation, and motor-DNA interactions without nucleotide are virtually identical to those measured with extracts. Thus, single-molecule packaging activity can be fully recapitulated in a minimal system containing only purified lambda procapsids, purified terminase, IHF, and ATP. This sets the stage for single-molecule studies to investigate additional phage proteins known to play essential roles in the packaging reaction.