bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiverse Analysis
Authors: Young Cristobal , Cumberworth Erin
Published: February 2025

There are many ways of conducting an analysis, but most studies show only a few carefully curated estimates. Applied research involves a complex array of analytical decisions, often leading to a 'garden of forking paths' where each choice can lead to different results. By systematically exploring how alternative analytical choices affect the findings, Multiverse Analysis reveals the full range of estimates that the data can support and uncovers insights that single-path analyses often miss. It shows which modelling decisions are most critical to the results and reveals how data and assumptions work together to produce empirical estimates. Focusing on intuitive understanding rather than complex mathematics, and drawing on real-world datasets, this book provides a step-by-step guide to comprehensive multiverse analysis. Go beyond traditional, single-path methods and discover how multiverse analysis can lead to more transparent, illuminating, and persuasive empirical contributions to science.
Issues in Metrical Phonology
Authors: Łukaszewicz Beata , Mołczanow Janina
Published: February 2025

Metrical systems differ in patterns of stress assignment, the domains over which those patterns are built, and acoustic manifestations of stress. It has been widely debated in the phonological/phonetic literature how stress should be represented, what mechanisms govern its assignment, and whether the phonetic underpinnings of primary/secondary stress exist independently of other prominence effects (e.g. boundary strengthening, pitch accents). This Element addresses these fundamental issues on the basis of an in-depth study of a hybrid (lexical-grammatical) metrical system of Ukrainian. It synthesizes previous results with new findings, focusing on the phonetic as well as formal description of the Ukrainian system. The lexical-grammatical stress interactions in Ukrainian pose a challenge for current metrical theories, shed light on the relation between the lexical and grammatical stress domains, and the relationship between categorical and gradient aspects of the metrical system. This title is also available as Open Access on Cambridge Core.
Women and Colonial Law
Authors: Nair Janaki
Published: February 2025

This book introduces students of law and history to key colonial moments that have shaped women's legal status up to the present day. It introduces students and general readers to the critical events and legal decisions that determined the place of women under law. It also introduces readers to terms that are critical to understanding women's legal status in India today. In addition to bringing together the latest developments in Indian historical research with advances in feminist legal studies, it tracks the shifts and changes that have occurred, especially over the last 30 years, to feminist standpoints on women and law. Using examples and cases from different regions of India, it also weaves together a complex and nuanced account of colonial social history more generally. This title is available as Open Access on Cambridge Core.
Natural language processing applications for low-resource languages
Authors: Pakray Partha , Gelbukh Alexander , Bandyopadhyay Sivaji
Published: February 2025

Natural language processing (NLP) has significantly advanced our ability to model and interact with human language through technology. However, these advancements have disproportionately benefited high-resource languages with abundant data for training complex models. Low-resource languages, often spoken by smaller or marginalized communities, need help realizing the full potential of NLP applications. The primary challenges in developing NLP applications for low-resource languages stem from the need for large, well-annotated datasets, standardized tools, and linguistic resources. This scarcity of resources hinders the performance of data-driven approaches that have excelled in high-resource settings. Further, low-resource languages frequently exhibit complex grammatical structures, diverse vocabularies, and unique social contexts, which pose additional challenges for standard NLP techniques. Innovative strategies are emerging to address these challenges. Researchers are actively collecting and curating datasets, even utilizing community engagement platforms to expand data resources. Transfer learning, where models pre-trained on high-resource languages are adapted to low-resource settings, has shown significant promise. Multilingual models like Multilingual Bidirectional Encoder Representations from Transformers (mBERT) and Cross Lingual Models (XLM-R), trained on vast quantities of multilingual data, offer a powerful avenue for cross-lingual knowledge transfer. Additionally, researchers are exploring integrating multimodal approaches, combining textual data with images, audio, or video, to enhance NLP performance in low-resource language scenarios. This survey covers applications like part-of-speech tagging, morphological analysis, sentiment analysis, hate speech detection, dependency parsing, language identification, discourse annotation guidelines, question answering, machine translation, information retrieval, and predictive authoring for augmentative and alternative communication systems. The review also highlights machine learning approaches, deep learning approaches, Transformers, and cross-lingual transfer learning as practical techniques. Developing practical NLP applications for low-resource languages is crucial for preserving linguistic diversity, fostering inclusion within the digital world, and expanding our understanding of human language. While challenges remain, the strategies outlined in this survey demonstrate the ongoing progress and highlight the potential for NLP to empower communities that speak low-resource languages and contribute to a more equitable landscape within language technology.
Nutrient intake variability and number of days needed to estimate usual intake in children and adolescents with autism spectrum disorder
Authors: Silva Eduarda , Hoffmann Laura , Castro Kamila , Verly Junior Eliseu , Valle Sandra , Vaz Juliana
Published: February 2025

Children and adolescents diagnosed with autism spectrum disorder (ASD) present feeding problems that may influence food acceptance and refusal. However, data regarding dietary intake variability in this population are either not available in the literature or not well-known. This cross-sectional study aimed to identify the within-person and between-person variability, and the number of days needed for a 24-hour recall (24HR) to estimate the usual intake of children and adolescents with ASD. Data were collected from 284 patients assisted at a public neuropediatric health service in the city of Pelotas, Southern Brazil. Food consumption was assessed using three non-consecutive 24HR. Within-person (S2w) and between-person (S²b) variances, the variance ratio (VR), and the distribution of energy, macronutrients, and micronutrients were obtained using the Multiple Source Method® (version 1.0.1). The number of days of 24HR needed was calculated for correlation coefficients of 0.7, 0.8, and 0.9. For most nutrients, S²w was greater than S²b, resulting in RV>1, except for age-group analyses where children up to 5 years old showed VR<1. Two to three days of 24HR were estimated for most nutrients, considering a correlation coefficient of 0.8. Differences were observed according to sex and age group, with adolescents requiring more days of 24HR. These findings indicate the need to assess dietary variability among individuals with ASD according to the characteristics of this investigated population.
Connan Mockasin as Mr Bostyn: the popular music artist in disguise, the performance of the popular music artist.
Authors: Vannieuwenhuyze Tessa
Published: February 2025

The cross-pollination between popular music and performance that Philip Auslander has coined as ‘musical persona’ is a concept that is continuously renegotiated against ongoing developments on the intersection of music, performance, technology and new media. Zooming in on the entanglement of character, persona and real person in contemporary popular music culture, this article examines how the identity performance of indie musician Connan Mockasin stages the interlacement of fictional characters and other forms of self-presentation. The fictional music teacher character Mr Bostyn that Mockasin has introduced with the Jassbusters album exists in an intriguing interplay with his broader eccentric identity performance, as demonstrated by the artist's self-presentation with an album collaboration with his father, It's Just Wind. Through the prism of the fictional band frame and music documentary practices I argue that Mockasin's self-presentation across various media formats turns the interplay between theatrical play and performative display into a fundamental aspect of his persona.
The Evolution of Law Librarianship and the Role of AI
Authors: Mills Melissa
Published: February 2025

The transformative journey of law librarianship has been marked by significant milestones, from the transition from hard copy to online access, to the current development and implementation of artificial intelligence (AI). This article is based on a presentation at the BIALL Conference in June 2024 by Melissa Mills, Knowledge Manager at William Roberts Lawyers, and explores this evolution, focusing on her experiences and insights gained over the years, particularly in the Australian context.
Micro‐CT Characterization of the Chang'e‐5 Lunar Regolith Samples
Authors: Wu Huanyu , Zou Yuan , Zhang Chi , Yang Wei , Wu Bo , Yung Kai‐Leung , Zhao Qi
Published: February 2025

Chang'e‐5 (CE‐5) lunar regolith samples were scanned using X‐ray micro‐computed tomography (micro‐CT), and over 0.7 million particles were extracted from the images through machine learning‐based segmentation. This is the largest three‐dimensional (3D) image data set on lunar regolith particles to date, offering a unique opportunity to study the key characteristics of the lunar regolith. The image intensity was correlated with mineral density, allowing for the assessment of the bulk density (1.58 g/cm3), true density (3.17 g/cm3), and mineralogy of the lunar regolith. Glass and plagioclase contributed 45.6 wt.% of the samples, while pyroxene and olivine made up 49.7 wt.%, and ilmenite accounted for 4.7 wt.%. The median grain size of CE‐5 was 57.5 μm, smaller than the Apollo 11, 16 and Luna 16, 20 and 24 samples. Spherical harmonic (SH) analysis and aspect ratio (AR) measurement revealed that the CE‐5 lunar regolith particles have more complex shapes than two common terrestrial soils and exhibit less spherical shapes than Apollo 11, 16 and Luna 16, 20 and 24 samples. We recommend using size and shape characteristics cautiously when inferring the lunar regolith maturity because the intrinsic crystal size of the protolith and complex lunar surface weathering can cause significant size and shape variations. Additionally, characterizing particle shapes requires a large sample size (>1,000) to prevent skewed results from outliers. Our non‐destructive examination method offers a novel and appealing approach for analyzing critical physical, mineralogical, and morphological properties of million‐scale extraterrestrial soil particles, paving the way for future deep space explorations.
Role of pancreatic lipase inhibition in obesity treatment: mechanisms and challenges towards current insights and future directions
Authors: Subramaniyan Vetriselvan , Hanim Yusoff Umul
Published: February 2025

The worldwide health emergency of obesity is closely connected to how dietary fats are metabolized, whereas the process is significantly influenced by pancreatic lipase (PL), an enzyme critical for lipid hydrolysis into fatty acids. This narrative review employs a methodological approach utilizing literature searches of PubMed data up to March 2024. The search term criteria encompasses keywords related to the role, mechanism, challenges, and current and future treatments of pancreatic lipase in obesity with an overall references is 106. This paper offers a comprehensive explanation of the role of PL, underlining its significance in the digestive process and lipid imbalances that contribute to obesity and by extension, its impact on obesity development and progression. Additionally, it delves into the dual functionality of the pancreas, emphasizing its impact on metabolism and energy utilization which, when dysregulated, promotes obesity. A focal point of this review is the investigation into the efficacy, challenges, and adverse effects of current pancreatic lipase inhibitors, with orlistat being highlighted as a primary current drug delivery. By discussing advanced obesity treatments, including the exploration of novel anti-obesity medications that target specific biological pathways, this review underscores the complexity of obesity treatment and the necessity for a multifaceted approach. In conclusion, this paper emphasizing the importance of understanding the role of enzymes like pancreatic lipase mechanistic and adopting a multidisciplinary approach to treatment and side effects of current obesity drugs and explore new emerging therapeutic strategies for more effective obesity management.
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Prolactin levels and chronic kidney disease and the subsequent risk of cardiovascular events: A long term population based cohort study
Authors: Rojhani Ehsan , Rahmati Maryam , Firouzi Faegheh , Ziaeefar Pardis , Soudmand Saber Amanollahi , Azizi Fereidoun , Tehrani Fahimeh Ramezani , Behboudi-Gandevani Samira
Published: February 2025

Both the clearance and secretion of prolactin are disrupted in chronic kidney disease (CKD). Evidence indicates that prolactin may play a role in cardiovascular (CV) disturbances. Considering the increased cardiovascular risk associated with CKD, this study investigates the relationship between prolactin levels, CKD, and the risk of CV events in both women and men, with an average follow-up period of 20 years. The study included 2,005 participants from the Tehran Lipid and Glucose Study (TLGS) who met the inclusion criteria. They were reassessed approximately every three years for a median follow-up of 19.0 years (Interquartile range (IQR):16.4–20.2), during which occurrences of CKD and CV events were recorded. A pooled logistic regression model examined the influence of Prolactin on CV events and its interaction with CKD. During follow-up, we identified 156 incident cases of CV events among men and 73 among women. Median (95%CI) PRL levels were 7.4 (5.5–10.5) ng/mL for men and 15.2 (10.3–23) ng/mL for women. The results of analyses showed that a history of CKD was associated with significantly higher odds of CV events for both men 4.2 (95% CI: 2.6–6.8) and women 5.5 (95% CI: 2.6–11.5). Results remained unchanged after adjustment for confounders including age, waist circumference, smoking, education, history of diabetes and hypertension, and family history of CV events. Interaction analyses revealed no statistically significant interaction between CKD and PRL on the odds of CV events in unadjusted and adjusted models. This consistent pattern was observed regardless of gender. Results of population-based data with over a median follow-up period of 20 years showed that CKD independently increases the risk of CV events in both men and women. However, our findings suggest that this elevated risk may not be substantially influenced by prolactin levels. Further investigation may be warranted to confirm these findings.
3D quantification of metal-induced geometric distortions in MRI
Authors: Li Hao , Özen Ali C. , Juerchott Alexander , Breckwoldt Michael , Jesser Jessica , Vollherbst Dominik F. , Schwarz Daniel , Bendszus Martin , Heiland Sabine , Hilgenfeld Tim
Published: February 2025

The increasing number of patients with metal implants raises concerns about metal-induced geometric distortions (MD) in MR-guided treatments. This study proposes a method for three-dimensional quantification of MD and evaluates its accuracy and reliability. A 3D lattice phantom was designed and measured with two sequences (VIBE and SPACE) and two implants (crown-supported-dental-implant and stainless-steel-bracket). Automated detection of displacement of 9360 crossing points caused by MD was performed. Distortion-quantification accuracy was improved by correcting for noise-induced error (NE), related to different signal-to-noise ratios (SNR), and implant-related signal loss and pile-up artifact volumes (SLPUA). The method’s accuracy was validated against computed tomography. Results showed high reliability, with an excellent intraclass correlation coefficient (≥ 0.99) and low mean residual errors in all directions (2.6%/1.6%/1.8% of voxel size in X/Y/Z direction). SNR/SLPUA volumes were significant confounders (p-value ≤ 0.001) when comparing different sequences/implants, but corrections significantly reduced their impacts (p-value ≤ 0.001). This method enables accurate 3D MD quantification and fair comparison across different sequences/implants. By optimizing MRI protocols for MD minimization and defining implant-specific MD profiles for patient data correction, it may help improve spatial accuracy in MRI-guided treatments in the future.
AgRP neurons shape the sperm small RNA payload
Authors: Tahiri Iasim , Llana Sergio R. , Díaz-Castro Francisco , Claret Marc , Obri Arnaud
Published: February 2025

Paternal dietary patterns and obesity can affect offspring through epigenetic signals in sperm RNA. By activating hypothalamic Agouti-related peptide (AgRP) neurons in mice to simulate obesity’s effects, we observed changes in the small noncoding RNA payload of sperm. These alterations, particularly in transfer RNA-derived small RNAs (tsRNAs), are similar to those induced by short-term high-fat diets, suggesting a common upstream regulatory mechanism involving AgRP neurons that affects metabolic epigenetic inheritance.
Use of HSALR female mice as a model for the study of myotonic dystrophy type I
Authors: Carrascosa-Sàez Marc , Colom-Rodrigo Anna , González-Martínez Irene , Pérez-Gómez Raquel , García-Rey Andrea , Piqueras-Losilla Diego , Ballestar Ana , Llamusí Beatriz , Cerro-Herreros Estefanía , Artero Ruben
Published: February 2025

HSALR mice are the most broadly used animal model for studying myotonic dystrophy type I (DM1). However, so far, HSALR preclinical studies have often excluded female mice or failed to document the biological sex of the animals. This leaves an unwanted knowledge gap concerning the differential development of DM1 in males and females, particularly considering that the disease has a different clinical presentation in men and women. Here we compared typical functional measurements, histological features, molecular phenotypes and biochemical plasma profiles in the muscles of male and female HSALR mice in search of any significant between-sex differences that could justify this exclusion of female mice in HSALR studies and, critically, in candidate therapy assays performed with this model. We found no fundamental differences between HSALR males and females during disease development. Both sexes presented comparable functional and tissue phenotypes, with similar molecular muscle profiles. The only sex differences and significant interactions observed were in plasma biochemical parameters, which are also intrinsically variable in patients with DM1. In addition, we tested the influence of age on these measurements. We therefore suggest including female HSALR mice in regular DM1 studies, and recommend documenting the sex of animals, especially in studies focusing on metabolic alterations. This will allow researchers to detect and report any potential differences between male and female HSALR mice, especially regarding the efficacy of experimental treatments that could be relevant to patients with DM1.
A combination of measures limits demand for critical materials in Sweden’s electric car transition
Authors: Morfeldt Johannes , Johansson Daniel J. A. , Davidsson Kurland Simon
Published: February 2025

Electrification of passenger cars will result in an increased demand for critical raw materials. Here we estimate the quantities of nickel, manganese, cobalt, lithium, and graphite that could be required for a transition to electric cars in Sweden and how different measures can limit material demand. We find notable reduction potentials for shorter battery range—enabled by improved charging infrastructure, increased vehicle energy efficiency, and reduced travel demand compared to a reference scenario. The reduction potentials for downsizing and more lightweight cars, and car sharing are more modest. The combined impact of these measures would be 50–75% reduction in cumulative demand and 72–87% reduction in in-use stock in 2050, depending on the material and battery chemistry pathway. Generally, the reduction potentials are larger than the potential contributions from recycling, suggesting that these complementary measures may be more effective in reducing material demand.
Sediment resuspension in muddy sediments enhances pyrite oxidation and carbon dioxide emissions in Kiel Bight
Authors: Kalapurakkal Habeeb Thanveer , Dale Andrew W. , Schmidt Mark , Taubner Heidi , Scholz Florian , Spiegel Timo , Fuhr Michael , Wallmann Klaus
Published: February 2025

Sediment resuspension of blue carbon ecosystems (e.g., seagrass beds) and muddy sediments exposes buried particulate organic carbon to oxygenated waters and remineralization, potentially enhancing carbon dioxide fluxes. However, the kinetics of carbon degradation under oxic and anoxic conditions are poorly constrained. We report the results of incubation experiments with sediments from Kiel Bight to simulate sediment resuspension events induced by natural and anthropogenic resuspension in this area. A numerical model determined that oxic carbon remineralization rates were up to two-fold higher than those under anoxic conditions. A coupled sediment-water column model demonstrated that pyrite oxidation, rather than carbon oxidation, has the potential to induce large carbon dioxide emissions to the atmosphere following anthropogenic sediment disturbance by trawling. Upscaling to muddy areas of Kiel Bight suggests an annual emission of up to ~14 k tonnes of carbon dioxide per year. Pyrite oxidation may contribute to a weakening of the carbon shelf pump and a reduction of anthropogenic carbon dioxide uptake.
CITRINO: phase 1 dose escalation study of anti-LAG-3 antibody encelimab alone or in combination with anti-PD-1 dostarlimab in patients with advanced/metastatic solid tumours
Authors: Hecht J. Randolph , Michot Jean-Marie , Bajor David , Patnaik Amita , Chung Ki Y. , Wang Judy , Falchook Gerald , Cleary James M. , Kim Richard , Krishnamurthy Anuradha , Marathe Omkar , Youssoufian Hagop , Ellis Catherine , Waszak Angela , Ghosh Srimoyee , Zhang Hailei , Yablonski Kaitlin , Shah Shruti D. , Diaz-Padilla Ivan , Ulahannan Susanna
Published: February 2025

Background

Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.

Methods

Part 1 (P1) involved dose escalation (20–720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.

Results

Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.

Conclusions

Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.

Clinical trial registration

NCT03250832.
Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance
Authors: Ingham James , Ruan Jia-Ling , Coelho Matthew A.
Published: February 2025

Most cancer-related deaths result from drug-resistant disease(1,2). However, cancer drug resistance is not a primary focus in drug development. Effectively mitigating and treating drug-resistant cancer will require advancements in multiple fields, including early detection, drug discovery, and our fundamental understanding of cancer biology. Therefore, successfully tackling drug resistance requires an increasingly multidisciplinary approach. A recent workshop on cancer drug resistance, jointly organised by Cancer Research UK, the Rosetrees Trust, and the UKRI-funded Physics of Life Network, brought together experts in cell biology, physical sciences, computational biology, drug discovery, and clinicians to focus on these key challenges and devise interdisciplinary approaches to address them. In this perspective, we review the outcomes of the workshop and highlight unanswered research questions. We outline the emerging hallmarks of drug resistance and discuss lessons from the COVID-19 pandemic and antimicrobial resistance that could help accelerate information sharing and timely adoption of research discoveries into the clinic. We envisage that initiatives that drive greater interdisciplinarity will yield rich dividends in developing new ways to better detect, monitor, and treat drug resistance, thereby improving treatment outcomes for cancer patients.