bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal exposure to endocrine disrupting chemicals and the association with behavioural difficulties in 7-year-old children in the SELMA study
Authors: Stratmann Marlene , Özel Fatih , Marinopoulou Maria , Lindh Christian , Kiviranta Hannu , Gennings Chris , Bornehag Carl-Gustaf 
Published: December 2024

Abstract
Background
Endocrine disrupting chemicals (EDCs) can cross the placenta and thereby expose the fetus, which may lead to developmental consequences. It is still unclear which chemicals are of concern regarding neurodevelopment and specifically behaviour, when being exposed to a mixture.

Objective
The objective is to determine associations between prenatal exposure to EDCs and behavioural difficulties. Furthermore, we investigated sex-specific associations and determined chemicals of concern in significant regressions.

Methods
Associations between prenatal exposure to EDCs (both as single compounds and their mixtures) and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ) were estimated in 607 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study. Levels for chemical compounds were measured in either urine or serum (median of 10 weeks of gestation). Associations were estimated for the total SDQ score (quasipoisson regression) and a 90th percentile cut-off (logistic regression). Exposure for EDC mixtures (phenols, phthalates, PFAS and persistent chlorinated) was studied using weighted quantile sum (WQS) regression with deciles and with and without repeated holdout validation techniques. The models were adjusted for selected covariates.

Results
The odds for behavioural difficulties increased in girls with higher chemical exposures (OR 1.77, 95% CI 1.67, 1.87) using the full sample and borderline for the validation set (OR 1.31, 95% CI 0.93, 1.85) with 94/100 positive betas in the 100 repeated holdout validations. Chemicals of concern for girls are mostly short-lived chemicals and more specifically plasticizers. No pattern of significant associations was detected for boys.

Significance
There is an indication of increased behavioural difficulties for girls in the SELMA population with higher exposure to mixtures of EDCs. Using the repeated holdout validation techniques, the inference is more stable, reproducible and generalisable. Prenatal exposure to mixtures of environmental chemicals should be considered when assessing the safety of chemicals.

Impact
Growing evidence points towards a “mixture effect” where different environmental chemicals might act jointly where individual compounds may be below a level of concern, but the combination may have an effect on human health. We are constantly exposed to a complicated mixture pattern that is individual for every person as this mixture depends on personal choices of lifestyle, diet and housing to name a few. Our study suggests that prenatal exposure to EDCs might adversely affect the behaviour of children and especially girls. Hence, risk assessment needs to improve and sex-specific mechanisms should be included in assessments.
The accuracy of fluorine 18-labelled prostate-specific membrane antigen PET/CT and MRI for diagnosis of prostate cancer in PSA grey zone
Authors: Luo Liang , Wang Ruiyan , Bai Lu , Shang Jin , Wang Xinyi , Chang Ruxi , Dong Weixuan , Li Yang , Li Yan , Liang Hua , Xie Hongjun , Duan Xiaoyi 
Published: December 2024

Abstract

Background
The diagnostic utility of prostate biopsy is limited for prostate cancer (PCa) in the prostate-specific antigen (PSA) grey zone. This study aims to evaluate the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for PSA grey zone PCa and clinically significant PCa (csPCa).

Methods
A total of 82 patients with PSA levels ranging from 4 to 10 ng/mL who underwent 18F-PSMA-1007 PET/CT, mpMRI, and prostate biopsy were prospectively enrolled. For 18F-PSMA-1007 PET/CT and mpMRI in detecting PCa and csPCa, sensitivity, specificity, and area under the curve (AUC) were assessed using biopsy histology as the standard.

Results

18F-PSMA-1007 PET/CT demonstrated better diagnostic performance for PCa than mpMRI (AUC 0.81 vs. 0.63, P = 0.02). 11.0% of patients with PI-RADS 3-5 had no PCa on biopsy, of whom 77.8% were correctly differentiated by 18F-PSMA-1007 PET/CT. Combined 18F-PSMA-1007 PET/CT + mpMRI improved sensitivity (92.5% vs. 73.6%) and negative predictive value (NPV, 78.9% vs. 53.3%) compared with mpMRI alone.

Conclusions

18F-PSMA-1007 PET/CT outperformed mpMRI for detecting PCa in the grey zone level of PSA. 18F-PSMA-1007 PET/CT in combination with mpMRI has additional improvement in sensitivity and NPV for csPCa detection.

Clinical Trial Registration: NCT05958004, 2024-07.
PP2C phosphatases—terminators of suicidal thoughts
Authors: Lagorgette Lisa , Bogdanova Daria A. , Belotserkovskaya Ekaterina V. , Garrido Carmen , Demidov Oleg N. 
Published: December 2024

AbstractCell death and related signaling pathways are essential during development and in various physiological and pathological conditions. Post-translational modifications such as ubiquitination and phosphorylation play an important role in these signaling pathways. The involvement of kinases - enzymes that catalyze protein phosphorylation - in cell death signaling has been extensively studied. On the other hand, not many studies have been devoted to analyzing the role in cell death of phosphatases, enzymes involved in the removal of phosphorylated residues added to proteins by kinases. Obviously, the two opposite reactions, phosphorylation and dephosphorylation, are equally important in the regulation of protein functions and subsequently in the execution of the cell death program. Here, we have summarized recent work on the involvement of serine-threonine PP2C phosphatases in cell death pathways, senescence and autophagy, focusing in particular on the most studied phosphatase PPM1D (PP2Cδ) as an example of the regulatory role of PP2Cs in cell death. The review should help to draw attention to the importance of PP2C family phosphatases in cell death checkpoints and to discover new targets for drug development.
A family of NADPH/NADP+ biosensors reveals in vivo dynamics of central redox metabolism across eukaryotes
Authors: Scherschel Marie , Niemeier Jan-Ole , Jacobs Lianne J. H. C. , Hoffmann Markus D. A. , Diederich Anika , Bell Christopher , Höhne Pascal , Raetz Sonja , Kroll Johanna B. , Steinbeck Janina , Lichtenauer Sophie , Multhoff Jan , Zimmermann Jannik , Sadhanasatish Tanmay , Rothemann R. Alexander , Grashoff Carsten , Messens Joris , Ampofo Emmanuel , Laschke Matthias W. , Riemer Jan , Roma Leticia Prates , Schwarzländer Markus , Morgan Bruce 
Published: December 2024

AbstractThe NADPH/NADP+ redox couple is central to metabolism and redox signalling. NADP redox state is differentially regulated by distinct enzymatic machineries at the subcellular compartment level. Nonetheless, a detailed understanding of subcellular NADP redox dynamics is limited by the availability of appropriate tools. Here, we introduce NAPstars, a family of genetically encoded, fluorescent protein-based NADP redox state biosensors. NAPstars offer real-time, specific measurements, across a broad-range of NADP redox states, with subcellular resolution. NAPstar measurements in yeast, plants, and mammalian cell models, reveal a conserved robustness of cytosolic NADP redox homoeostasis. NAPstars uncover cell cycle-linked NADP redox oscillations in yeast and illumination- and hypoxia-dependent NADP redox changes in plant leaves. By applying NAPstars in combination with selective impairment of the glutathione and thioredoxin antioxidative pathways under acute oxidative challenge, we find an unexpected and conserved role for the glutathione system as the primary mediator of antioxidative electron flux.
Age- and sex-related variations in extracellular vesicle profiling for the assessment of cardiovascular risk: the EVaging index
Authors: Burrello Jacopo , Goi Jessica , Burrello Alessio , Vacchi Elena , Rendon-Angel Azucena , Lazzarini Edoardo , Bianco Giovanni , Limongelli Vittorio , Vassalli Giuseppe , Cereda Carlo W. , Monticone Silvia , Mulatero Paolo , Bussolati Benedetta , Alimonti Andrea , Camici Giovanni G. , Melli Giorgia , Osto Elena , Pedrazzini Giovanni , Lucio Barile 
Published: December 2024

AbstractExtracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation (“inflammaging”) and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups. The EVaging index was associated with age in healthy individuals and distinguished CV risk profiles in patients, correlating with CV outcomes and likelihood of fatal CV events according to the European Society of Cardiology (ESC) SCORE, and reflecting age-associated comorbidities. While changes in disease-related EV fingerprint adds complexity in CV patients, EV profiling may help assess biological aging and CV risk, emphasizing EVs’ roles in inflammaging.
Chemical ordering and magnetism in face-centered cubic CrCoNi alloy
Authors: Ghosh Sheuly , Ueltzen Katharina , George Janine , Neugebauer Jörg , Körmann Fritz 
Published: December 2024

AbstractThe impact of magnetism on chemical ordering in face-centered cubic CrCoNi medium entropy alloy is studied by a combination of ab initio simulations, machine learning potentials, and Monte Carlo simulations. Large magnetic energies are revealed for some mixed L12/L10 type ordered configurations, which are rooted in strong nearest-neighbor magnetic exchange interactions and chemical bonding among the constituent elements. There is a delicate interplay between magnetism and stability of MoPt2 and L12/L10 type of order, which may explain opposing experimental and theoretical findings.
Psychomotor slowing in schizophrenia is associated with aberrant postural control
Authors: Nuoffer Melanie G. , Schindel Anika , Lefebvre Stephanie , Wüthrich Florian , Nadesalingam Niluja , Kyrou Alexandra , Kerkeni Hassen , Kalla Roger , Bernard Jessica , Walther Sebastian 
Published: December 2024

AbstractMotor abnormalities, including psychomotor slowing, are prevalent in a large proportion of individuals with schizophrenia. While postural control deficits have been observed in this population, the impact of motor abnormalities on postural stability remains unclear. This study aimed to objectively evaluate postural stability in patients with and without psychomotor slowing and healthy controls. Seventy-three schizophrenia patients with psychomotor slowing (PS; Salpêtrière Retardation Rating Scale (SRRS) ≥ 15), 25 schizophrenia patients without psychomotor slowing (non-PS; SRRS < 15), and 27 healthy controls (HC) performed four conditions on the Kistler force plate: eyes open (EO), eyes closed (EC), head reclined with eyes open (EOHR), and head reclined with eyes closed (ECHR). Larger sway areas and higher Root Mean Square (RMS) values indicate lower postural stability, while a lower Complexity Index (CI) reflects reduced adaptability, flexibility, and dynamic functioning of postural control. PS exhibited larger sway areas and higher RMS compared to the other groups. Both PS and non-PS showed reduced complexity in postural control compared to healthy controls, without differences between the two patient groups. Reduced postural stability and complexity were associated with greater expert-rated motor abnormalities, as well as more severe negative symptoms. Additionally, lower complexity was linked to reduced physical activity levels. These findings suggest that psychomotor slowing is associated with lower postural stability, potentially reflecting impaired cerebellar function. Furthermore, the loss of complexity in postural control highlights reduced flexibility, adaptability, and efficiency in the postural control network of individuals with schizophrenia.
Replicating RNA vaccine confers durable immunity against Crimean Congo hemorrhagic fever virus challenge in mice
Authors: Leventhal Shanna S. , Shaia Carl , Rao Deepashri , Lewis Matthew , Meade-White Kimberly , Erasmus Jesse H. , Feldmann Heinz , Hawman David W. 
Published: December 2024

AbstractSpread by Hyalomma genus ticks, Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic disease endemic throughout Southern and Eastern Europe, Asia, and Africa. To date, there are no widely approved vaccines for CCHFV and treatment for disease is largely supportive. Due to this lack of intervention, the WHO lists CCHFV as a high-priority pathogen. Recently, we described a highly efficacious self-replicating RNA vaccine which is protective against CCHFV disease in mice and non-human primates. This vaccine induces high titers of non-neutralizing anti-nucleoprotein (NP) antibodies and a robust T-cell response against the viral glycoprotein. Here, we assess the durability of this vaccine in mice by monitoring the immunogenicity and efficacy of this vaccine up to 1 year post vaccination. We found that while glycoprotein-specific T-cell responses and anti-NP antibody titers waned over time, mice remained protected against lethal CCHFV challenge for at least 1 year post vaccination.
A reinforced lunar dynamo recorded by Chang’e-6 farside basalt
Authors: Cai Shuhui , Qi Kaixian , Yang Saihong , Fang Jie , Shi Pingyuan , Shen Zhongshan , Zhang Min , Qin Huafeng , Zhang Chi , Li Xiaoguang , Chen Fangfang , Chen Yi , Li Jinhua , He Huaiyu , Deng Chenglong , Li Chunlai , Pan Yongxin , Zhu Rixiang 
Published: December 2024

Abstract
The evolution of the lunar dynamo is essential for deciphering the deep interior structure, thermal history and surface environment of the Moon1–4. Previous palaeomagnetic investigations on samples returned from the nearside of the Moon have established the general variation of the lunar magnetic field5–7. However, limited spatial and temporal palaeomagnetic constraints leave the evolution of the lunar dynamo ambiguous. The Chang’e-6 mission returned the first farside basalts dated at about 2.8 billion years ago (Ga) (refs. 8,9), offering an opportunity to investigate a critical spatiotemporal gap in the evolution of the global lunar dynamo. Here we report palaeointensities (around 5–21 μT) recovered from the Chang’e-6 basalts, providing the first constraint on the magnetic field from the lunar farside and a critical anchor within the large gap between 3 Ga and 2 Ga. These results record a rebound of the field strength after its previous sharp decline of around 3.1 Ga, which attests to an active lunar dynamo at about 2.8 Ga in the mid-early stage and argues against the suggestion that the lunar dynamo may have remained in a low-energy state after 3 Ga until its demise. The results indicate that the lunar dynamo was probably driven by either a basal magma ocean or a precession, supplemented by other mechanisms such as core crystallization.
First-principles study of the magneto-Raman effect in van der Waals layered magnets
Authors: Kong Xiangru , Ganesh Panchapakesan , Liang Liangbo 
Published: December 2024

AbstractMagneto-Raman spectroscopy has been used to study spin-phonon coupling in two-dimensional (2D) magnets. Raman spectra of CrI3 show a strong dependence on the magnetic order within a layer and between the layers. Here we carry out the first systematic theoretical investigation of the magneto-Raman effect in 2D magnets by performing density functional theory calculations and developing a generalized polarizability model. Our first-principles simulations well reproduce experimental Raman spectra of CrI3 with different magnetic states. The model reveals how the change of spin orientation in each layer is coupled to the layer’s vibration to induce or eliminate the spin-dependent anti-symmetric off-diagonal terms in the Raman tensor for altering the selection rules. We also uncover that the correlation between phonon modes and magnetic orders is a universal phenomenon, which should exist in other phonon modes and 2D magnets. Our predictive simulations and modeling are expected to guide the research in 2D magnets.
A deep learning framework deploying segment anything to detect pan-cancer mitotic figures from haematoxylin and eosin-stained slides
Authors: Shen Zhuoyan , Simard Mikaël , Brand Douglas , Andrei Vanghelita , Al-Khader Ali , Oumlil Fatine , Trevers Katherine , Butters Thomas , Haefliger Simon , Kara Eleanna , Amary Fernanda , Tirabosco Roberto , Cool Paul , Royle Gary , Hawkins Maria A. , Flanagan Adrienne M. , Collins-Fekete Charles-Antoine 
Published: December 2024

AbstractMitotic activity is an important feature for grading several cancer types. However, counting mitotic figures (cells in division) is a time-consuming and laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment. This study presents an artificial intelligence-based approach to detect mitotic figures in digitised whole-slide images stained with haematoxylin and eosin. Advances in this area are hampered by the small size and variety of datasets available. To address this, we create the largest dataset of mitotic figures (N = 74,620), combining an in-house dataset of soft tissue tumours with five open-source datasets. We then employ a two-stage framework, named the Optimised Mitoses Generator Network (OMG-Net), to identify mitotic figures. This framework first deploys the Segment Anything Model to automatically outline cells, followed by an adapted ResNet18 that distinguishes mitotic figures. OMG-Net achieves an F1 score of 0.84 in detecting pan-cancer mitotic figures, including human breast carcinoma, neuroendocrine tumours, and melanoma. It outperforms previous state-of-the-art models in hold-out test sets. To summarise, our study introduces a generalisable data creation and curation pipeline and a high-performance detection model, which can largely contribute to the field of computer-aided mitotic figure detection.
Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide
Authors: Ren Jiajun , Mathew Anugraha , Rodríguez-García María , Kohler Tobias , Blacque Olivier , Linden Anthony , Eberl Leo , Sieber Simon , Gademann Karl 
Published: December 2024

AbstractChirality plays a critical role in the biochemistry of life and often only one enantiomeric series is observed (homochirality). Only a few natural products have been obtained as racemates, e.g. the signalling molecule valdiazen produced by Burkholderia cenocepacia H111. In this study, we investigated the ham biosynthetic gene cluster and discovered that both the enantiomerically pure (R)-fragin and the racemic valdiazen result from the same pathway. This stereodivergence is based on the unusual heterocyclic intermediate dihydrosydnone N-oxide, as evident from gene knockout, stable isotope feeding experiments, and mass spectrometry experiments. Both non-enzymatic racemisation via keto-enol tautomerisation and enzyme-mediated dynamic kinetic resolution were found to be crucial to this stereodivergent pathway. This novel mechanism underpins the production of configurationally and biologically distinct metabolites from a single gene cluster. Our findings highlight the intricate design of an intertwined biosynthetic pathway and provide a deeper understanding of microbial secondary metabolism related to microbial communication.
High triplet energy host material with a 1,3,5-oxadiazine core from a one-step interrupted Fischer indolization
Authors: Riley Charlotte , Cho Hwan-Hee , Brannan Alexander C. , Le Phuoc Nguyen , Linnolahti Mikko , Greenham Neil C. , Romanov Alexander S. 
Published: December 2024

AbstractEnergy-efficient and deep-blue organic light-emitting diode (OLED) with long operating stability remains a key challenge to enable a disruptive change in OLED display and lighting technology. Part of the challenge is associated with a very narrow choice of the robust host materials having over 3 eV triplet energy level to facilitate efficient deep-blue emission and deliver excellent performance in the OLED device. Here we show the molecular design of new 1,3,5-oxadiazines (NON)-host materials with high triplet energy over 3.2 eV, enabling deep-blue OLED devices with a peak external quantum efficiency of 21%. A series of NON-host materials are prepared by the condensation of substituted arylhydrazines and cyclohexylcarbaldehyde in a 2:3 ratio. This straightforward “one-pot” procedure enables the formation of indoline-containing derivatives with three fused heterocyclic rings and two stereogenic centres. All materials emit UV-fluorescence in the range of 315–338 nm while possessing highly desirable characteristics for application in deep-blue OLED devices: good thermal stability, a wide energy gap (3.9 eV), a high triplet energy level of (3.3 eV), and excellent volatility during sublimation.
Near-term carbon dioxide removal deployment can minimize disruptive pace of decarbonization and economic risks towards United States’ net-zero goal
Authors: Adun Humphrey , Ampah Jeffrey Dankwa , Bamisile Olusola , Hu Yihua , Staffell Iain , Gilani Haris R. 
Published: December 2024

AbstractDeep decarbonization is essential for achieving the Paris Agreement goals, and carbon dioxide removal is required to address residual emissions and achieve net-zero targets. However, the implications of delaying the deployment of removal technologies remain unclear. We quantify how different carbon removal methods and their deployment timing affect achieving net zero emissions by 2050 in the United States. Our findings show that postponing novel technologies until mid-century forces accelerated decarbonization of energy-intensive sectors, reducing residual emissions by at least 12% compared with near-term deployment of carbon dioxide removal. This delay increases transition costs, requiring carbon prices 59–79% higher than with near-term deployment. It also heightens the risk of premature fossil fuel retirement in the electricity sector, leading to 128–220 billion USD losses compared to gradual scale up starting now. A balanced, near-term co-deployment of novel removal methods mitigates risks associated with relying on a single approach and addresses sustainability and scalability concerns.
Regional cooling potential from expansion of perennial grasses in Europe
Authors: Zhang Xia , Huang Bo , Rinke Dias de Souza Nariê , Hu Xiangping , Cherubini Francesco 
Published: December 2024

AbstractPerennial grasses are an option to mitigate global warming, increase energy security, and alleviate environmental pressures within agricultural landscapes. Their cultivation alters near-surface temperature in ways that are still largely unclear. Here, a regional climate model with an enhanced representation of perennial grasses shows that converting today’s cropland areas in Europe induces annual mean temperature reductions in summer and autumn (up to –1 °C), which are primarily driven by a later harvest of perennial grasses relative to annual crops. Cultivation of perennial grasses where they deliver stronger biogeophysical cooling can achieve a similar annual mean temperature reduction on half of the land. This cooling can counteract up to 50% of the projected future warming and it is three times larger than what is achieved via carbon emission reductions. A sustainable deployment of perennial grasses has the potential to link global mitigation objectives with co-benefits for the local climate and environment.