bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opportunistic Quantitative Computed Tomography Assessing Bone Mineral Density in Patients With Laparoscopic Roux-En-Y-Gastric Bypass Metabolic Surgery Throughout a 5-Year Observation Window
Authors: Noser Mark-Stefan , Boll Daniel T. , Lazaridis Ioannis I. , Delko Tarik , Koestler Thomas , Zingg Urs , Potthast Silke 
Published: December 2024

Background
Bariatric surgery is associated with decreasing bone mineral density (BMD).

Objective
To assess the long-term vertebral BMD, measured by opportunistic quantitative CT (QCT), and body mass index (BMI) in patients undergoing proximal laparoscopic Roux-en-Y surgery (LRYGB).

Methods
In 62 patients undergoing LRYGB, opportunistic QCT measurements were performed extracting BMD and BMI on day 1 and years 1, 3, and 5 postoperatively.
Primarily, one-way analyses of variance were performed on dependent variables BMI and BMD, with imaging interval defined as an independent factor. Student-Newman-Keuls tests performed pairwise comparisons of imaging interval permutations for BMI/BMD.
Secondarily, analyses of covariance were used on dependent variables BMI and BMD, with imaging interval as an independent factor and gender/age as well as BMD/BMI, respectively, as covariates.

Results
A total of 227 opportunistic QCT measurements in 62 patients were performed without the need of a phantom or extra software.
The BMD decreased substantially and continuously during 1-, 3-, and 5-year follow-up observations, reaching statistical significance in pairwise comparisons for 3- and 5-year follow-up visits compared to initial BMD values as well as the 5-year follow-up visit compared to the 1-year BMD values, P < 0.001. Age and BMI were significant covariates, P < 0.001.
The BMI decreased within 1 year and stayed constant until a slight increase at 5 years was observed. Statistical significance in pairwise comparisons for first-year and 3- and 5-year follow-up visits was reached compared to initial BMI values, P < 0.001. For the BMI assessment, none of the covariates reached statistical significance.

Conclusion
Opportunistic QCT is suited for the calculation and follow-up of BMD. There was a continuous decrease of BMD after LRYGB over 5 years post-surgery, whereas BMI decreased in the first year and stayed constant thereafter. Older patients with lower BMI seem particularly prone to an accelerated BMD loss.
Universal differential equations for systems biology: Current state and open problems
Authors: Philipps Maren , Schmid Nina , Hasenauer Jan 
Published: December 2024

AbstractUniversal Differential Equations (UDEs) combine mechanistic differential equations with data-driven artificial neural networks, forming a flexible framework for modelling complex biological systems. This hybrid approach leverages prior knowledge and data to uncover unknown processes and deliver accurate predictions. However, UDEs face challenges in efficient and reliable training due to stiff dynamics and noisy, sparse data common in biology, and in ensuring the interpretability of the parameters of the mechanistic model. We investigate these challenges and evaluate UDE performance on realistic biological scenarios, providing a systematic training pipeline. Our results demonstrate the versatility of UDEs in systems biology and reveal that noise and limited data significantly degrade performance, but regularisation can improve accuracy and interpretability. By addressing key challenges and offering practical solutions, this work advances UDE methodology and underscores its potential in tackling complex problems in systems biology.
The effect of age and sex hormones on female neuromuscular function across the adult lifespan
Authors: O’Bryan Steven J. , Critchlow Annabel , Fuchs Cas , Hiam Danielle , Lamon Séverine 
Published: December 2024

AbstractNeuromuscular ageing is characterized by neural and/or skeletal muscle degeneration that decreases maximal force and power. Female neuromuscular ageing occurs earlier in life compared to males, potentially due to sex hormone changes during the menopausal transition. We quantified neuromuscular function in 88 healthy females represented equally over each decade from 18-80 years of age and investigated the potential role of decreased ovarian hormone concentrations following menopause. Neuromuscular assessment included quadriceps maximal voluntary and evoked isometric torque and surface electromyography measurements, plus one-repetition maximum leg press. Voluntary and evoked torques and one-repetition maximum decreased non-linearly with age, with accelerated reductions starting during the fourth decade. An absence of changes in volitional recruitment of existing quadriceps motor units and Ia afferent facilitation of spinal motoneurons suggests that functional decline was largely mediated by impairment in intrinsic muscle function and/or neuromuscular transmission. Maximal muscle compound action potential amplitude decreased with increasing age for rectus femoris only, indicating increased vulnerability to neuromuscular degeneration compared to vastus lateralis and medialis. In postmenopausal females, some variance in data was explained by inter-individual differences in body composition and physical activity level, however, changes in total or free concentrations of oestrogen, progesterone and/or testosterone were correlated with all age-related decreases in neuromuscular variables. In conclusion, we demonstrate an accelerated onset of neuromuscular degeneration of muscular origin around menopause onset, which is associated with changes in sex hormone concentrations. Interventions aimed at mitigating declines in ovarian hormones and their subsequent effects on neuromuscular function postmenopause should be further explored.Key PointsNeuromuscular deterioration with age is associated with poor physical function and quality of life in older adults, but female-specific trajectories and mechanisms remain unclear.This study is the first to map neuromuscular function across each decade of the adult lifespan in 88 healthy females from 18 to 80 years old and to examine the potential role of hormonal changes after menopauseWe show an accelerated reduction in neuromuscular function, primarily of muscular origin, that occurs between 40 and 50 years of age, coinciding with the onset of menopause.In postmenopausal females, age-related reductions in neuromuscular function can be explained by differences in body composition, physical activity, and sex hormone concentrations.These findings help us better understand the factors that contribute to the loss of neuromuscular function with age in females, enabling the identification of potential therapeutic interventions to prolong the female health span.
Sensitivity to temozolomide of cell lines derived from brain tumours and melanomas: relationship to MGMT gene expression
Authors: Baguley Bruce C , Joseph Wayne R , Murray Pamela M , Stowell Kathryn M , Leung Euphemia Y , Marshall Elaine S 
Published: December 2024

AbstractBackgroundWe have developed a series of low-passage melanoma and glioma cell lines and are using them to study responses to antitumour drugs. Here we have assessed responses to temozolomide, a commonly used clinical drug used for the treatment of glioblastoma and melanoma. Temozolomide acts mainly by methylation of DNA guanine and lesions can be removed by the repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). Low expression of MGMT is one of the main features associated with sensitivity to temozolomide and is usually associated with CpG methylation of the MGMT promoter. We wished to determine whether temozolomide sensitivity in these lines was related to MGMT promoter methylation and MGMT mRNA synthesis. Methods: 63 melanoma and 37 glioblastoma lines were derived from developed from surgical samples, using atmosphere of 5% oxygen for development and propagation in order to minimise oxygen toxicity. Temozolomide sensitivity (IC50data) was analysed by its effect on3H-thymidine incorporation in 5-day assays. MGMT promoter methylation status was assessed by the methylation-specific polymerase chain reaction (PCR). MGMT mRNA expression was assessed using reverse transcription and PCR. Results: 40% of the melanoma lines and 24% of the glioblastoma showed some sensitivity to temozolomide. Of the 79 cell lines analysed for MGMT mRNA expression, a good correlation was found to temozolomide resistance (p < 0.0001). Of the 100 cell lines assessed for MGMT promoter status, 12 showed methylation of both promoter sequences and were all temozolomide-sensitive; 50 lines showed no MGMT promoter methylation and 90% of these were temozolomide resistant; 30 lines showed partial promoter methylation and 53% of these were temozolomide resistant. Conclusion: Temozolomide sensitivity matched MGMT mRNA expression well but only partially matched MGMT promoter methylation. Other factors, such as loss of DNA mismatch repair capacity, may contribute to resistance.
Trade-offs associated with higher winter wheat yields in low soil organic matter cropping systems under climate change
Authors: Michel Jennifer , Leemans Vincent , Weinmann Markus , Balanzategui-Guijarro Iñaki , Bin Jimmy , Biver Simon , Blum Adrien , Börger Rachel , Cao Da , Him Sok-Lay , Kirbas Gaëlle , Le Gouis Jacques , Moya-Laraño Jordi , Persyn Mayliss , Pierreux Jérome , Quenon Alice , Sanchez-Moreno Sara , Symanczik Sarah , Brande Florian Vanden , Van Der Straeten Dominique , Wagner Markus , Waibel Matthias , Xayphrarath Anna , Vanderschuren Hervé , Thonar Cécile , Delaplace Pierre 
Published: December 2024

AbstractEmpirical data is key to anticipate the impact of climate change on cropping systems and develop land management strategies that are sustainable while ensuring food security. Here, the combined effects of projected increases in temperature, atmospheric CO2-concentrations, solar irradiation and altered precipitation patterns on winter wheat cropping systems were investigated using an Ecotron. Experimental plant-soil systems were subjected to three different climatic conditions representing a gradient of ongoing climate change implementing the weather patterns of the years 2013, 2068, and 2085 respectively. The wheat plants were grown in two differentially manged agricultural soil types: one with long-term low organic matter (OM) inputs and the other one with long-term high OM inputs. In the low OM system, the risk for plant diseases and nitrate leaching was increased, but it outperformed the high OM system with higher yields and lower CO2-emissions. Developing high-yielding cropping systems leveraging the CO2-fertilisation effect without sacrificing environmental health will therefore require further refined of management practices to improve nutrient cycling and reduce greenhouse gas emissions. One possibility is adapting crop rotations and cover crops to the shorter wheat cycle observed in the future climates to replenish soil nutrients and break disease cycles. Further, in both here studied soil types the wheat plants developed natural coping mechanisms against environmental stressors, such as enhanced root growth and increased levels of proline and silicon. Unravelling the molecular mechanisms that trigger such inherent plant defences is a further interesting target for breeding future crops.Graphical abstract
ProtSpace: a tool for visualizing protein space
Authors: Senoner Tobias , Olenyi Tobias , Heinzinger Michael , Spannagl Anton , Bouras George , Rost Burkhard , Koludarov Ivan 
Published: December 2024

ABSTRACTProtein language models (pLMs) generate high-dimensional representations of proteins, so called embeddings, that capture complex information stored in the set of evolved sequences. Interpreting these embeddings remains an important challenge.ProtSpaceprovides one solution through an open-source Python package that visualizes protein embeddings interactively in 2D and 3D. The combination of embedding space with protein 3D structure view aids in discovering functional patterns readily missed by traditional sequence analysis.We present two examples to showcaseProtSpace. First, investigations of phage data sets showed distinct clusters of major functional groups and a mixed region, possibly suggesting bias in today’s protein sequences used to train pLMs. Second, the analysis of venom proteins revealed unexpected convergent evolution between scorpion and snake toxins; this challenges existing toxin family classifications and added evidence refuting theaculeatoxin family hypothesis.ProtSpaceis freely available as a pip-installable Python package (source code & documentation) with examples on GitHub (https://github.com/tsenoner/protspace) and as a web interface (https://protspace.rostlab.org). The platform enables seamless collaboration through portable JSON session files.
Joint analysis of RNA-DNA and DNA-DNA interactomes reveals their strong association
Authors: Zvezdin Dmitry S. , Tyukaev Artyom A. , Zharikova Anastasia A. , Mironov Andrey A. 
Published: December 2024

AbstractAt the moment, many non-coding RNAs that perform a variety of functions in the regulation of chromatin processes are known. An increasing number of protocols allow researchers to study RNA-DNA interactions and shed light on new aspects of the RNA-chromatin interactome. The Hi-C protocol, which enables the study of chromatin’s three-dimensional organization, has already led to numerous discoveries in the field of genome 3D organization. We conducted a comprehensive joint analysis of the RNA-DNA interactome and chromatin structure across different human and mouse cell lines. We have shown that these two phenomena are closely related in many respects, with the nature of this relationship being both tissue-specific and conserved across human and mouse.
Shifts in honeybee worker metabolism immediately post-eclosion
Authors: Verbinnen Gilles , Roald-Arbøl Mikkel , Niven Jeremy Edward , Nicholls Elizabeth 
Published: December 2024

AbstractThe metabolic rate of an organism is intrinsically linked to key traits such as reproductive output and lifespan. While the drivers of individual differences in metabolic rate are poorly understood, previous research in insects has shown that metabolic rate can change substantially in the initial hours and days post-eclosion as adults.Here we repeatedly measured the resting and active metabolic rate of individual adult honeybees (Apis mellifera) for up to 48 hours from the time of eclosion. We combined flow-through respirometry with automated behaviour tracking, permitting us to obtain ‘active’ (AMR) and true ‘resting’ metabolic rate (RMR) from freely moving animals. We compared these recordings to the more conventional approach of obtaining resting metabolic rate by restraining animals.Both active and resting metabolic rates and mass-specific metabolic rates increased significantly in the first 48-hours post-eclosion, whereas metabolic scope did not change. Mass-specific water loss was highest in active bees and changed non-linearly with time post-eclosion, increasing in the first 24 hours before decreasing again. A similar quadratic relationship with time was also observed for bees’ movement speed. Speed- and mass-specific metabolic rate and scope increased with time post-emergence, whereas speed- and mass-specific water loss did not.The metabolic rate of restrained bees was consistently significantly higher than the true RMR at all time points, likely due to the stress associated with being restrained. Therefore, we recommend future studies of insect resting metabolic rates avoid restraining organisms to restrict movement and consider employing behaviour tracking as a means to extract metabolic rate data from periods of true rest.This study provides important insights into the previously overlooked changes in metabolism exhibited by newly emerged honeybee workers. The high mortality rate beyond 48 hours, coupled with significant changes in metabolic rates, body mass, and water loss, underscores the importance of this early post-eclosion period for survival and metabolic stabilization.
Impact of force field polarization on the collective motions of proteins
Authors: Milinski Ana , Dejaegere Annick , Stote Roland H. 
Published: December 2024

ABSTRACTCorrelated motions of proteins underpin many physiological mechanisms, such as substrate binding, signal transduction, enzymatic activity and allostery. These motions arise from low frequency collective movements of biomolecules and have mostly been studied using molecular dynamics simulations. Here, we present the effects of two different empirical energy force fields used for molecular dynamics simulations on correlated motions – the non-polarizable CHARMM 36m additive force field and the polarizable Drude force field. The study was conducted on two proteins, ubiquitin - a small protein with a well-described dynamic - and the nuclear receptor protein PPARγ. The ligand binding domain of PPARγ was of particular interest since its function is to regulate transcription through ligand and coregulator protein binding. It has been previously shown that a dynamical network of correlated motions ensures the transmission of information related to ligand binding. We present the results of classical MD simulations where we analyze the results in terms of residue fluctuations, correlation maps, community network analysis and Shortest Path Method analysis. We find that the RMS fluctuations tend to be greater and that the correlated motions are less intense when using the Drude force field than when using the non-polarizable all atom additive force field. Our results provide the first quantification of the impact of using a polarizable force field in computational studies that focus on collective motions.
The Landscape of Sex- and APOE Genotype-Specific Transcriptional Changes in Alzheimer’s Disease at the Single Cell Level
Authors: Yu Gefei , Thorpe Abigail , Zeng Qi , Wang Erming , Cai Dongming , Wang Minghui , Zhang Bin 
Published: December 2024

AbstractAlzheimer’s disease (AD) is the most common form of dementia, with approximately two-thirds of AD patients are females. Basic and clinical research studies show evidence supporting sex-specific differences contributing to the complexity of AD. There is also strong evidence supporting sex-specific interaction between the primary genetic risk factor of AD,APOE4and AD-associated neurodegenerative processes. Recent studies by us and others have identified sex and/or APOE4 specific differentially expressed genes in AD based on the bulk tissue RNA-sequencing data of postmortem human brain samples in AD. However, there lacks a comprehensive investigation of the interplay between sex and APOE genotypes at the single cell level. In the current study, we systematically explore sex and APOE genotype differences in single cell transcriptomics in AD. Our work provides a comprehensive overview of sex and APOE genotype-specific transcriptomic changes across 54 high-resolution cell types in AD and highlights individual genes and brain cell types that show significant differences between sexes and APOE genotypes. This study lays the groundwork for exploring the complex molecular mechanisms of AD and will inform the development of effective sex- and APOE-stratified interventions for AD.
Abnormal eNK cells contribute to endometrial fibrosis in intrauterine adhesions patients
Authors: Zhou Zhenhua , Weng Qiao , Liu Dan , Yao Simin , Zou Xueqin , Wang Huiyan , Zhou Zihan , Zhu Hui , Zhang Xier , Chen Ling , Zhang Xiwen , Zhao Guangfeng , Hu Yali 
Published: December 2024

AbstractEndometrial natural killer cells (eNK) at the proliferative phase are one of the major lymphocytes in the endometrium, but their phenotype and function remain elucidated. Here, we demonstrated that eNK cells had three subtypes and were different from peripheral blood NK (pbNK) and decidual NK (dNK) cells. They played an important role in maintaining the homeostasis of the endometrium through preventing endometrial stromal cells (ESCs) from the differentiation into myofibroblasts physiologically. However, in the fibrotic endometria of patients with intrauterine adhesions (IUA), eNK cells were significantly decreased and highly negatively correlated with an increase in myofibroblasts. In vitro experiments showed that eNK cells could inhibit the differentiation of ESCs into myofibroblasts and promote the dedifferentiation of myofibroblasts, in which the main effector molecules from eNK cells was Prostaglandin D2 (PGD2). PGD2 downregulated the expression of ZNF521 to decrease profibrotic protein synthesis. Furthermore, we confirmed the anti-endometrial fibrosis effect of eNK cells and its mechanism in an IUA-like murine model. These findings reveal an important role of eNK cells in endometrial homeostasis and provide potential therapeutic approaches for IUA patients.
A Novel Efficient Algorithm for Common Variants Genotyping from Low-Coverage Sequencing Data
Authors: Zhang Shixuan , Xiao Kanglong , He Xinyi , Hao Meng , Ma Yanyun , Tian Yuxin , Jin Li , Li Yi , Wang Jiucun , Wang Yi 
Published: December 2024

AbstractLow-coverage whole-genome sequencing (LC-WGS) combined with imputation represents a cost-effective genotyping strategy for genome-wide association studies (GWAS) in population genetics. In this study, the Limpute algorithm was developed specifically for genotyping from low-coverage sequencing data, it extracts variant information from low-coverage sequencing data by the novel virtual probes and subsequently performs imputation through cross-reference between samples. Compared to the currently dominant algorithm for low-coverage sequencing data, GLIMPSE2, Limpute achieved similar imputation performance within common variants (r2>0.87) while the GLIMPSE2 has a runtime approximately five times longer than that of the Limpute. Furthermore, to fully evaluate the accuracy of genotype imputation by Limpute, we utilized high-coverage whole-genome sequencing data (30x), microarray data, and high-coverage whole-exome sequencing data (30x) as validation sets respectively. The results demonstrated that Limpute has a good imputation performance for common variants using low-coverage sequencing data (1x: r2> 0.87; 3x: r2> 0.92; 5x: r2> 0.93). In summary, we present a highly efficient, low-cost algorithm for genotyping from low-coverage sequencing data, offering substantial support for genetic research.
Cystic fibrosis risk variants confer protection against inflammatory bowel disease
Authors: Yu Mingrui , Zhang Qian , Yuan Kai , Sazonovs Aleksejs , Stevens Christine , Fachal Laura ,   the International Inflammatory Bowel Disease Genetics Consortium, Anderson Carl A. , Daly Mark J. , Huang Hailiang 
Published: December 2024

AbstractGenetic mutations that yield defective cystic fibrosis transmembrane regulator (CFTR) protein cause cystic fibrosis, a life-limiting autosomal recessive Mendelian disorder. A protective role ofCFTRloss-of-function mutations in inflammatory bowel disease (IBD) has been suggested, but its evidence has been inconclusive and contradictory. Here, leveraging the largest IBD exome sequencing dataset to date, comprising 38,558 cases and 66,945 controls in the discovery stage, and 35,797 cases and 179,942 controls in the replication stage, we established a protective role of CF-risk variants against IBD based on evidence from the association test ofCFTRdelF508 (p-value=8.96E-11) and the gene-based burden test of CF-risk variants (p-value=3.9E-07). Furthermore, we assessed variant prioritization methods, including AlphaMissense, using clinically annotated CF-risk variants as the gold standard. Our findings highlight the critical and unmet need for effective variant prioritization in gene-based burden tests.