bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between umbilical cord torsion and Doppler parameters of umbilical artery: a single-center retrospective case-control study
Authors: Li Yuan , Zhang Dirong , Shi Yu 
Published: November 2023

AbstractObjectiveTo explore the correlation between umbilical cord torsion and the changes of umbilical artery Doppler parameters, to provide valuable information for prenatal ultrasound screening of umbilical cord torsion, and to explore the possible mechanism of umbilical artery Doppler parameters changes during umbilical cord torsion. Method:The subjects were 962 pregnant women who were discharged from our hospital from January 2015 to November 2021 and were eligible for inclusion (415 in the case group and 547 in the control group). The measurement data of umbilical artery Doppler parameters (PSV, S/D, RI, PI) were collected from 21 to 40 weeks of gestation, and the differences among the above parameters were statistically analyzed.ResultsThe peak systolic velocity (PSV) of umbilical artery is positively correlated with gestational age, while the Doppler resistance parameters (S/D, RI, PI) of umbilical artery are negatively correlated with gestational age. The mean values of umbilical artery Doppler parameters (PSV, S/D, RI, PI) in the case group were significantly lower than those in the control group of the same pregnancy age (P < 0.05).ConclusionThe decrease of Doppler parameters of umbilical artery in late pregnancy is significantly related to umbilical cord torsion, which may be a clue for prenatal ultrasound screening of umbilical cord torsion. The Doppler parameters of umbilical artery during umbilical cord torsion are consistent with the basic principle of Doppler parameters change after vascular stenosis in other parts of the human body. It is necessary to conduct multicenter prospective study in the future.
Genomic Insights into the Shared and Distinct Genetic Architecture of Cognitive Function and Schizophrenia
Authors: Wootton Olivia , Shadrin Alexey A. , Bjella Thomas , Smeland Olav B. , van der Meer Dennis , Frei Oleksandr , O’Connell Kevin S , Ueland Torill , Andreassen Ole A. , Stein Dan J. , Dalvie Shareefa 
Published: November 2023

AbstractCognitive impairment is a major determinant of functional outcomes in schizophrenia, and efforts to understand the biological basis of cognitive dysfunction in the disorder are ongoing. Previous studies have suggested genetic overlap between global cognitive ability and schizophrenia, but further work is needed to delineate the shared genetic architecture. Here, we apply genomic structural equation modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank (UKB). We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). We identified three broad factors (visuo-spatial, verbal analytic and decision/reaction time) that underly the genetic correlations between the UKB cognitive tests. Global genetic correlations showed a significant but moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found evidence of substantial polygenic overlap between each cognitive factor and schizophrenia but show that most loci shared between the latent cognitive factors and schizophrenia have unique patterns of association with the cognitive factors. Biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we find that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptom dimensions. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.
Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression
Authors: Schweizer Lisa , Krishnan Rahul , Shimizu Aasa , Metousis Andreas , Kenny Hilary , Mendoza Rachelle , Nordmann Thierry M. , Rauch Sarah , Kelliher Lucy , Heide Janna , Rosenberger Florian A. , Bilecz Agnes , Borrego Sanaa Nakad , Strauss Maximillian T. , Thielert Marvin , Rodriguez Edwin , Müller-Reif Johannes B. , Chen Mengjie , Yamada S. Diane , Mund Andreas , Lastra Ricardo R. , Mann Matthias , Lengyel Ernst 
Published: November 2023

AbstractSerous borderline tumors (SBT) are epithelial neoplastic lesions of the ovaries that commonly have a good prognosis. In 10-15% of cases, however, SBT will recur as low-grade serous cancer (LGSC), which is deeply invasive and responds poorly to current standard chemotherapy1,2,3. While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood4. Here, we integrate spatial proteomics5with spatial transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastasis at the molecular level in both the stroma and the tumor. We show that the transition of SBT to LGSC occurs in the epithelial compartment through an intermediary stage with micropapillary features (SBT-MP), which involves a gradual increase in MAPK signaling. A distinct subset of proteins and transcripts was associated with the transition to invasive tumor growth, including the neuronal splicing factor NOVA2, which was limited to expression in LGSC and its corresponding metastasis. An integrative pathway analysis exposed aberrant molecular signaling of tumor cells supported by alterations in angiogenesis and inflammation in the tumor microenvironment. Integration of spatial transcriptomics and proteomics followed by knockdown of the most altered genes or pharmaceutical inhibition of the most relevant targets confirmed their functional significance in regulating key features of invasiveness. Combining cell-type resolved spatial proteomics and transcriptomics allowed us to elucidate the sequence of tumorigenesis from SBT to LGSC. The approach presented here is a blueprint to systematically elucidate mechanisms of tumorigenesis and find novel treatment strategies.
Integrating stimulus-organism-response model and theory of planned behavior to explore athletes’ intention to receive the COVID-19 vaccine booster—A moderated mediation model
Authors: Zhan Wenpeng , Deng Qianting , Nguyen Van Bac , Duc Anh Tran Phan , Na Phan Danh , Shia An-Shin , Ku Gordon Chih-Ming 
Published: November 2023

AbstractThis study aims to investigate the factors influencing athletes’ intention to receive the COVID-19 vaccine booster in Mainland China by integrating the stimulus-organization-response (SOR) model and theory of planned behavior (TPB) as the theoretical framework. Purposive sampling was used to select respondents from the National Games of the People’s Republic of China. Hard-copy questionnaires were utilized to collect data, resulting in 981 valid responses. Descriptive analysis and partial least squares structural equation modeling were used to analyze the data. The findings reveal that athletes’ subjective norm and knowledge significantly influence attitude, commitment, and perceived behavioral control. Attitude, commitment, and perceived behavioral control are verified as full mediators between subjective norm, knowledge, and intention to receive the COVID-19 vaccine booster. Knowledge to commitment is the most powerful path to predict athletes’ intention to receive the COVID-19 vaccine booster. Motivation moderates the relationships between knowledge, attitude, commitment, and perceived behavioral control. The integrating model’s explanatory power is 83.2%. Athletes’ knowledge is crucial in shaping a positive attitude, commitment, and perceived control, enhancing their intention to get the COVID-19 vaccine booster.
Atrial Fibrillation Catheter Ablation among Cancer Patients: Utilization Trends and In-Hospital Outcomes
Authors: Margolis Gilad , Goldhaber Ofir , Kazatsker Mark , Kobo Ofer , Roguin Ariel , Leshem Eran 
Published: November 2023

ABSTRACTBACKGROUNDAtrial fibrillation (AF) catheter ablation in cancer patients was evaluated in very few studies. We aimed to investigate trends of utilizations as well as in-hospital outcomes of AF catheter ablation procedures among cancer patients, in a large inpatient US registry.METHODS AND RESULTSUsing the National Inpatient Sample (NIS) database, patients who underwent AF catheter ablations in the US between 2012 and 2019 were identified using ICD-9/10 codes. Sociodemographic, clinical data, in-hospital procedures and outcomes as well as in-hospital mortality and length-of-stay (LOS) were collected. Baseline characteristics and in-hospital outcomes were compared between patients with and without cancer. An estimated total of 67915 patients underwent AF catheter ablation between 2012-2019 in the US. Of them, 950 (1.4%) had cancer diagnosis. Compared with non-cancer patients, patients with cancer were older, had higher Charlson Comorbidity Index, as well as CHA2DS2-VASc and ATRIA bleeding indices scores.Higher rate of total complications was observed in cancer patients (10.5% vs 7.9, p<0.001) driven mainly by more bleeding and infectious complications. LOS was also significantly longer in cancer patients (4.9 ± 5.8 vs. 2.7 ± 3.0 days, p<0.001). However, no significant differences in cardiac or neurological complications as well as in-hospital mortality rates were observed and were relatively low in both groups.CONCLUSIONSAF catheter ablation in cancer patients is associated with higher bleeding and infectious complication rates, but not with increased cardiac complications or in-hospital mortality rates in a nationwide, all-comer registry.
Human Brucellosis in Iraq: what does a spatiotemporal data analysis from 2007-2018 reveal?
Authors: Mustafa Ali Hazim , Khaleel Hanan Abdulghafoor , Al-Lami Faris 
Published: November 2023

AbstractBackgroundBrucellosis is both endemic and enzootic in Iraq, resulting in long-term morbidity for humans as well as economic loss. No previous study of the spatial and temporal patterns of brucellosis in Iraq was done to identify potential clustering of cases.ObjectivesThis study aims to detect the spatial and temporal distribution of human brucellosis in Iraq and identify any changes that occurred from 2007 to 2018.MethodsA descriptive cross-sectional study using secondary data from the Communicable Diseases Control Center / Ministry of Health surveillance section. We used Moran’s I, local Getis-Ord’s Gi*, and the local indicators of spatial association (LISA) to detect the spatial distribution of the data. The data was analyzed using Excel software and the Quantum GIS (QGIS) version 2.18.20 (Steiniger and Hunter, 2013).Results50,621 human brucellosis cases were reported during the 12-year study period. Human brucellosis persisted annually in Iraq across the study period with no specific temporal clustering of cases. In contrast, spatial clustering was predominant in the Northern region of Iraq.ConclusionThere were significant differences in the geographic distribution of brucellosis. The number of cases is highest in the north and northeast of the country, which has borders with nearby countries. In addition, people in these areas depend more on locally made dairy products, which can be inadequately pasteurized. Despite the lack of significant temporal clustering of cases, the highest number of cases were reported during Summer and Spring.RecommendationsConsidering these patterns when allocating resources to combat this disease, determining public health priorities, and planning prevention and control strategies is important.
Bacteriocin Distribution Patterns inEnterococcus faeciumandEnterococcus lactis:Bioinformatic Analysis Using a Tailored Genomics Framework
Authors: Tedim Ana P. , Almeida-Santos Ana C. , Lanza Val F. , Novais Carla , Coque Teresa M. , Freitas Ana R. , Peixe Luísa 
Published: November 2023

ABSTRACTMultidrug-resistantEnterococcus faeciumrepresent a major concern due to their ability to thrive in diverse environments and cause life-threatening infections. While antimicrobial resistance and virulence mechanisms have been extensively studied, the contribution of bacteriocins toE. faecium’s adaptability remains poorly explored.E. faecium, within the Bacillota phylum, is a prominent bacteriocin producer. Here, we developed a tailored database of 76 Bacillota bacteriocins (217 sequences, including 40 novel bacteriocins) and applied it to uncover bacteriocin distribution patterns in 997 quality-filteredE. faeciumandEnterococcus lactis(formerE. faeciumclade B) genomes. Curated using computational pipelines and literature mining, our database demonstrates superior precision versus leading public tools in identifying diverse bacteriocins. Distinct bacteriocin profiles emerged betweenE. faeciumandE. lactis, highlighting species-specific adaptations.E. faeciumstrains from hospitalized patients were significantly enriched for bacteriocins asentA,bac43,bacAS5 andbacAS11. These bacteriocins strongly associated with antibiotic resistance, particularly vancomycin and ampicillin, and Inc18rep2_pRE25-derivative plasmids, classically associated with vancomycin resistance transposons. Our integrated genomic and epidemiological analysis elucidates meaningful connections between bacteriocin determinants, antimicrobial resistance, mobile genetic elements, and ecological origins inE. faecium. This work significantly expands the knowledge on the understudied bacteriocin diversity in opportunistic enterococci, revealing their contribution to environmental adaptation. Further characterization of strain-level bacteriocin landscapes could inform strategies to combat high-risk clones. Overall, these insights provide a framework for unravelling bacteriocins’ therapeutic and biotechnological potential.
Fusion dynamics and size-dependent droplet microstructure in ssDNA mediated protein phase separation
Authors: Bian Yunqiang , Li Wenfei 
Published: November 2023

AbstractBiomolecular cocondensation involving proteins and nucleic acids has been recognized to play crucial roles in genome organization and transcriptional regulation. However, the biophysical mechanisms underlying the fusion dynamics and microstructure evolution of the droplets during the early stage of liquid-liquid phase separation (LLPS) remain elusive. In this work, we study the phase separation of linker histone H1, which is among the most abundant chromatin proteins, in the presence of single-stranded DNA (ssDNA) capable of forming G-quadruplex structures by using residue-resolved molecular dynamics simulations. Firstly, we uncovered a kinetic bottleneck step in the droplet fusion. Productive fusion events are triggered by the formation of ssDNA mediated electrostatic bridge within the contacting zone of two droplets. Secondly, the simulations revealed a size-dependence of the droplet microstructure and stoichiometry. With droplet growth, its microstructure evolves as driven by the maximization of the electrostatic contacts between ssDNA and the highly charged segment of H1. Finally, we showed that the folding of ssDNA to G-quadruplex promotes LLPS by increasing the multivalency and strength of protein-DNA interactions. These findings provided new mechanistic insights into the microstructure and growth dynamics of the biomolecular droplets formed during the early stage of the ssDNA-protein cocondensation.
The AccelerAge framework: A new statistical approach to predict biological age based on time-to-event data
Authors: Sluiskes Marije , Goeman Jelle , Beekman Marian , Slagboom Eline , van den Akker Erik , Putter Hein , Rodríguez-Girondo Mar 
Published: November 2023

AbstractAging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While chronological age serves as a strong risk factor for age-related health conditions, considerable heterogeneity exists in the aging trajectories of individuals, suggesting that biological age may provide a more nuanced understanding of the aging process. However, the concept of biological age lacks a clear operationalization, leading to the development of various biological age predictors without a solid statistical foundation. This paper addresses these limitations by proposing a comprehensive operationalization of biological age, introducing the “AccelerAge” framework for predicting biological age, and introducing previously underutilized evaluation measures for assessing the performance of biological age predictors. The AccelerAge framework, based on Accelerated Failure Time (AFT) models, directly models the effect of candidate predictors of aging on an individual’s survival time, aligning with the prevalent metaphor of aging as a clock. We compare predictors based on the AccelerAge framework to a predictor based on the GrimAge predictor, which is considered one of the best-performing biological age predictors, using simulated data as well as data from the UK Biobank and the Leiden Longevity Study. Our approach seeks to establish a robust statistical foundation for biological age clocks, enabling a more accurate and interpretable assessment of an individual’s aging status.
Nonribosomal peptide synthetases require dynamic interaction between modular domains
Authors: Peng Ye-Jun , Zeng Xiaoli , Chen Yuxing , Zhou Cong-Zhao , Miao Wei , Jiang Yong-Liang , Zhang Cheng-Cai 
Published: November 2023

AbstractNonribosomal peptide synthetases (NRPSs) are large multidomain enzymes for the synthesis of a variety of bioactive peptides in a modular and pipelined fashion. Here, we investigated how the condensation (C) domain and the adenylation (A) domain cooperate with each other for the efficient catalytic activity in microcystin NRPS modules. We solved two crystal structures of the microcystin NRPS modules, representing two newly identified conformations in the NRPS catalytic cycle. Our data reveals that the dynamic interaction between the C and the A domains in these modules are mediated by the conserved “RXGR” motif, and this interaction is important for the adenylation activity. Furthermore, the “RXGR” motif-mediated dynamic interaction and its functional regulation is prevalent in different NRPSs modules possessing both the A and the C domains. This study provides new insight into the catalytic mechanism of NRPSs and should inspire novel ideas in NRPS enzyme engineering in synthetic biology.
Roles of linker region flanked by transmembrane and peptidoglycan binding region of PomB in energy conversion of theVibrioflagellar motor
Authors: Miyamura Yusuke , Nishikino Tatsuro , Koiwa Hiroaki , Homma Michio , Kojima Seiji 
Published: November 2023

ABSTRACTThe energy converting complex of the sodium-driven flagellar motor in bacteria comprises two proteins, PomA and PomB, whose transmembrane regions form ion conducting channels and is called the stator complex. The transmembrane protein PomB is attached to the cell wall by its periplasmic region and has a plug segment following the transmembrane helix to prevent ion flux. PomB (Δ41-120), which lacks the periplasmic region from E41 to K120 immediately following its transmembrane region shows similar motility as that of wild-type PomB. In this study, three deletion mutants after the plug region, PomB (Δ61-120), PomB (Δ61-140), and PomB (Δ71-150), were generated and those deletion mutants were examined for their functionality. PomB (Δ61-120) conferred similar motility as that of the wild-type protein, whereas the other two mutants showed almost no motility in soft agar plate; however, we observed some swimming cells with speed similar to that of the wild-type cells. To observe dominance of wild-type proteins, we introduced the two PomB mutants into a wild-type strain, and its ability to swim was not affected by the mutants. Then, we purified the mutant PomAB complexes to confirm the stator formation. When we introduced the PomB mutations in the plug region, the reduced motility by the deletion was rescued, suggesting that the stator was activated. Our results indicate that the deletion prevents stator from transformation to an active form; however, the linker and plug regions from E41 to S150 are not essential for the motor function of PomB but are important for its regulation.IMPORTANCEThe stator complex of flagella consists of PomA and PomB proteins and interacts with the rotor complex. PomB has a peptidoglycan binding (PGB) domain to fix the stator for generation of torque. PomB is attached to the cell wall only when the stator is activated by interaction between the cytoplasmic region of PomA and the rotor protein FliG. The flexible linker of PomB, which is a naturally unfolded region, is flanked by the peptidoglycan-binding (PGB) domain and transmembrane region. The plug region, which interacts with the periplasmic loops of PomA to prevent activation of the stator, is located next to its transmembrane region. In this study, we reveal the role of the flexible linker in activation of the stator complex.
An EWS::FLI1 monoclonal antibody with multimodal utility and specificity for FLI1
Authors: Selvanathan Saravana , Toretsky Jeffrey 
Published: November 2023

AbstractEwing sarcoma (ES) is a rare tumor that affects children, adolescents, and young adults. This tumor has a high morbidity in all patients and for those who present with metastatic disease a high mortality. A canonical chromosomal translocation, either t(11;22)(q24;p12) or t(21;22)(q22;q12) leads to the fusion oncoproteins EWS::FLI1 or EWS::ERG in 95% of ES patients. We recognized a critical need for a stably sourced high affinity antibody that recognizes EWS::FLI1 with maximal specificity. We created and validated a hybridoma that produces a mouse derived monoclonal antibody that recognizes EWS::FLI1 in multiple molecular biology applications.
The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease
Authors: Pannafino Gianno , Chen Jun Jie , Mithani Viraj , Payero Lisette , Gioia Michael , Crickard J. Brooks , Alani Eric 
Published: November 2023

AbstractThe accurate segregation of homologous chromosomes during the Meiosis I reductional division in most sexually reproducing eukaryotes requires crossing over between homologs. In baker’s yeast approximately 80 percent of meiotic crossovers result from Mlh1-Mlh3 and Exo1 acting to resolve double-Holliday junction (dHJ) intermediates in a biased manner. Little is known about how Mlh1-Mlh3 is recruited to recombination intermediates and whether it interacts with other meiotic factors prior to its role in crossover resolution. We performed a haploinsufficiency screen in baker’s yeast to identify novel genetic interactors with Mlh1-Mlh3 using sensitizedmlh3alleles that disrupt the stability of the Mlh1-Mlh3 complex and confer defects in mismatch repair but do not disrupt meiotic crossing over. We identified several genetic interactions betweenMLH3andDMC1,the recombinase responsible for recombination between homologous chromosomes during meiosis. We then showed that Mlh3 physically interacts with Dmc1in vitroand at times in meiotic prophase when Dmc1 acts as a recombinase. Interestingly, restrictingMLH3expression to roughly the time of crossover resolution resulted in amlh3null-like phenotype for crossing over. Our data are consistent with a model in which Dmc1 nucleates a polymer of Mlh1-Mlh3 to promote crossing over.