bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Effectiveness of Nirsevimab in Reducing Pediatric RSV Hospitalizations in Spain
Authors: Jimeno S. , Peláez A. , Labourt A. , Acuña F. , Linares L. , Llana Martín I. , Calle A , Natalini Martínez S. 
Published: September 2024

AbstractBackground and objectiveRespiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Nirsevimab has demonstrated to be a promise tool for preventing severe RSV disease. Although clinical trials have demonstrated the efficacy of Nirsevimab in preventing severe RSV disease, evidence regarding its performance in real-world clinical settings is still limited due to its recent introduction. This study aims to fill this knowledge gap by evaluating the impact of Nirsevimab in a cohort of infants and determining its effectiveness in reducing the burden of RSV disease.MethodsRetrospective study of RSV hospitalizations in children under six months of age, between October 1stand March 31st, across four seasons: pre-COVID (2018-2019), COVID (2019-2020), post-COVID pre-Nirsevimab (2022-2023), and Nirsevimab season (2023-2024).ResultsNirsevimab has demonstrated significant efficacy in reducing RSV-related hospitalizations in infants under six months of age. During the 2023/24 season, following the introduction of Nirsevimab, there was a substantial reduction in RSV-related lower respiratory tract infection (LRTI) hospitalizations. Among infants under 3 months of age, hospitalizations decreased by 79.3% (IRR: 0.21, 95% CI: 0.12–0.34). In infants aged 3 to 6 months, there was a 66.9% reduction (IRR: 0.33, 95% CI: 0.15– 0.64). Additionally, Nirsevimab decreased the severity of RSV cases with LRTI who required support of equipment for sanitary use further reducing overall healthcare burden.ConclusionThese results underscore Nirsevimab’s vital role in preventing severe RSV infections and hospitalizations, especially among the most vulnerable infants, positioning it as a critical advancement in pediatric respiratory care.
Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort
Authors: Kuo Pei-Lun , Moore Ann Zenobia , Tanaka Toshiko , Belsky Daniel W , Lu Ake Tzu-Hui , Horvath Steve , Bandinelli Stefania , Ferrucci Luigi 
Published: September 2024

AbstractsImportanceCross-sectional assessment of epigenetic clocks provides information on the pace of aging. Whether longitudinal acceleration or deceleration of epigenetic clocks over time provides additional mortality prediction is unknown.ObjectiveTo test the independent associations of baseline levels and longitudinal changes in epigenetic clocks with mortalityDesignLongitudinal studySettingInCHIANTI, a population-based study of community dwelling individuals in Tuscany, Italy.Participants699 InCHIANTI study participants aged 21-95 years at baseline with longitudinal measurements of DNA methylation.ExposureBaseline levels and longitudinal changes in seven epigenetic clocks, including two first-generation clocks developed using chronological age for reference (Hannum Clock, Horvath Clock), three second-generation clocks developed using time-to-death for references (DNAmPhenoAge, DNAmGrimAge, DNAmGrimAge Version 2), and two third-generation clocks developed using longitudinal rate of change of multiple phenotypes for reference (DunedinPOAm_38, DunedinPACE).Main Outcomes and MeasuresMortality was the primary outcome. Cox regression was used to estimate independent associations of baseline and longitudinal changes in epigenetic clocks with mortality.ResultsAdjusting for age, sex, study sites, and epigenetic clock at the baseline, longitudinal changes of the following epigenetic clocks were associated with mortality: Hannum clock (aHR = 1.14, 95% CI:[1.03, 1.26]), DNAmPhenoAge (aHR = 1.23, 95% CI: [1.10,1.37]), DNAmGrimAge (aHR = 1.13, 95% CI: [1.02,1.26]), DNAmGrimAge Version 2 (aHR = 1.18, 95% CI:[1.06,1.31]), and DunedinPOAm_38 (aHR = 1.15, 95%CI: [1.01,1.30]).Conclusions and RelevanceOur findings confirm that epigenetic clocks capture a dimension of health that is predictive of mortality and add the notion that time changes of epigenetic age reflect changes in health that additionally and independently contribute to mortality prediction. Future studies should test whether interventions that slow down the rate of epigenetic aging are associated with longer healthspan and lifespan.Key PointsQuestion: Is the rate of change in epigenetic clock associated with differential mortality?Findings: In 699 adults with followed for up to 24 years, faster longitudinal changes in epigenetic clocks (Hannum clock, DNAmPhenoAge, DNAmGrimAge, DNAmGrimAge version 2, DunedinPOAm_38, DunedinPACE) were significantly associated with higher mortality, independent of baseline epigenetic age and other confounders.Meaning: Independent of chronological age, epigenetic clock and change over time of epigenetic clock independently predicted the risk of death. Interventions that slow down the pace of epigenetic aging may enhance healthy longevity.
Accuracy of Online Symptom-Assessment Applications, Large Language Models, and Laypeople for Self-Triage Decisions: A Systematic Review
Authors: Kopka Marvin , von Kalckreuth Niklas , Feufel Markus A. 
Published: September 2024

AbstractSymptom-Assessment Application (SAAs, e.g., NHS 111 online) that assist medical laypeople in deciding if and where to seek care (self-triage) are gaining popularity and their accuracy has been examined in numerous studies. With the public release of Large Language Models (LLMs, e.g., ChatGPT), their use in such decision-making processes is growing as well. However, there is currently no comprehensive evidence synthesis for LLMs, and no review has contextualized the accuracy of SAAs and LLMs relative to the accuracy of their users. Thus, this systematic review evaluates the self-triage accuracy of both SAAs and LLMs and compares them to the accuracy of medical laypeople. A total of 1549 studies were screened, with 19 included in the final analysis. The self-triage accuracy of SAAs was found to be moderate but highly variable (11.5 – 90.0%), while the accuracy of LLMs (57.8 – 76.0%) and laypeople (47.3 – 62.4%) was moderate with low variability. Despite some published recommendations to standardize evaluation methodologies, there remains considerable heterogeneity among studies. The use of SAAs should not be universally recommended or discouraged; rather, their utility should be assessed based on the specific use case and tool under consideration.
Parasitic and Commensal interactions among Mimiviruses, Sputnik-like virophages, and Transpovirons: A theoretical and dynamical systems approach
Authors: Ortega-Atehortúa Emmanuel , Rivera Parra Nicole , Rodríguez Boris A. , Machado-Rodríguez Gloria , Arboleda Rivera Juan Camilo 
Published: September 2024

AbstractGiant viruses have been in the scope of virologists since 2003 when they were isolated fromAcanthamoebaspp. Giant viruses, in turn, get infected by another virus named virophage and a third biological entity that corresponds to a transpoviron which can be found in the capsids of giant and virophage viruses. So far, transpovirons seem to behave as commensal entities while some virophages exhibit commensal behavior under laboratory conditions. To study the system’s behavior, we used a theoretical approximation and developed an ordinary differential equation model. The dynamical analysis showed that the system exhibits an oscillatory robust behavior leading to a hyperparasitic Lotka-Volterra dynamic. But the biological mechanism that underlines the transpoviron persistence over time remains unclear and its status as a commensal entity needs further assessment. Also, the ecological interaction that leads to the overall coexistence of the three viral entities needs to be further studied.
Magnetic Protein Aggregates Generated by Supramolecular Assembly of Ferritin Cages - A Modular Strategy for the Immobilization of Enzymes
Authors: Ölçücü Gizem , Wollenhaupt Bastian , Kohlheyer Dietrich , Jaeger Karl-Erich , Krauss Ulrich 
Published: September 2024

AbstractEfficient and cost-effective immobilization methods are crucial for advancing the utilization of enzymes in industrial biocatalysis. To this end,in vivoimmobilization methods relying on the completely biological production of immobilizates represent an interesting alternative to conventional carrier-based immobilization methods. In this contribution, we present a novel immobilization strategy utilizingin vivoproduced, magnetic protein aggregates (MPAs). MPA production is facilitated by the expression of gene fusions consisting of genes encoding for the yellow fluorescent protein variant citrine and variants of the iron storage protein ferritin, including a magnetically enhanced ferritin mutant fromEscherichia coli.Expression of the gene fusions allows supramolecular assembly of the fusion proteinsin vivo, which is driven by citrine-dependent dimerization of ferritin cages. Upon cell lysis, the assemblies coalesce in solution to form MPAs. The fusion of the mutantE. coliferritin to citrine yields fluorescent, insoluble protein aggregates that display magnetic properties, verified by their attraction to neodymium magnets. We further demonstrate that these novel, fullyin vivoproduced protein aggregates can be magnetically purified without the need forex vivoiron-loading. Utilizing a bait/prey strategy, MPAs were functionalized by the post-translational attachment of an alcohol dehydrogenase to the MPA particles to enable proof-of-concept for enzyme immobilization, giving rise to catalytically-active magnetic protein aggregates (CatMPAs). The resulting (Cat)MPAs could easily be obtained from crude cell extracts via centrifugation, or purified using magnetic columns, and exhibited superior stability. The strategy presented here therefore represents a highly modular method to produce magnetic enzyme immobilizates which can be obtained with high purity.
TheDrosophilaEstrogen-Related Receptor promotes triglyceride storage within the larval fat body
Authors: Fasteen Tess D. , Hernandez Melody R. , Policastro Robert A. , Sterrett Maria C. , Zenter Gabriel E. , Tennessen Jason M. 
Published: September 2024

ABSTRACTThe Estrogen-Related Receptor (ERR) family of nuclear receptors (NRs) serve key roles in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, ERR activity promotes TAG storage during the post-embryonic growth phase, with loss-of-function mutations in mouseEsrraandDrosophila melanogaster dERRinducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation within adipose tissue remains poorly understood, as previous transcriptomic and metabolomic studies relied on whole animal analyses. Here we address this shortcoming by using tissue-specific approaches to examine the role of dERR in regulating lipid metabolism within theDrosophilalarval fat body. We find that dERR autonomously promotes TAG accumulation within fat body cells and regulates expression of genes involved in glycolysis, β-oxidation, and mevalonate metabolism. As an extension of these results, we not only discovered thatdERRmutant fat bodies exhibit decreased expression of known dHNF4 target genes but also found that dHNF4 activity is decreased indERRmutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with developmental growth and hint at a conserved mechanism by which ERR and HNF4 homologs coordinately regulate metabolic gene expression.
Lower perceived stress enhances neural synchrony in perceptual and attentional cortices during naturalistic processing
Authors: Craig J. , Matisz C. , Klamer K. , Haines C. , Sullivan K. , Ekstrand C. 
Published: September 2024

AbstractPerceived stress is the subjective appraisal of the level of stress experienced by an individual in response to external or internal demands. Recent research on perceived stress has highlighted its role in influencing cognition, leading to a disruption in cognitive processes, such as emotional processing, attention, and perception. However, most neuroimaging studies examining stress have used static stimuli (e.g., still images) that do not encapsulate real-life multimodal processing in the brain. The current research uses data from the Naturalistic Neuroimaging Database (v2.0; Aliko et al., 2020) to examine differences in neural synchrony (as measured by intersubject correlations; ISCs) associated with perceived stress using functional magnetic resonance imaging (fMRI). We evaluated how self-reported perceived stress levels influence neural synchrony patterns in response to different naturalistic stimuli by examining the differences in neural synchrony between individuals with low and high perceived stress levels. We determined that lower perceived stress was observed with greater neural synchrony areas associated with perceptual and attention processing, including the lateral occipital cortex, superior temporal gyrus, superior parietal lobule, orbital frontal cortex, and the occipital pole. These results indicate that high levels of perceived stress heavily alter neural processing of complex audiovisual stimuli. Together, these results provide evidence that perceived stress influences cognitive processing in everyday life.
Cognitive effects of early life exposure to PCBs: Sex-specific behavioral, hormonal and neuromolecular mechanisms involving the brain dopamine system
Authors: Hilz Emily N. , Schnurer Cameron , Bhamidipati Swati , Deka Jahnabi , Thompson Lindsay M. , Gore Andrea C. 
Published: September 2024

AbstractEndocrine-disrupting chemicals (EDCs) are environmental toxicants that disrupt hormonal and neurodevelopmental processes. Among these chemicals, polychlorinated biphenyls (PCBs) are particularly concerning due to their resistance to biodegradation and tendency to bioaccumulate. PCBs affect neurodevelopmental function and disrupt the brain’s dopamine (DA) system, which is crucial for attentional, affective, and reward processing. These disruptions may contribute to the rising prevalence of DA-mediated neuropsychiatric disorders such as ADHD, depression, and substance use disorders. Notably, these behaviors are sexually dimorphic, in part due to differences in sex hormones and their receptors, which are targets of estrogenic PCBs. Therefore, this study determined effects of early life PCB exposure on behaviors and neurochemistry related to potential disruption of dopaminergic signaling. Male and female Sprague Dawley rats were exposed to PCBs or vehicle perinatally and then underwent a series of behavioral tests, including the sucrose preference test to measure affect, conditioned orienting to assess incentive-motivational phenotype, and attentional set-shifting to evaluate cognitive flexibility and response latency. Following these tests, rats were euthanized, and we measured serum estradiol (E2), midbrain DA cells, and gene expression in the midbrain. Female rats exposed perinatally to A1221 exhibited decreased sucrose preference, and both male and female A1221 rats had reduced response latency in the attentional set-shifting task compared to vehicle counterparts. Conditioned orienting, serum estradiol (E2), and midbrain DA cell numbers were not affected in either sex; however, A1221-exposed male rats displayed higher expression of estrogen receptor alpha (Esr1) in the midbrain and non-significant effects on other DA-signaling genes. Additionally, E2 uniquely predicted behavioral outcomes and DAergic cell numbers in A1221-exposed female rats, whereas DA signaling genes were predictive of behavioral outcomes in males. These data highlight sex-specific effects of A1221 on neuromolecular and behavioral phenotypes.
Knowledge and experiences of adolescent girls and young women in the use of sexual reproductive health and HIV services at health facilities in Maputo City, Mozambique
Authors: Muchanga Vasco A. , Huo Luisa , Kampa Kathryn T. , Chilundo Baltazar , Munguambe Khátia R. , Moon Troy D. 
Published: September 2024

AbstractBackgroundKnowledge and use of sexual reproductive health and human immunodeficiency virus (SRH and HIV) services are crucial for the prevention of pregnancy and sexually transmitted infections (STIs) among adolescent girls and young women (AGYW). This study aims to assess the knowledge and perceptions of AGYW about the SRH and HIV services offered in health facilities in Maputo, Mozambique.Material and methodsA cross-sectional descriptive study was conducted based on exit surveys with AGYW held at Zimpeto and 1° de Junho Health Facilities in Maputo City, between May 1, and June 9, 2023. Data were analyzed through descriptive statistics, t-test and ANOVA, using SPSS version 20.Results590 AGYW, aged 15-24 years of age, were included in the study. In general, knowledge of SRH and HIV services was fairly high, with knowledge of each specific service offered ranging between 38% and 97%. Knowledge about SRH and HIV services differed depending on the health facility where the AGYW sought SRH and HIV services; the participant’s age; their occupation; their religion, and who they lived with. Counseling services were the most commonly reported services attended, with >90% of participants reporting having received counseling for each of the following: STI and HIV and pregnancy prevention, sexuality, and safer sex practices. The quality of SRH and HIV services, and attitudes of the providers were considered good by >90% of AGYW. Roughly 95% of AGYW at Zimpeto Health Facility were either “satisfied” or “very satisfied”. Whereas at 1° de Junho Health Facility, only roughly 75% of AGYW were either “satisfied” or “very satisfied”, and roughly 20% of AGYW were “little satisfied that their needs had been met that day.ConclusionsAmong AGYW there is high levels of knowledge about counseling services in contrast to diagnostics, treatment and clinical care. Specific attention should be given to ensuring appropriate physical infrastructure, such as dedicated adolescent friendly spaces and comfortable seating, and targeted interventions designed and implemented for those health facilities’s identified. Targeted interventions should be designed and implemented for those HF’s identified with lower AGYW perceived quality of service delivery.
Decoding Specificity of Cyanobacterial MysDs in Mycosporine-Like Amino Acid Biosynthesis through Heterologous Expression inSaccharomyces cerevisiae
Authors: Zheng Xiaoyou , Xie Peifeng , Cai Andrew Chen , Jiang Yuze , Huang Sirui , Ma Xiaochong , Su Honghao , Wang Boxiang 
Published: September 2024

AbstractMycosporine-like amino acids (MAAs) are potent natural UV-protectants, but their industrial production is hindered by efficiency and sustainability issues of large-scale extraction of their native hosts. Heterologous expression of MAA biosynthesis pathway genes in chassis organisms provides a promising alternative route, though the substrate promiscuity of the ATP-grasp ligase MysD complicates the biosynthesis of specific MAAs. In this study, we developed aSaccharomyces cerevisiaestrain with enhanced capacity of producing mycosporine-glycine (MG), through genomic expression of biosynthesis pathway genes and knockout of competing pathway genes. This strain serves as an efficient MysD expression platform, which converts MG into shinorine and porphyra-334. Through structural modelling, site-directed mutagenesis and mutant characterization, we identified two residues on the omega-loop of MysD involved in determining product specificity. We further characterized the product specificity of 20 MysDs from diverse cyanobacterial lineages and confirmed the residue pattern-product specificity correlation. Our findings provide guidance for screening, selecting, and designing novel MysDs for industrial-scale MAA production through heterologous expression.
Genetic code expansion reveals site-specific lactylation in living cells reshapes protein function
Authors: Shao Chang , Tang Shuo , Yu Siqin , Liu Chenguang , Wan Tianyan , He Zimeng , Yuan Qi , Zhang Yueyang , Zhan Mengru , Zhang Hanqing , Wan Ning , Wu Shihan , Tan Ren Xiang , Hao Haiping , Ye Hui , Wang Nanxi 
Published: September 2024

AbstractStill in its infancy, the functions of lactylation remain elusive. To address this, we established a comprehensive workflow for lactylation studies that integrates the discovery of lactylation sites with proteomics, the expression of site-specifically lactylated proteins in living cells via genetic code expansion (GCE), and the evaluation of the resulting biological consequences. Specifically, we developed a wet-and-dry-lab combined proteomics strategy, and identified highly conserved lactylation at ALDOA-K147. Driven by its potential biological significance, we site-specifically expressed this lactylated ALDOA in mammalian cells and interrogated the biological changes. We discovered that it not only inhibited enzyme activity but also elicited gain-of-function effects——it dramatically reshaped the functionality of ALDOA by improving stability, enhancing nuclear translocation and affecting gene expression. Further, we demonstrated broad applicability of this workflow to study distinct histone lactylation sites. Together, we anticipate its wide uses in elucidating causative links between site-specific lactylation and target-centric or cell-wide changes.
Stress granule formation enables anchorage-independence survival in cancer cells
Authors: Yang Seungwon , Aulas Anaïs , Anderson Paul J. , Ivanov Pavel 
Published: September 2024

AbstractStress granules (SGs) are dynamic cytoplasmic structures assembled in response to various stress stimuli that enhance cell survival under adverse environmental conditions. Here we show that SGs contribute to breast cancer progression by enhancing the survival of cells subjected to anoikis stress. SG assembly is triggered by inhibition of Focal Adhesion Kinase (FAK) or loss of adhesion signals. Combined proteomic analysis and functional studies reveal that SG formation enhances cancer cell proliferation, resistance to metabolic stress, anoikis resistance, and migration. Importantly, inhibiting SG formation promotes the sensitivity of cancer cells to FAK inhibitors being developed as cancer therapeutics. Furthermore, we identify the Rho-ROCK- PERK-eIF2α axis as a critical signaling pathway activated by loss of adhesion signals and inhibition of the FAK-mTOR-eIF4F complex in breast cancer cells. By triggering SG assembly and AKT activation in response to anoikis stress, PERK functions as an oncoprotein in breast cancer cells. Overall, our study highlights the significance of SG formation in breast cancer progression and suggests that therapeutic inhibition of SG assembly may reverse anoikis resistance in treatment-resistant cancers such as triple-negative breast cancer (TNBC).HighlightsEither anoikis stress or loss of adhesion induce stress granule (SG) formationThe Rho-ROCK-PERK-eIF2α axis is a crucial signaling pathway triggered by the absence of adhesion signals, leading to the promotion of SG formation along with the inhibition of the FAK- AKT/mTOR-eIF4F complex under anoikis stress.PERK functions as an oncogene in breast cancer cells, initiating SG formation and activating AKT under anoikis stress.Inhibiting SG formation significantly enhances the sensitivity to Focal Adhesion Kinase (FAK) inhibitors, suggesting a potential for combined therapy to improve cancer treatment efficacy.