bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADHD symptom reduction after following an FFD is associated with gut microbiome composition
Authors: Hontelez S , Guthrie M , Stobernack T , van Baarlen P , Rousseau C , Boks MP , Rodrigues Pereira R , Boekhorst J , Kleerebezem M 
Published: July 2024

AbstractAttention-deficit hyperactivity disorder (ADHD) is one of the most common childhood neuropsychiatric conditions. Both (epi)genetic and environmental factors are suggested to contribute to the aetiology of ADHD. In the last decade, nutrition has received considerable attention as potential environmental factor triggering ADHD behaviour. Studies applying a few-foods diet (FFD) can lead to behavioural improvements of at least 40% in 50-64% of children with ADHD. It is conceivable that the Microbiota-Gut-Brain (MGB) axis is involved in the mechanism of action underlying the behavioural improvements observed in children with ADHD after following the FFD. This study investigated potential associations between changes in ADHD symptoms in children that followed an FFD. We identified a significant association between microbiota composition and change in ADHD symptoms in food-associated ADHD.
The higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect
Authors: Andrews Daniel , Ducharme Simon , Chertkow Howard , Sormani Maria Pia , Collins D. Louis ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2024

AbstractINTRODUCTIONThe Phase 3 trial CLARITY AD found that lecanemab slowed cognitive decline by a statistically significant 27% vs. placebo. However, the subgroup analysis indicated a significant sex difference in the effect, and recent work has implied that lecanemab has either no or limited effectiveness in females. To resolve this ambiguity, we used simulations constrained by the trial design to determine whether the difference could be explained by known sex differences in Alzheimer’s progression, or as an isolated random event.METHODSSimulations were generated using linear mixed models of cognitive decline fit to data from ADNI participants who satisfied CLARITY AD inclusion criteria.RESULTSThe statistically nonsignificant 7.9% sex difference in cognitive decline rate observed in our selected ADNI participants does not explain the trial’s 31% sex difference in lecanemab’s effect. A ≥31% difference occurred randomly in only 12 of our 10,000 simulations, signifying a probability of 0.0012.DISCUSSIONOur results are consistent with those from CLARITY AD. Lecanemab likely affects females and males differently, but we cannot conclude that the drug is ineffective in females.
Fundamental limits to the effectiveness of traveler screening with molecular tests
Authors: Bubar Kate M. , Middleton Casey E. , Larremore Daniel B. , Gostic Katelyn M. 
Published: July 2024

AbstractDespite the appeal of screening travelers during emerging infectious disease outbreaks, evidence shows that syndromic and questionnaire-based programs are largely ineffective in preventing or delaying the geographic spread of infection. Molecular tests offer high sensitivity and specificity, and can detect infections earlier than symptom screening, suggesting potential for improved outcomes, yet molecular tests were used to screen travelers for COVID-19 with mixed success. To investigate why screening for COVID-19 was not more successful, and to quantify the limits of screening for other pathogens of concern, we developed a probabilistic model that incorporates within-host viral kinetics. We then evaluated the potential effectiveness of screening travelers with molecular tests for influenza A, SARS-CoV-1, SARS-CoV-2, and Ebola virus. Even under highly optimistic assumptions about behavior and test characteristics, we find screening effectiveness is always limited because the infections with the highest transmission potential are undetectable at the time of travel, an idea we term the fundamental limit of traveler screening. We also demonstrate how estimates of ascertainment are a misleading substitute for screening effectiveness because they overestimate reductions in transmission at the destination. Understanding these limitations can guide the deployment of future traveler screening programs and inform strategies to improve outbreak prevention and control.
His-MMDM: Multi-domain and Multi-omics Translation of Histopathological Images with Diffusion Models
Authors: Li Zhongxiao , Su Tianqi , Zhang Bin , Han Wenkai , Zhang Sibin , Sun Guiyin , Cong Yuwei , Chen Xin , Qi Jiping , Wang Yujie , Zhao Shiguang , Meng Hongxue , Liang Peng , Gao Xin 
Published: July 2024

AbstractGenerative AI (GenAI) has advanced computational pathology through various image translation models. These models synthesize histopathological images from existing ones, facilitating tasks such as color normalization and virtual staining. Current models, while effective, are mostly dedicated to specific source-target domain pairs and lack scalability for multi-domain translations. Here we introduce His-MMDM, a diffusion model-based framework enabling multi-domain and multi-omics histopathological image translation. His-MMDM is not only effective in performing existing tasks such as transforming cryosectioned images to FFPE ones and virtual immunohistochemical (IHC) staining but can also facilitate knowledge transfer between different tumor types and between primary and metastatic tumors. Additionally, it performs genomics-and/or transcriptomics-guided editing of histopathological images, illustrating the impact of driver mutations and oncogenic pathway alterations on tissue histopathology and educating pathologists to recognize them. These versatile capabilities position His-MMDM as a versatile tool in the GenAI toolkit for future pathologists.
Phosphoproteomics uncovers exercise intensity-specific signaling networks underlying high-intensity interval training in human skeletal muscle
Authors: Hoffman Nolan J. , Whitfield Jamie , Xiao Di , Radford Bridget E. , Suni Veronika , Blazev Ronnie , Yang Pengyi , Parker Benjamin L. , Hawley John A. 
Published: July 2024

SUMMARYIn response to exercise, protein kinases and signaling networks are rapidly engaged in skeletal muscle to maintain energy homeostasis. High-intensity interval training (HIIT) induces superior or similar health-promoting skeletal muscle and whole-body adaptations compared to prolonged, moderate-intensity continuous training (MICT). However, the exercise intensity-specific signaling pathways underlying HIIT versus MICT are unknown. Ten healthy male participants completed bouts of work- and duration-matched HIIT and MICT cycling in randomized crossover trials. Mass spectrometry-based phosphoproteomic analysis of human muscle biopsies mapped acute signaling responses to HIIT and MICT, identifying 14,931 phosphopeptides and 8,509 phosphosites. Bioinformatics uncovered >1,000 phosphosites significantly regulated by HIIT and/or MICT, including 92 and 348 respective HIIT-specific phosphosites after 5 and 10 min and >3,000 total phosphosites significantly correlated with plasma lactate. This first human muscle HIIT signaling network map has revealed rapid exercise intensity-specific regulation of kinases, substrates and pathways that may contribute to HIIT’s unique health-promoting effects.
Is aging acceleration mediating the association between hemoglobin glycation index and cardiovascular disease?
Authors: Liu Na , Li Yun , Li Mengying , Wang Yi , Li Bo , Lian Yongqiang , Fu Jianfang , Li Xiaomiao , Zhou Jie 
Published: July 2024

AbstractBackgroundThe potential factors beyond HbA1c that increase the risk of cardiovascular disease and age more quickly in people with diabetes are not yet clear. This study sought to determine the prospective associations between discrepancies in observed and predicted HbA1c levels, also known as the hemoglobin glycation index (HGI), and cardiovascular disease risk. Additionally, the interactions of HGI with accelerated aging in relation to cardiovascular disease risk were evaluated.MethodThis cross-sectional study included 9167 adults from the National Health and Nutrition Examination Survey 1999–2010. The HGI is used to assess individual blood glucose variability, and phenotypic age acceleration is employed to evaluate accelerated aging. Regression analysis, restricted cubic spline and mediation analysis explore the potential roles of phenotypic age acceleration in the relationship between HGI and CVD mortality.ResultsAmong the 9167 eligible participants (aged 20 years or older), 4390 (47.9%) were males, and the median (IQR) age was 48.0 (15.0) years; 4403 (48.0%) had prediabetes and diabetes, and 985 (10.7%) had cardiovascular disease. Restricted cubic splines showed that the association between HGI and CVD risk was nonlinear (p < 0.001). The greater the negative value of the HGI was, the greater the risk of CVD, and the association was independent of age, sex and HbA1c. Mediation analyses confirmed that phenotypic age acceleration acted as a mediator in the association between HGI and CVD risk (mediated effect: OR, 68.7%, 95% CI: 36.4%-153%,P=0.002).Conclusion and RelevanceThe HGI serves as a robust biomarker for assessing the acceleration of aging, regardless of HbA1c levels, and is associated with increased susceptibility to cardiovascular disease, particularly among individuals characterized by negative HGI.
Application of Principal Component Analysis to Heterogenous Fontan Registry Data Identifies Independent Contributing Factors to Decline
Authors: Ferrari Margaret R. , Schäfer Michal , Hunter Kendall S. , Di Maria Michael V. 
Published: July 2024

AbstractSingle ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that ultimately requires heart transplant. Our observational cohort study goal was to determine if principal component analysis (PCA) applied to data collected from a substantial Fontan cohort can predict functional decline (N=140). Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO2max), lymphatic biomarkers, and blood biomarkers were collected over 11 years at a single site; in that time, 16 events occurred that are considered here in a composite outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Our main findings suggest that the 6thPC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by blood serum biomarkers and superior vena cava flow, is a superior measure of proportional hazard compared to EF, and displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and lymphatic dysfunction (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Our findings support our hypothesis that a multifactorial model must be considered to improve prognosis in the Fontan population.
SSR42 is a Novel Regulator of Cytolytic Activity inStaphylococcus aureus
Authors: Jobson Mary-Elizabeth , Tomlinson Brooke R. , Mustor Emilee M. , Felton Emily A. , Weiss Andy , Caswell Clayton C. , Shaw Lindsey N. 
Published: July 2024

AbstractSSR42 is the longest noncoding RNA in theS. aureuscell and the second-most abundant transcript in the stationary phase transcriptome, second only to RNAIII. It is highly conserved across strains and exhibits pronounced stability in stationary phase, however the mechanism behind its regulatory role has yet to be fully elucidated. Herein, we used transcriptomic and proteomic approaches to probe the role of SSR42, revealing that it is a powerful, novel activator of the primary leukocidin LukAB. SSR42 is required for cytotoxicity towards, and escape from within, human neutrophils, and also mediates survival within human blood. We show that SSR42 wields this role via derepression by the peroxide repressor PerR in response to the presence of human neutrophils and governslukABinduction in this niche. Importantly, this regulation is driven by direct RNA-RNA interaction, as we show binding of the 5’ UTR of thelukABtranscript with the 3’ end of SSR42, which ultimately modulates transcript stability as well as translational activity. Finally, we demonstrate that this behavior is absolutely required for full virulence ofS. aureusin murine models of both pneumonia and sepsis. Collectively, we present SSR42 as a pleiotropic regulatory RNA that acts as a nexus between environmental sensing and the regulation of pathogenesis, responding to environmental stimuli and host immune factors to bolster cytotoxic behavior and facilitate infection inS. aureus.ImportanceS. aureusis a master pathogen due to its formidable collection of virulence factors. These are tightly controlled by a diverse group of regulators that titrate their abundance to adapt to unique infectious niches. The role of regulatory RNAs in stress adaptation and pathogenesis is becoming increasingly more relevant inS. aureus. In this study, we provide the most comprehensive global analysis to date of just such a factor, SSR42. Specifically, we uncover that SSR42 is required for mediating cytotoxicity - one of the pillars of infection - in response to phagocytosis by human neutrophils. We find that SSR42 is induced by components of the host immune system and facilitates downstream activation of cytotoxic factors via RNA-RNA interactions. This illustrates that SSR42 forms a pivotal link between sensing the external environment and mediating resistance to oxidative stress while promoting virulence, solidifying it as a major global regulator inS. aureus.
G-Quadruplex Structures in 16S rRNA Regions Correlate with Thermal Adaptation in Prokaryotes
Authors: Lyu Bo , Song Qisheng 
Published: July 2024

AbstractG-quadruplex (G4) structure is a nucleic acid secondary structure formed by sequences rich in guanine, playing essential roles in various biological processes such as gene regulation, maintenance of genome stability, and adaptation to environmental stresses. Although prokaryotes growing at high temperatures have higher GC contents, the pattern of G4 structure presence associated with GC content variation in thermal adaptation within genomes and ribosomal genes is rarely reported. In this study, we analyzed 681 bacterial genomes to investigate the role of G4 structures in thermal adaptation. Our findings revealed a strong positive correlation between G4 patterns in the region encoding 16S rRNA genes and optimal growth temperatures (Topt), whereas genomic GC content and overall G4 patterns did not show significant correlations with Topt. Evolutionary analysis showed significant differences in G4 stability betweenThermotoga(Topt≥ 80 °C) andPseudothermotoga(60°C ≤ Topt< 80°C) species, withThermotogaspecies exhibiting higher G4 stability, indicating stronger selective pressure for G4 stability under extreme conditions. Circular dichroism analysis showed that specific base mutations at key sites resulted in the absence of G4 thermal stability and structural integrity inThermotogacompared toPseudothermotoga. Collectively, this study suggests that the G4 structures in 16S rRNA encoding regions emerged as key indicators of thermal adaptation and contributes to our understanding of the molecular basis of thermal adaptation.
A novel monocyte-based biomarker of cardiovascular risk: comparison with QRISK3
Authors: Almarri Fatemah , Padayachee Soundrie , Kerr Alexander , Patel Ashish , Ferro Albert 
Published: July 2024

ABSTRACTAimsCirculating monocyte-platelet aggregates (MPA) and CD14+/CD16+monocytes are elevated in symptomatic patients with atherosclerotic cardiovascular disease. The aim of this study was to investigate their utility in prediction of early atherosclerosis in asymptomatic subjects, in comparison to a traditional cardiovascular risk calculator, QRISK3.MethodsAsymptomatic patients attending the hypertension clinic at Guy’s & St Thomas’ Hospitals, London, and healthy volunteer subjects recruited by advertisement, were enrolled (n = 39). Blood (30 mL) was processed for flow cytometry to measure CD14 and CD16 expression on monocytes, and CD14+CD42b+MPA. Using these measurements, a novel index termed the Monocyte Atherosclerotic Risk Score (MARS) was developed. All subjects also underwent carotid artery ultrasonic angiography.ResultsBoth QRISK3 and MARS correlated significantly with carotid intima-media thickness (cIMT); however, the correlation was much closer for MARS (r2= 0.8705, P < 0.0001) than for QRISK3 (r2= 0.3012, P = 0.0025). ROC analysis revealed MARS to be highly predictive both of cIMT-determined high cardiovascular risk (C-index = 0.9273, P = 0.0001) and presence of carotid plaque (C-index = 0.9385, P = 0.0022), whereas QRISK3 was not.ConclusionsMARS appears superior to QRISK3 in predicting both cIMT and carotid plaque disease. This may help to better identify asymptomatic individuals who would benefit from targeted imaging investigations and prophylactic therapies.LAY SUMMARYIn healthy people with no clinical evidence of cardiovascular disease, prediction of risk of atherosclerotic disease (including coronary heart disease and stroke) is notoriously unreliable; although traditional cardiovascular risk calculators work well at a population level, they are much less reliable in individuals.We have developed a blood based biomarker, which we term MARS, which is highly predictive of silent atherosclerosis: much more so than the traditional risk calculator QRISK3, currently in use in the UK.This opens the way to develop a blood test which can be applied clinically to more precisely identify healthy individuals who are at high cardiovascular risk, and who would therefore benefit from further imaging investigations and intensive treatment of cardiovascular risk factors.
Distinct immune signatures are a potent tool in the clinical management of cytokine-related syndrome during immune checkpoint therapy
Authors: Daoudlarian Douglas , Segot Amandine , Latifyan Sofiya , Bartolini Robin , Joo Victor , Mederos Nuria , Bouchaab Hasna , Demicheli Rita , Abdelhamid Karim , Ferahta Nabila , Doms Jacqueline , Stalder Grégoire , Noto Alessandra , Mencarelli Lucrezia , Mosimann Valérie , Berthold Dominik , Stravodimou Athina , Sartori Claudio , Shabafrouz Keyvan , Thompson John A , Wang Yinghong , Peters Solange , Pantaleo Giuseppe , Obeid Michel 
Published: July 2024

AbstractImmune-related cytokine release syndrome (irCRS) frequently occurs during immune checkpoint inhibitor (ICI) therapy. In the present study, we have attempted to identify biomarkers in oncology patients experiencing irCRS-like symptoms (n=35), including 9 patients with hemophagocytic lymphohistiocytosis (irHLH)-like manifestations (8 classified as Grade (G) 4 irCRS and 1 as G3 irCRS) and 8 with sepsis, differentiating between irCRS, irHLH and sepsis. Patients grouped in three clusters based on distinct cytokine profiles and survival outcomes. We identified 24 biomarkers that significantly discriminated between irHLH and irCRS G3 (P < 0.0455 to < 0.0027). Notably, HGF and ferritin demonstrated superior predictive values over the traditional HScore, with a positive predictive value (PPV) and negative predictive value (NPV) of 100%. Furthermore, CXCL9 not only distinguished between irHLH and irCRS G3, but was also a predictor of treatment intensification with tocilizumab (TCZ) with a PPV of 90% and a NPV of 100%. Other parameters, such as leukocyte count, neutrophils, ferritin, IL-6, IL-7, EGF, fibrinogen, and GM-CSF, were effective in discriminating sepsis from high-grade irCRS with a PPV of 75-80% and an NPV of 100%. In comparison to sepsis, the frequencies of CXCR5+ or CCR4+ CD8 memory, CD38+ ITM monocytes, and CD62L+ neutrophils were observed to be higher in high-Grade irCRS. Of note, TCZ treatment led to complete resolution of clinical symptoms in 12 patients with high-grade irCRS refractory to corticosteroids (CS). These findings demonstrate the power of unique immunologic biomarkers in determining the severity of irCRS, in predicting survival, and distinguishing between high-grade irCRS, irHLH and sepsis. Therefore, these distinct unique signatures are instrumental for the optimal development of personalized clinical and therapeutic management in patients experiencing irCRS patient.
Continuous nuclear envelope surveillance is required for DNA double-strand break repair
Authors: Medina-Suárez Sara , Machín Félix 
Published: July 2024

AbstractPrecise double-strand break (DSB) repair is paramount for genome stability. Homologous recombination (HR) is preferred to repair DSBs when a nearby sister chromatid ensures an error-free template. InSaccharomyces cerevisiae, this preference extends into anaphase and telophase (late mitosis; late-M), despite sister chromatids having been pulled apart. Previously, we identified the nuclear envelope (NE) protein Msc1 as important for late-M DSB repair. Here, we report that Msc1 faces the NE lumen, and its depletion leads to DSB-independent over-compartmentalization of the nucleus, which hampers approximation of sister loci after DSB. Depletion of Msc1 also leads to nuclear pore complex mislocation, a phenotype shared by the highly conserved NE healing complex ESCRT-III. Critically, we show that both Msc1 and ESCRT-III also ensure DSB repair in G2/M, and that there is synergism between Msc1 and the ESCRT-III subunit Snf7. These findings highlight the essential role of NE health in DSB repair.
Integrating technology acceptance model and value-based adoption model to determine consumers’ perception of value and intention to adopt AR in online shopping
Authors: Lai Zi Juan , Leong Mei Kei , Khoo Kim Leng , Sidhu Sarabjit Kaur 
Published: July 2024

PurposeThis study is among the first to integrate the technology acceptance model (TAM) and value-based adoption model (VAM) in the context of augmented reality (AR) shopping. It assesses how consumers' rational (TAM) and emotional (VAM) factors influence their intention to use AR in online shopping via perceived value and consumer engagement.Design/methodology/approachThis study uses a quantitative research approach and employs a standardized survey questionnaire distributed on social media platforms to recruit Gen Z members who are potential buyers or users of AR technology. SmartPLS 4.0 was used to test the responses of 204 respondents.FindingsThe results indicate that consumers who perceive a higher value of AR in shopping are inclined to use AR in their future shopping when AR shopping is easy to use, useful, personalized, innovative and provides a highly engaging experience. Interestingly, perceived sacrifice did not influence perceived value. This study confirms that integrating TAM and VAM is instrumental in capturing value, which in turn influences engagement and the intention to use AR in online shopping.Originality/valueThis study further extends the conceptualization of AR perceived value by combining rational components derived from TAM and VAM, thus leading to a sturdy and theoretically grounded framework. In addition, this study contributes to the literature on extended reality, namely AR shopping, and helps brand managers manage highly evolving AR experience for Gen Z.