bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing On-the-Fly Probability Enhanced Sampling for Complex RNA Systems: Sampling Free Energy Surfaces of an H-Type Pseudoknot
Authors: Malekzadeh Karim , Zerze Gül H. 
Published: October 2024

AbstractAll-atom molecular dynamics (MD) simulations offer crucial insights into biomolecular dynamics, but inherent time scale constraints often limit their effectiveness. Advanced sampling techniques help overcome these limitations, enabling predictions of deeply rugged folding free energy surfaces (FES) of RNAs at atomistic resolution. The Multithermal-Multiumbrella On-the-Fly Probability Enhanced Sampling (MM-OPES) method, which combines temperature and collective variables (CVs) to accelerate sampling, has shown promise and cost-effectiveness. However, the applications have so far been limited to simpler RNA systems, such as stem-loops. In this study, we optimized the MM-OPES method to explore the FES of an H-type RNA pseudoknot, a more complex fundamental RNA folding unit. Through systematic exploration of CV combinations and temperature ranges, we identified an optimal strategy for both sampling and analysis. Our findings demonstrate that treating the native-like contacts in two stems as independent CVs and using a temperature range of 300–480 K provides the most effective sampling, while projections onto native Watson-Crick-type hydrogen bond CVs yield the best resolution FES prediction. Additionally, our sampling scheme also revealed various folding/unfolding pathways. This study provides practical insights and detailed decision-making strategies for adopting the MM-OPES method, facilitating its application to complex RNA structures at atomistic resolution.TOC Graphic
5hmC-profiles in Puerto Rican Hispanic/Latino men with aggressive prostate cancer
Authors: Patel Manishkumar S , Almubarak Mousa , Matta Jaime , Ortiz-Sanchez Carmen , Encarnacion Jarline , Ruiz-Deya Gilberto , Dutil Julie , Dhillon Jasreman , Yamoah Kosj , Berglund Anders , Park Hyun , Kilari Deepak , Balagurunathan Yoganand , Wang Liang , Park Jong Y. 
Published: October 2024

AbstractPuerto Rican (PR) Hispanic/Latino (H/L) men are an understudied population that has the highest prostate cancer (PCa) specific mortality among other Hispanic populations. Little information is known about the higher mortality in PR H/L men. It is thought that epigenetic changes in key genes may play a critical role in aggressive tumors. We aimed to identify key 5-hydroxymethylcytosine (5hmC) changes in PR H/L men with aggressive PCa. We performed sequencing analysis using the 5hmC-enriched DNA from 22 prostate tumors and 24 adjacent normal FFPE samples. We identified 808 differentially methylated genes (DMGs) in tumors compared to adjacent normal tissues (FDR<0.05, log2FC>|0.4|). Pathway analysis of DMGs demonstrated that DNA repair pathway was most upregulated in tumors. Since 5hmC abundance positively correlates with gene expression levels, we further investigated 808 DMGs in TCGA PCa gene expression data. Further, we identified 59 DMGs (80.1%, FDR<0.05, ΔGE (gene expression) >|1|) with significant gene expression changes in the same direction. Additionally, we identified 111 aggressiveness-related DMGs, of which, two hypomethylated genes (CCDC122,NUDT15) and four hypermethylated genes (PVT1,RPL30,TRMT12,UBR5) were found to be altered at transcriptomic level in a concordant manner in PR H/L PCa patients (N=86). The aberrant 5hmC (N=55) and GE (N=497) changes in these six genes were also associated with progression-free survival in the mixed PCa population. In conclusion, our study identified 59 DMGs showing concordant epigenetic and transcriptomic changes in tumor tissues and 111 DMGs showing association with aggressive PCa among PR H/L men.
Biobank-scale exposome-wide risk factors in cardiometabolic disease: observational, predictive, and causal evidence
Authors: Tangirala Sivateja , Manrai Arjun K , Ioannidis John PA , Patel Chirag J 
Published: October 2024

AbstractCardiovascular disease and diabetes are intricately related and influenced by factors within the “exposome”. Distinguishing between correlational and causal risk associations is challenging, especially at exposome scale. Here, we triangulate observational Exposure-Wide Association Study (ExWAS) evidence with “randomized” evidence for the exposome using mendelian randomization (MR) for almost 500 exposures. First, theExWASidentified 144 significant factors for coronary artery disease (CAD) and 237 for type 2 diabetes (T2D), with 120 shared between both. These factors had modest predictive ability (variance explained) for both phenotypes. However, genetic-based causality was deduced for only 14 factors in CAD and 16 in T2D, with seven implicated in both. Additionally, we found strong concordance of MR-validated findings between prevalent and incident disease associations (85.7% [12/14] for CAD and 87.5% [14/16] for T2D). Most correlational findings pertain to lifestyle factors (particularly diet), but social educational factors are more prominently highlighted among those with causal support.
CTRhythm: Accurate Atrial Fibrillation Detection from Single-Lead ECG by Convolutional Neural Network and Transformer Integration
Authors: Liang Zhanyu , Yang Chen , Yu Zhengyang , Fu Yinmingren , Ren Bozhen , Lin Maohuan , Li Qingjiao , Liu Xuemei , Chen Yangxin , Xia Li C. 
Published: October 2024

AbstractAtrial Fibrillation (AF) is a common supraventricular arrhythmia that affects about 30 million people globally. Electrocardiogram (ECG) analysis is the primary diagnostic approach. The widespread adoption of wearable devices monitoring heart rhythm prompted the development of AF detection models for single-lead ECGs, benefitting real-time early diagnosis. Current state-of-the-art methods for AF detection are convolutional neural network (CNN) and convolutional recurrent neural network (CRNN) based models, which only focus on capturing local patterns despite heart rhythms exhibiting rich long-range dependencies. To address this limitation, we propose a novel method for single-lead ECG rhythm classification, termed CNN-Transformer Rhythm Classifier (CTRhythm), which integrates CNN with a Transformer encoder to capture local and global patterns effectively. CTRhythm achieved an overall F1 score of 0.831, outperforming the baseline deep learning models on the golden standard CINC2017 dataset. Moreover, pre-training with additional data improved the overall F1 score to 0.840. In two external validation datasets, CTRhythm showed its strong generalization capabilities. CTRhythm is freely available athttps://github.com/labxscut/CTRhythm.
Malaria prevention in the age of climate change: A community survey in rural Senegal
Authors: Sherman Andrew C.L. , Matthews Jesse D. , Aligne C. Andrew 
Published: October 2024

AbstractBackgroundMalaria results in over 600,000 deaths per year, with 95 percent of all cases occurring in sub-Saharan Africa. Despite significant steady reductions from 2000 to 2015, there has been a recent resurgence. The estimated 2025 Africa death rate was recalculated to be 51.8 people per 100,000, whereas the previous estimate was 15.9. A potential explanation for this very significant setback is that increasing temperatures associated with global warming have made it more difficult to use insecticide treated mosquito nets. This study evaluated a rural west African population to determine barriers to mosquito net use, including heat and outdoor sleeping.MethodsThis study used a social ecological framework used by the Peace Corps to determine this community’s barriers to malaria prevention. We practiced community-based participatory research by developing and implementing a survey in rural southeast Senegal. Local village health workers were trained specifically to implement this survey. Observations of the mosquito nets and sleeping spaces were performed by surveyors. 164 households in 20 villages were surveyed from October to November of 2012.Results164 of 164 selected households were surveyed, giving a 100% response rate, representing 21% of this local population. For the 1806 family members, respondents assessed a total need of 1565 nets, implying that each individual in this area needs 0.86 nets (95% CI: 0.77-0.95). The main reasons for not using an available net were heat and fragility of the nets. This population had very positive attitudes regarding mosquito nets and appreciated the work of local malaria educators.ConclusionsThe estimated need of 0.86 nets per person is 54% higher than the World Health Organization recommendation. Heat was found to be a major barrier in using a mosquito net, causing more people to sleep on outdoor structures. This study’s findings suggest the ratio of nets to people may need to be adjusted for the substantial increase in outdoor sleeping. Head of household responses in this population were found to have no systemic bias and would be an accurate way to assess a family’s need of nets. Deploying more malaria educators to this area would be appreciated and beneficial.
Artificial neural networks to predict virological and immunological success in HIV patients under antiretroviral therapy from a nationwide cohort in Colombia, using the SISCAC database
Authors: Buitrago-Gutierrez Alberto , Porras-Ramirez Alexandra 
Published: October 2024

AbstractObjectiveThis study aimed to develop predictive models both for viral suppression and immunological reconstitution using a standard set of reported variables in a nationwide database system (SISCAC) from a cohort of patients living with HIV in Colombia.Materials and MethodsWe included 2.182 patients with no missing data related to the outcomes of interest, during a 12 month follow up period. We randomly assigned a 0,7 proportion of this cohort to de training dataset for 2 different predictive models (logistic regression, artificial neural networks). The AUC/ROC results were compared with those obtained through the construction of artificial neural networks with the specified parameters.ResultsFrom a cohort of 2182 patients, 85,79% were male and at HIV diagnosis, the mean value of the CD4 count was 342 x mm3. The logistic regression models obtained AUC/ROC accuracy for the outcomes “suppressed viral load” 0,7, “undetectable viral load” of 0,66 and “immunological reconstitution” 0,83; whereas the artificial neural network perceptron multilayer obtained AUC/ROC of 0,77, 0.69 and 0,87 for the same outcomes.ConclusionsThe selection of specific variables from a nationwide database in Colombia with quality control purposes allowed us to generate predictive models with an initial evaluation of performance regarding three predefined outcomes for virological and immunological success.
Neighborhood Influences on the Geography of Type 2 Diabetes in Malaysia: A Geospatial Modelling Study
Authors: Ganasegeran Kurubaran , Abdul Manaf Mohd Rizal , Safian Nazarudin , Waller Lance A. , Mustapha Feisul Idzwan , Abdul Maulud Khairul Nizam , Mohd Rizal Muhammad Faid 
Published: October 2024

AbstractType 2 diabetes (T2D) often exhibits long-standing disparities across populations. Spatial regression models can identify areas of epidemiological conformity and transitions between local neighborhoods to inform timely, localized public health interventions. We identified areal-level distributions of T2D rates across Malaysia and synthesized prediction models to estimate local effects and interactions of different neighborhood covariates affecting local T2D burden. We obtained aggregated counts of national level T2D cases data by administrative-districts between 2016-2020 and computed district-wise crude rates to correlate with district-level neighborhood demographic, socio-economic, safety, fitness, access to built-environments, and urban growth indicators from various national sources and census data. We applied simultaneous spatial autoregressive (SAR) models coupled with two-way interaction analyses to account for spatial autocorrelation and estimate risk factors for district-level T2D rates in Malaysia. The variation in spatial lag estimates of T2D rates by districts was influenced by the proportion of households living below 50% of the median income (β = 0.009,p= 0.002) and national poverty line (β = - 0.012,p= 0.001), income inequalities (β = - 2.005,p= 0.004), CCTV coverage per 1000 population (β = 0.070,p= 0.023), average property crime index per 1000 population (β = 0.014,p= 0.033), access to bowling centers (β = - 0.003,p= 0.019), and parks (β = 0.007,p= 0.001). Areal-level district-wise crude T2D rate estimates were influenced by neighborhood socio-economic vulnerabilities, neighborhood safety, and neighborhood access to fitness facilities, after accounting for residual spatial correlation via SAR models.
Fructose Activates a Stress Response Shared by Methylglyoxal and Hydrogen Peroxide inStreptococcus mutans
Authors: Walker Alejandro R. , Pham Danniel N. , Noeparvar Payam , Peterson Alexandra M. , Lipp Marissa K. , Lemos José A. , Zeng Lin 
Published: October 2024

AbstractFructose catabolism byStreptococcus mutansis initiated by three PTS transporters yielding either fructose-1-phoshate (F-1-P) or fructose-6-phosphate (F-6-P). Deletion of one such F-1-P-generating PTS,fruI, has been shown to reduce the cariogenicity ofS. mutansin rats fed a high-sucrose diet. Moreover, a recent study linked fructose metabolism inS. mutansto a reactive electrophile species (RES) methylglyoxal. Here, we conducted a comparative transcriptomic analysis of exponentially grownS. mutansshocked with 50 mM fructose, 50 mM glucose, 5 mM methylglyoxal, or 0.5 mM hydrogen peroxide (H2O2). The results revealed a striking overlap between the fructose and methylglyoxal transcriptomes, totaling 176 genes, 61 of which were also shared with the H2O2transcriptome. This core of 61 genes encompassed many of the same pathways affected by exposure to low pH or zinc intoxication. Consistent with these findings, fructose negatively impacted metal homeostasis of a mutant deficient in zinc expulsion and the growth of a mutant of the major oxidative stress regulator SpxA1. We further demonstrated the induction of the superoxide dismutase (sodA) and thefruRKIoperon by different levels of fructose. Finally, fructose metabolism lowered culture pH at a faster pace, allowed better survival under acidic and nutrient-depleted conditions, and enhanced the competitiveness ofS. mutansagainstStreptococcus sanguinis, although a moderated level of F-1-P might further boost some of these benefits. In conclusion, fructose metabolism is integrated into the stress core ofS. mutansand regulates critical functions required for survival in both the oral cavity and during systemic infections.ImportanceFructose is a common monosaccharide in the biosphere, yet its overconsumption has been linked to various health problems in humans including insulin resistance, obesity, diabetes, and non-alcoholic liver diseases. These effects are in large part attributed to the unique biochemical characteristics and metabolic responses associated with the degradation of fructose. Yet, an understanding of the effects of fructose on the physiology of bacteria and its implications to the human microbiome is severely lacking. Here we performed a series of analyses on the gene regulation of a dental pathogenStreptococcus mutansby exposing it to fructose and other important stress agents. Further supported by growth, persistence, and competition assays, our findings revealed the ability of fructose to activate a set of cellular functions that may prove critical to the ability of the bacterium to persist and cause diseases both within and without of the oral cavity.
Innate antiviral systems are major defensome components that drive prophage distribution inAcinetobacter baumannii
Authors: Moreno-Rodríguez Antonio , Rubio Alejandro , Garzón Andrés , Smani Younes , Pérez-Pulido Antonio J. 
Published: October 2024

AbstractPhages are guilty of killing daily almost half of bacterial cells, while bacteria have developed defense mechanisms that number in the dozens. Individual defense systems are gained and lost by genomes of the same species, depending on their fitness advantage. Thus, some genomes have a certain combination of defense systems, while other genomes act as a reservoir for the rest of the systems, thus constituting the so-called pan-immune system of the species. Here we have analyzed thousands of genomes of the bacteriumAcinetobacter baumannii, an opportunistic pathogen of humans of great clinical concern, and we have found 81 different defense systems heterogeneously distributed. By analyzing how these systems combine, we have found that more than half of the genomes lack the universal DNA-methylating restriction-modification systems (R-M) and harbor an alternative innate SspBCDE system that performs a DNA phosphorothioate modification. In addition, the adaptive CRISPR-Cas systems could act synergistically to the R-M systems, based on their frequency of co-appearance. The presence of one or the other innate system could modulate the evolution of the genomes of this species, causing them to present a different profile of phages integrated into the bacterial genome. We have also observed that the presence of many defense systems is associated with the presence of a higher number of prophages, which could be due to the fact that the prophage carries the system, or that the bacterium would not need these systems in environments where the phage is absent.
IGF2 mediates Hippo signaling to control liver size
Authors: Zhong Zhenxing , Jin Ruxin , Zhong Yiting , Zhang Li , Chen Deqian , Jiao Zhihan , Zhou Fanhui , Zhu Rui , Wu Jian , Dong Rui , Dong Kuiran , Lan Fei , Wang Yu , Guan Kun-Liang , Yu Fa-Xing 
Published: October 2024

ABSTRACTThe Hippo pathway is a central mechanism in organ size control, but the mediator for its function remains elusive. Here, we show that the expression of insulin-like growth factor II (IGF2) is directly induced by YAP/TAZ transcription cofactors of the Hippo pathway in a developmental stage- and cell type-specific manner. In mouse livers,Igf2expression is sustained by YAP/TAZ in hepatoblasts and immature hepatocytes at fetal and neonatal stages, coupling with rapid cell proliferation and liver size expansion, whereas turned off in matured hepatocytes following YAP/TAZ inactivation to prevent liver overgrowth. In contrast, YAP/TAZ fails to regulateIgf2expression in cholangiocytes and diverse liver mesenchymal cells where epigenetic barriers, including DNA and histone methylation, are implanted nearIgf2promoters. Furthermore, IGF2 activates IGF1R signaling and promotes normal and neoplastic liver growth, while the inactivation of IGF2 or IGF1R effectively blocks YAP/TAZ-induced hepatomegaly and hepatoblastoma. In conclusion, our findings reveal that IGF2 is abona fidemediator of the Hippo pathway, indicating a fundamental role of the Hippo-IGF2-IGF1R signaling axis in organ size regulation and malignancies.
Constraining gravitational-wave backgrounds from conversions into photons in the Galactic magnetic field
Authors: Lella Alessandro , Calore Francesca , Carenza Pierluca , Mirizzi Alessandro 
Published: October 2024

High-frequency gravitational waves (f≳1  MHz) may provide a unique signature for the existence of exotic physics. The lack of current and future gravitational-wave experiments sensitive at those frequencies leads to the need of employing different indirect techniques. Notably, one of the most promising ones is constituted by graviton-photon conversions in magnetic fields. In this work, we focus on conversions of a gravitational-wave background into photons inside the Milky Way magnetic field, taking into account the state-of-the-art models for both regular and turbulent components. We discuss how graviton-to-photon conversions may lead to imprints in the cosmic photon background spectrum in the range of frequencies f∼109–1026  Hz, where the observed photon flux is widely explained by astrophysics emission models. Hence, the absence of any significant evidence for a diffuse photon flux induced by graviton-photon conversions allows us to set stringent constraints on the gravitational-wave strain hc, strengthening current astrophysical bounds by ∼1–2 orders of magnitude in the whole range of frequencies considered.

Published by the American Physical Society
2024
Consumers’ attitudes towards healthy eating: a qualitative comparison between older and younger Chinese consumers
Authors: Dong Jingyu , Clark Beth , Li Wenjing , Jin Shan , Frewer Lynn J 
Published: October 2024

PurposeUnhealthy diets are associated with an increased risk of non-communicable diseases and present a significant public health challenge. When developing effective interventions and policies, consideration must be given to the unique social culture in which food choice is embedded. Health vulnerabilities to poor nutrition exist throughout life but may be influenced by socio-cultural factors such as age. This study aimed to assess the attitudes of older or younger Chinese consumers towards healthy eating and explore the factors influencing their food choices.Design/methodology/approachSemi-structured interviews were conducted in Wuhan, China, with 20 consumers aged 18–25 (Group A) and 20 consumers aged 65 and over (Group B).FindingsThematic analysis revealed that the two groups had positive attitudes towards healthy eating, although Group A participants were more knowledgeable. Time pressure, food prices and social networks differentially influence healthy eating practices across age groups.Originality/valueGiven China’s economic and cultural context, healthy eating interventions should consider the individual characteristics and food preferences of the different age groups. This approach can optimize targeted healthy eating interventions, and media communications related to healthy eating.
Consumers’ perception and willingness to pay for hydroponic tomatoes: the effects of sustainability and quality attributes
Authors: D'Amico Antonia , De Boni Annalisa , Ottomano Palmisano Giovanni , Morea Enrica , Acciani Claudio , Roma Rocco 
Published: October 2024

PurposeThe agricultural sector is facing pressure due to concerns about its impact on the environment. Farmers must adapt to ensure high-quality, sustainable production. This requires efficient techniques such as soilless farming. The development of agricultural innovations depends on social acceptance; thus, it is crucial to identify the factors that influence consumers' purchasing decisions. The aim of this paper is to analyse consumers' perceptions of hydroponic cultivation techniques and their willingness to pay (WTP) a premium price for hydroponic tomatoes certified as “nickel-free” and “zero-residue”.Design/methodology/approachThe survey was conducted in Italy using tomatoes as a case study. Data were collected through an online questionnaire from a convenience sample of 292 respondents and were analysed using statistical analysis and a multiple linear regression model.FindingsThe results showed that WTP was influenced by frequency of purchase, familiarity with soilless technology, environmental sustainability, income and education. Consumers place a high value on the sustainability of the hydroponic production process and their perception of increased safety positively influences WTP. It is therefore recommended that marketing strategies focus on the environmental sustainability and safety of hydroponic products. In addition, it may be beneficial to implement a certification system specific to hydroponic cultivation, in addition to the existing “nickel-free” and “zero-residue” certifications.Originality/valueThis study introduces several novel elements: it is the first to assess the Italian consumers’ perceptions and WTP for a hydroponic product. Secondly, it assesses WTP in relation to several aspects of increasing relevance related to health claims, namely “nickel-free” and “zero-residue”.