bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Profiling of a Triple-negative Breast Cancer Cohort in India for EGFR and AR expression analyzed for patient outcomes showed a distinct subset of cellular co-expression
Authors: Vaid Pooja , Puntambekar Anirudha , Kanse Pranali , Kadu Shweta , Agrawal Piyush , Khatpe Aditi , Banale Rituja , Reddy Ruhi , Kelkar Devaki A. , Hannenhalli Sridhar , Shashidhara L S , Koppiker Chaitanyanand , Kulkarni Madhura
Published: October 2024

TNBC is the most aggressive breast cancer subtype, with a higher recurrence rate. TNBC proportion within breast cancer incidence in the Indian population is 22-30%. Despite the high incidence rate, the heterogeneity within TNBC subtype in Indian cohorts is not studied at scale.

Here, leveraging an Indian cohort of 93 TNBC patients, we evaluated the basal and LAR subtypes in terms of the expression of known markers such as EGFR and AR and further assessed the association of marker gene expression with patient outcome and treatment response.

In our cohort, 65% of the patients were EGFR-positive, 38% had positive AR expression, where both the subsets showed shorter disease-free survival outcomes. Additionally, 25% of the cohort showed AR and EGFR co-expression. Upon closer observation, using IHC and duplex staining, we noted that 15% of the tumors, in fact, had double-positive cancer cells, i.e., cellular co-expression of AR and EGFR. Patients with double-positive cells had poorer disease-free survival compared to the ones with the tissue-level co-expression of EGFR and AR but without cellular co-expression. The presence of EGFR+AR+ double-positive cells was further validated in publicly available single-cell data sets for TNBC patients from other ethnic backgrounds, albeit to a lesser extent than what was observed in our Indian cohort. Overall, our results highlight the heterogeneous nature of Indian TNBC tumors and provide further insight into ethnic variation in TNBC presentation that can be further exploited for precision and personalized targeted therapy.
Effect of the Choosing Wisely Canada campaign on prescription of nonsteroidal anti-inflammatory drugs in people with hypertension, heart failure and chronic kidney disease in Canada
Authors: Hategeka Celestin , Cheng Lucy , Worthington Heather C , Laba Tracey-Lea , Law Michael R
Published: October 2024

The Choosing Wisely Canada (CWC) campaign focuses on helping physicians and patients engage in conversations about unnecessary tests and treatments. In 2014, a CWC recommendation advised against prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) in individuals with hypertension, heart failure or chronic kidney disease (CKD). We evaluated the impact of this recommendation on prescription of NSAIDs in British Columbia (BC), Canada. We identified all persons continuously registered with BC’s Medical Service Plan at any point between October 1, 2011 and December 31, 2017 with hypertension, heart failure or CKD. Using prescription claims data and an interrupted time series analysis, we estimated the quarterly number of people initiating NSAIDs and the proportion of days covered (PDC). We also conducted sub-group analyses to study the impact of the recommendation by patients’ demographics (sex and age). We analyzed 1,479,704 NSAID claims from 903,732 patients with a diagnosis of hypertension, heart failure and/or CKD. Overall, we found no statistically significant change either immediately or over time in initiation and PDC of NSAIDs. However, we did observe a decrease in both initiation and PDC of NSAIDs over time among male patients and patients aged ≤65 years. We found that the CWC recommendation had a mixed impact, with initiation and PDC of NSAIDs significantly declining only among male and younger patients.

Highlights

Reducing low-value care can help to counter increasing healthcare spending.

CWC can contribute to reducing low-value care, however, evidence on its effectiveness remains elusive.

CWC led to NSAIDs prescription decline for patients ≤65 years and male patients.

Overall, NSAID prescribing has been declining over time irrespective of CWC.
Enhanced Prediction of Seafloor Ecological State Using 16S Nanopore Sequencing
Authors: Philip Melcy , Nilsen Tonje , Majaneva Sanna , Pettersen Ragnhild , Stokkan Morten , Ray Jessica Louise , Keeley Nigel , Rudi Knut , Snipen Lars-Gustav
Published: October 2024

Anthropogenic stress on benthic habitats, particularly from aquaculture, calls for accurate and efficient monitoring of the macrofauna ecological state. Recent advancements in Oxford Nanopore Technology (ONT) together with environmental DNA offers cost-effective and rapid, on-site monitoring of such ecosystems. Previous studies have demonstrated that Nanopore sequencing provides sufficient precision for predicting ecological state, despite reported challenges with sequencing accuracy. In this study, we aim to predict the seafloor ecological state with both Illumina and Nanopore 16S rRNA gene sequencing data and using a combination of machine learning and feature selection. We analyzed 88 seafloor samples from aquaculture sites located on a north-south gradient along the Norwegian coast. Both sequencing methods were evaluated in combination with various bioinformatic approaches in the context of predicting the normalized EQR index (nEQR, standard ecological index based on macroinvertebrate counting) as a metric of seafloor ecosystem status. Our results show that the predictive performance of Illumina and Nanopore sequencing platforms are comparable, establishing Nanopore as a feasible alternative to illumina sequencing. By employing a stabilized LASSO regression, the feature set (potential taxa) was efficiently optimized from thousands to 40-60 OTUs. The feature selection reduced prediction errors to less than half of what was obtained through full feature modeling. This feature set demonstrated strong predictive accuracy across both sequencing technologies, with a high correlation between observed and predicted nEQR values. The Pearson correlation coefficient of 0.98 for Illumina and 0.95 (mean prediction error: ±0.04) for Nanopore data (mean prediction error: ±0.06). This study demonstrates that continual improvements in Nanopore sequencing accuracy, in combination with optimized feature selection on a broader set of samples, provides a precise and cost-effective monitoring method for marine benthic environments.
Seeing isn’t believing? Mixed effects of a perspective-getting intervention to improve mentoring relationships for science doctoral students
Authors: Tuma Trevor T. , Fedesco Heather N. , Rosenzweig Emily Q. , Chen Xiao-Yin , Dolan Erin L.
Published: October 2024

Science doctoral students can experience negative interactions with faculty mentors and internalize these experiences, potentially leading to self-blame and undermining their research self-efficacy. Helping students perceive these interactions adaptively may protect their research self-efficacy and maintain functional mentoring relationships. We conducted a pre-registered, longitudinal field experiment of a novel perspective-getting intervention combined with attribution retraining to help students avoid self-blame and preserve research self-efficacy. Science doctoral students (n= 155) were randomly assigned to read about mentor perspectives on negative interactions (i.e., Perspective-getting Condition) or about mentoring with no mentor perspective (i.e., control condition). Contrary to our hypotheses, we found no main effects of the intervention on students’ self-blame or research self-efficacy. However, for students with lower pre-intervention mentorship relationship satisfaction, the intervention preserved research self-efficacy six months later. This study provides evidence that perspective getting may be protective for students who are most in need of relationship intervention.

Educational Relevance and Implications Statement

Effective mentoring relationships are fundamental for promoting the success of doctoral students in science, yet not all mentoring relationships are high quality. This study assessed the effectiveness of a brief perspective-getting intervention (where students are given the perspective of what it is like to be a research mentor) that aimed to protect science doctoral students from blaming themselves for negative interactions with faculty mentors and maintain their research self-efficacy. Results showed that on average across all students, the intervention did not affect students’ self-blame for negative interactions or their research self-efficacy. However, the intervention did help students with less satisfying mentoring relationships maintain their self-efficacy. Thus, perspective-getting shows some promise for protecting science doctoral students from harm that can be caused by negative interactions with faculty mentors.
Developing a Multiscale Neural Connectivity Knowledgebase of the Autonomic Nervous System
Authors: Imam Fahim T. , Gillespie Thomas H. , Ziogas Ilias , Surles-Zeigler Monique C. , Tappan Susan , Ozyurt Burak I. , Boline Jyl , de Bono Bernard , Grethe Jeffrey S. , Martone Maryann E.
Published: October 2024

The Stimulating Peripheral Activity to Relieve Conditions (SPARC) program is a U.S. National Institutes of Health (NIH) funded effort to enhance our understanding of the neural circuitry responsible for visceral control. SPARC’s mission is to identify, extract, and compile our overall existing knowledge and understanding of the autonomic nervous system (ANS) connectivity between the central nervous system and end organs. A major goal of SPARC is to use this knowledge to promote the development of the next generation of neuromodulation devices and bioelectronic medicine for nervous system diseases. As part of the SPARC program, we have been developing SCKAN, a dynamic knowledge base of ANS connectivity that contains information about the origins, terminations, and routing of ANS projections. The distillation of SPARC’s connectivity knowledge into this knowledge base involves a rigorous curation process to capture connectivity information provided by experts, published literature, textbooks, and SPARC scientific data. SCKAN is used to automatically generate anatomical and functional connectivity maps on the SPARC portal.

In this article, we present the design and functionality of SCKAN, including the detailed knowledge engineering process developed to populate the resource with high quality and accurate data. We discuss the process from both the perspective of SCKAN’s ontological representation as well as its practical applications in developing information systems. We share our techniques, strategies, tools and insights for developing a practical knowledgebase of ANS connectivity that supports continual enhancement.
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

All-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

Puerto 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

Cardiovascular 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

Atrial 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

Background

Malaria 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.

Methods

This 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.

Results

164 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.

Conclusions

The 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

Objective

This 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 Methods

We 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.

Results

From 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.

Conclusions

The 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

Type 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

Fructose 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.

Importance

Fructose 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

Phages 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.
Deep learning-derived age of hippocampus-centred regions is influenced by APOE genotype and modifiable risk factors
Authors: Dong Chao , Pan Yuangang , Thalamuthu Anbupalam , Jiang Jiyang , Du Jing , Mather Karen , Sachdev Perminder S , Wen Wei
Published: October 2024

Brain age has been widely investigated by using the whole brain image. However, the age of some specific brain regions, such as those related to the hippocampus, remains underexplored. This study developed age prediction models for left and right hippocampus-centred regions of interest (hippocampus ROI) using three-dimensional convolutional neural networks (3D-CNN) based on MRI scans from 31,370 healthy participants in the UK Biobank. The hippocampus ROI age (HA) gap was calculated by subtracting chronological age from predicted HA. Additionally, the longitudinal change rate of the HA gap was estimated in 3,893 participants with imaging data at two time points over an average follow-up of 2.63 years. The models achieved state-of-the-art performance (mean absolute error (MAE): 2.47 to 2.84 years). Cross-sectional analysis revealed that APOE ε4 homozygotes had a greater HA gap compared to APOE ε4 non-carriers. Participants with hypertension, diabetes, heavy alcohol consumption, or smoking also exhibited larger HA gap. Transfer learning applied to an independent dataset confirmed similar trends in some variables, though findings were not statistically significant. Interestingly, longitudinal analysis showed that APOE ε4 homozygotes had a higher annual change rate in the left HA gap compared to APOE ε2 homozygotes. Occlusion analysis saliency maps indicated that regions around the hippocampus, including the thalamus, pallidum, nearby cerebral cortex, and white matter, significantly contributed to the age prediction. The left HA gap emerges as a potential biomarker linked to the APOE genotype and an indicator of health.
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

The 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.
An optimized protocol for quality control of gene therapy vectors using nanopore direct RNA sequencing
Authors: Zeglinski Kathleen , Montellese Christian , Ritchie Matthew E. , Alhamdoosh Monther , Vonarburg Cédric , Bowden Rory , Jordi Monika , Gouil Quentin , Aeschimann Florian , Hsu Arthur
Published: October 2024

Despite recent advances made toward improving the efficacy of lentiviral gene therapies, a sizeable proportion of produced vector contains an incomplete and thus potentially nonfunctional RNA genome. This can undermine gene delivery by the lentivirus as well as increase manufacturing costs and must be improved to facilitate the widespread clinical implementation of lentiviral gene therapies. Here, we compare three long-read sequencing technologies for their ability to detect issues in vector design and determine nanopore direct RNA sequencing to be the most powerful. We show how this approach identifies and quantifies incomplete RNA caused by cryptic splicing and polyadenylation sites, including a potential cryptic polyadenylation site in the widely used Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE). Using artificial polyadenylation of the lentiviral RNA, we also identify multiple hairpin-associated truncations in the analyzed lentiviral vectors (LVs), which account for most of the detected RNA fragments. Finally, we show that these insights can be used for the optimization of LV design. In summary, nanopore direct RNA sequencing is a powerful tool for the quality control and optimization of LVs, which may help to improve lentivirus manufacturing and thus the development of higher quality lentiviral gene therapies.
Refining radiative decay studies in singly heavy baryons
Authors: Peng Yu-Xin , Luo Si-Qiang , Liu Xiang
Published: October 2024

In this work, we systematically study the radiative decays of singly heavy baryons, a crucial aspect of their spectroscopic behavior. To enhance the accuracy of our calculations, we utilize numerical spatial wave functions for the singly heavy baryons obtained through the Gaussian expansion method, which also yields their mass spectrum. As hadron spectroscopy enters an era of high precision, we believe our study of the radiative decays of singly heavy baryons will provide valuable insights for further exploration of these particles.

Published by the American Physical Society
2024
Tetraquarks from intrinsic heavy quarks
Authors: Vogt R.
Published: October 2024

A number of new tetraquark candidate states containing from one to four charm or anticharm quarks have been observed recently. Many of these new states have been discovered at the LHC. The production of these states via intrinsic charm in the proton is investigated. The tetraquark masses obtained in this approach, while dependent on the internal transverse momenta of the partons in the state, are shown to agree well with the measured masses. These calculations can provide some insight into the nature of the tetraquark candidates, whether as a bound meson pair or as a looser configuration of four individual partons. The kinematic distributions of these states as a function of rapidity and transverse momentum are also studied. The possible cross sections for these states are finally considered, with a comparison to the X(3872) pT distributions from p+p collisions at s=13  TeV.

Published by the American Physical Society
2024
Dynamics of
U(1)
gauged
Q
-balls in three spatial dimensions
Authors: Kinach Michael P. , Choptuik Matthew W.
Published: October 2024

We investigate the dynamics of U(1) gauged Q-balls using fully three-dimensional numerical simulations. We consider two different scenarios: first, the classical stability of gauged Q-balls with respect to generic three-dimensional perturbations, and second, the behavior of gauged Q-balls during head-on and off-axis collisions at relativistic velocities. With regard to stability, we find that there exist gauged Q-ball configurations which are classically stable in both logarithmic and polynomial scalar field models. With regard to relativistic collisions, we find that the dynamics can depend on many different parameters such as the collision velocity, relative phase, relative charge, and impact parameter of the colliding Q-balls.

Published by the American Physical Society
2024
Complete study of RG evolution induced leptogenesis in flavor symmetry scenarios
Authors: Zhao Zhen-hua , Wu Xiang-Yi , Zhang Jing
Published: October 2024

In the literature, motivated by the observed peculiar neutrino mixing pattern and a preliminary experimental hint for maximal Dirac CP phase (i.e., δ∼3π/2), a lot of flavor and CP symmetries have been proposed to help us understand and explain these experimental results. However, for some flavor-symmetry scenarios (see section motivations of our study), the leptogenesis mechanism is prohibited from working as usual. To tackle this problem, in this paper we have made an exhaustive study of the possibility that the renormalization group evolution effect may induce a successful leptogenesis for these particular scenarios. Our study provides complementarities to the previous related studies in Xing and Zhang, []; Xing and Zhang, []; and Cooper , [] (see section complementarities of our study to previous related studies).

Published by the American Physical Society
2024
Application of partial wave analysis in multiphoton pair production
Authors: Fan Hong-Hao , Hu Li-Na , Tang Suo , Li Zi-Liang , Xie Bai-Song
Published: October 2024

Electron-positron pair production is investigated in the multiphoton regime under polarized fields. Partial wave analysis can be applied to reveal the momentum spectral structure and identify the positions of valleys/peaks of the multiphoton rings by combining with CP conservation. Moreover, considering the spin states of created pairs in partial wave analysis, the particle orbital angular momentum associated with the valleys/peaks can also be identified from multiphoton rings. It is found that the approximate analytical treatments for angular distribution by using partial wave analysis are consistent with those of the numerical calculation using the Dirac-Heisenberg-Wigner formalism. The results are helpful for understanding the angular momentum information in momentum spectra, and they also have an implication for revealing the vortex structure near the valleys where the amplitude nearly vanishes.

Published by the American Physical Society
2024
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
Quantized Integrated Shift Effect in Multigap Topological Phases
Authors: Jankowski Wojciech J. , Slager Robert-Jan
Published: October 2024

We show that certain three-dimensional multigap topological insulators can host quantized integrated shift photoconductivities due to bulk invariants that are defined under reality conditions imposed by additional symmetries. We recast the quantization in terms of the integrated torsion tensor and the non-Abelian Berry connection constituting Chern-Simons forms. Physically, we recognize that the topological quantization emerges purely from virtual transitions contributing to the optical response. Our findings provide another quantized electromagnetic dc response due to the nontrivial band topology, beyond the quantum anomalous Hall effect of Chern insulators and quantized circular photogalvanic effect found in Weyl semimetals.

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

Purpose

Unhealthy 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/approach

Semi-structured interviews were conducted in Wuhan, China, with 20 consumers aged 18–25 (Group A) and 20 consumers aged 65 and over (Group B).

Findings

Thematic 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/value

Given 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

Purpose

The 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/approach

The 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.

Findings

The 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/value

This 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”.
Navigating the moral maze: a literature review of ethical values in business process management
Authors: Kern Christopher Julian , Poss Leo , Kroenung Julia , Schönig Stefan
Published: October 2024

Purpose

Business process management (BPM), as a pillar of information systems (IS) research, has become more complex with the advent of new technologies, emphasizing the need for moral and ethical perspectives. To foster moral behavior and responsible action, including ethical values in IT systems and processes can be a solid option. By incorporating a socio-technical perspective, we are able to analyze the various aspects of BPM and organizational processes and the incorporated values. We find an overall acknowledgment of the importance of values and ethics in BPM.

Design/methodology/approach

This publication explores ethical values within BPM through a systematic literature review (SLR). The study aims to identify the ethical dimensions inherent in BPM and their practical implications in process management and task execution. The methodological approach adopted is a SLR (Boell and Cecez-Kecmanovic, 2015), adapting the PRISMA guidelines (Page et al., 2021) to identify 82 articles from 21 top IS journals suggested by Lowry et al. (2013).

Findings

A descriptive framework is developed to explain the use and application of ethical values within business processes. This framework enables practitioners and researchers to categorize and understand the various ethical considerations involved in BPM. It provides a structured approach highlighting the interrelation between process perspectives and ethical values, demonstrating how different BPM approaches may have varying ethical implications. We compare past and future research in business processes, identifying areas for further investigation and theoretical development. A historical analysis of values and literature also helps contextualize contemporary discussions on ethics in BPM, shedding light on the evolution of ethical considerations within this domain.

Originality/value

Our study contributes to a more nuanced understanding of BPM, highlighting the importance of considering ethical values and socio-technical perspectives in designing and implementing business processes. These findings contribute to understanding the values associated with different types of processes and their employment and highlight potential areas for future research. Our study provides ethics-oriented research in IS with novel insights by examining BPM from an ethical value perspective. We contribute to the BPM literature by examining which values are applied in which process types from which perspective. In addition, our research suggestions provide food for thought for both research streams.