bluuebunny/crossref_metadata_2025 huggingface dataset:
The circulating cell-free DNA landscape in sepsis is dominated by impaired liver clearance
Authors: Cano-Gamez Kiki , Maclean Patrick , Inoue Masato , Hussainy Sakineh , Foss Elisabeth , Wainwright Chloe , Qin Hanyu , McKechnie Stuart , Song Chun-Xiao , Knight Julian C.
Published: February 2025

Circulating cell-free DNA (cfDNA) is a promising molecular biomarker. However, its utility in severe infection remains poorly understood. Here, we isolated cfDNA from sepsis patients and controls, demonstrating a 41-fold increase in the amount of cfDNA in circulation during disease. We used sequencing to reconstruct cfDNA methylomes, fragmentation profiles, and nucleosome footprints across 56 samples. We observed no difference in cfDNA composition between patients and controls, challenging the idea that cfDNA increases due to higher immune cell death during sepsis. Instead, we suggest that liver dysfunction prevents efficient clearance of cfDNA during disease. This was supported by fragmentation and end-motif patterns, both of which showed evidence of cfDNA being exposed to circulating nucleases for a prolonged period, proportionally to the extent of liver dysfunction. Variation in cfDNA of megakaryocyte-erythroid progenitor origin was also a significant contributor in sepsis, increasing over time. Moreover, we showed that cfDNA retains nucleosome footprints with cell type-specific gene activity information. We developed a novel approach to study nucleosome phasing that successfully recovers tissue-specific signatures. By combining this with single-cell data, we demonstrated that sepsis patients with liver dysfunction have higher amounts of cfDNA derived from Kupffer cells and the liver parenchyma. In conclusion, we present the first high-throughput multi-modal study of cfDNA during sepsis, which will serve as a reference point for future studies on the role of this biomarker in critical illness.
Understanding the Bidirectional Relationship Between Chronic Respiratory Disease and Cardiovascular Disease Using Genetic Evidence
Authors: Naesilla  , Quint Jennifer , Zuber Verena
Published: February 2025

Background

Chronic respiratory diseases (CRD) and cardiovascular diseases (CVD) are leading global health burdens. Despite being common, CRD and CVD comorbidity is often underestimated due to overlapping symptoms and risk factors. Consequently, their relationship remains unclear.

Aims and Objectives

To determine the bidirectional genetic relationship between CRD and CVD and explore smoking and inflammation as potentially shared joint risk factors.

Methods

We conducted bidirectional Mendelian randomization (MR) to explore CRD-CVD relationships. Summary statistics from genome-wide association studies were retrieved for COPD, asthma, coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and ischemic stroke (IS). We performed additional analysis including univariable MR for smoking, multivariable MR adjusting for smoking, and cis-MR to investigate the role of inflammatory markers.

Results

Our MR analysis found limited genetic evidence of relationships between CRD toward CVD, and vice versa. However, a nominally significant genetic association was observed between asthma and an increased risk of AF (ORIVW1.036, 95% CI: 1.003-1.070), remaining weakly significant after adjusting for smoking (ORIVW1.040, 95%CI 1.008 – 1.074). Genetically predicted lifetime smoking strongly increased all CRD and CVD risk. Additionally, genetically proxied IL6R concentration associated with increased asthma risk and decreased CAD, MI, AF, and IS risk, while IL1RN decreased COPD risk but increased CAD and MI risk.

Conclusion

While we found limited genetic evidence linking CRD and CVD, smoking and inflammatory markers commonly affect both. These findings highlight the complexity of CRD-CVD comorbidities, whose pathophysiology likely does not involve direct causation of each other.
Post Stroke Cognitive Impairment: more than a lesion-symptom model
Authors: Huygelier Hanne , Moore Margaret Jane , Odom Annick , Tuts Nora , Thielen Hella , Mancuso Mauro , Gillebert Céline R. , Demeyere Nele
Published: February 2025

Post-stroke cognitive impairment (PSCI) is highly heterogeneous, reflecting both domain-specific deficits associated with focal lesions and broader impairments linked to premorbid health and demographic factors. In the current study we investigated whether PSCI can be distinguished into distinct across-domain cognitive profiles and how such PSCI profiles are associated with lesion neuroanatomy, demographic and premorbid health factors.

This cross-sectional study employed data-driven analyses (i.e., Latent Class Analysis) on 2172 stroke survivors who completed a domain-specific cognitive screen (i.e., Oxford Cognitive Screen) within 6 months after stroke (M = 19; Mdn = 7, SD = 35.7 days). In addition, the association of the PSCI profiles with lesion and demographic characteristics was investigated.

We identified two viable cognitive class solutions: a 5-class model capturing classical and novel PSCI profiles and a more detailed 13-class model reflecting a broader set of distinct cognitive profiles that commonly occur after stroke. The 5-class solution distinguished classical lateralized deficits (e.g., aphasia, neglect) alongside a minimal impairment and non-lateralized global impairment profile. In contrast, the 13-class solution provided finer-grained differentiation, particularly for non-lateralized cognitive profiles which were more strongly associated with premorbid health and education level. Importantly, lesion anatomy alone could not fully account for class distinctions. While lesion location was predictive, particularly, in hyper-acute stages, profiles for patients tested 2 weeks post-stroke revealed less influence of lesion location and more of lesion volume.

These findings underscore the importance of considering both anatomical and premorbid factors in understanding PSCI. By providing a nuanced classification of PSCI profiles, this study establishes a foundation for future translational research aimed at improving clinical care and predicting cognitive trajectories.
Differential expression patterns of sIgA in Human Breast milk (HBM) is dependent on birth outcome
Authors: Nye Gareth A , Rzepecka Magdalena J , Jones Christopher E , Harrison Kate
Published: February 2025

Breast milk is key for the development of newborns, particularly their immune systems and gut microbiota. In times of neonatal care, newborns are often supplemented with donor breast milk for a range of practical and medical reasons. However, we do not currently understand whether specific breast milk samples may be better suited at boosting the immune system. One of the most influential immune components is sIgA immunoglobulin.

Methods

Donor human breast milk samples provided by the North West Human Milk Bank were analysed for levels of sIgA using Abnova sIgA (Human) ELISA Kit according to the manufacturer’s instructions and analysed via statistical software packages based on the anonymised maternal characteristics.

Results

sIgA levels were significantly increased in breast milk samples following preterm and stillbirth outcomes compared with term and live deliveries. In preterm deliveries, sIgA levels remained significantly higher in breast milk for a longer postnatal period when compared with term deliveries. There was no significant changes in sIgA levels with antibiotic use.

Conclusion

The results presented in this study suggest that human breast milk is tailored to the baby from an immunological perspective. Higher levels of sIgA in breast milk being seen in pregnancies which did not end in a healthy baby i.e. pregnancies ending in preterm delivery or stillbirth would suggest there is an internal mechanism within the mother to provide additional support to a baby which is failing to grow successfully. This may open up new avenues to select donor samples specifically to assist in babies which are born premature to improve their immune systems.

Key Messages

Research has long shown that human breast milk is best for the development of newborn immune systems and gut microbiota

In neonatal settings, donor breast milk is used to supplement in times of need

This study shows for the first time that immunological factors can be altered based on fetal outcome measures

This may inform the provision of donor breast milk in neonatal feeding to ensure maximum immune development in preterm babies.
The Black community’s perspectives on the Black maternal health crisis
Authors: Felix Kaytura , Mawuli Jay , McGhee Alejandro , Paloma Marjorie , Pollack Porter Keshia
Published: February 2025

Many Black people in the United States have responded to their excessively high risk for maternal mortality and morbidity by moving childbirth from hospital settings to community homes and birth centers. Black perinatal health leaders are increasingly advocating for investments in community strategies such as birth centers and community midwifery. Despite the excess burden of death and disease carried by that community, few studies have sought to investigate community solutions. This qualitative study was conducted between January and October of 2023 to explore how the Black community was responding to the maternal health crisis. It consisted of structured and unstructured conversations with fifty-seven experts, leaders, artists, and practitioners who were deeply knowledgeable about community approaches and an observation of one Black midwife caring for two Black postpartum clients in their homes. Participants perceived that the overemphasis on the negative mortality and morbidity statistics on Black birthing people in the media, without a concomitant attention to the solutions, is harmful to that community and discourages childbearing. They described significant yet often ignored positive contributions of Black women and identified Black community midwifery as an important yet under-resourced strategy. Direct observation of community midwifery care illustrated dominant themes of spirituality, support, and rest. These findings suggest that Black community midwifery is an important model of care that offers protective factors during the times that Black birthing people —postpartum—are most vulnerable to death and disease and warrant further investments and study.
Plasmodium falciparumgenomic surveillance reveals a diversity ofkelch13mutations in Zambia
Authors: Aranda-Díaz Andrés , Mwanza Sydney , Makhanthisa Takalani I. , Lauterbach Sonja B. , De Amaral Faith , Chisenga Mukosha , Mangena Brighton , Routledge Isobel , Letinić Blaženka , Kasonde Bertha , Chongwe Gershom , Mwenda Mulenga C. , Miller John M. , Hibwato Tricia , Jacob Chirwa , Hamainza Busiku , Bwalya Stephen , Chiwaula Japhet , Matoba Japhet , Sikaala Chadwick , Chimumbwa John , Wesolowski Amy , Smith Jennifer L. , Raman Jaishree , Hawela Moonga
Published: February 2025

Antimalarials are central to Zambia’s strategies for malaria control and elimination. Antimalarial drug resistance poses a significant threat to the effectiveness of artemisinin-based combination therapies and preventive strategies such as sulfadoxine-pyrimethamine chemoprevention in pregnant women. In this genomic surveillance study, dried blood spots and epidemiological data were collected from confirmed Plasmodium falciparum cases at 61 health facilities across all 10 Zambian provinces from March to July 2023. A total of 2,486 samples were genotyped using multiplexed amplicon sequencing to identify mutations in 12 genes associated with resistance to seven antimalarial drugs. Several mutations potentially associated with artemisinin partial resistance were identified, including the validated k13 P574L marker (0.66% adjusted national prevalence) and the candidate k13 P441L marker (1.39%). The distribution of mutations was heterogeneous, with many health facilities reporting resistance markers in more than 5% of infections, and in some instances, up to 46%. The mdr1 N86 genotype, associated with decreased lumefantrine susceptibility, was found in all samples. Very high levels of sulfadoxine-pyrimethamine resistance markers were observed, including dhps K540E (93.26%). The variable prevalence of resistance markers underscores the need for routine molecular surveillance to detect emergent resistance and guide malaria control strategies. These results also call for studies to understand the clinical implications of these mutations and ensure the continued efficacy of antimalarial interventions in Zambia.
Time-series modeling of epidemics in complex populations: detecting changes in incidence volatility over time
Authors: Aber Rachael , Di Yanming , Dalziel Benjamin D.
Published: February 2025

Trends in infectious disease incidence provide important information about epidemic dynamics and prospects for control. Higher-frequency variation around incidence trends can shed light on the processes driving epidemics in complex populations, as transmission heterogeneity, shifting landscapes of susceptibility, and fluctuations in reporting can impact the volatility of observed case counts. However, measures of temporal volatility in incidence, and how volatility changes over time, are often overlooked in population-level analyses of incidence data, which typically focus on moving averages. Here we present a statistical framework to quantify temporal changes in incidence dispersion and detect rapid shifts in the dispersion parameter, which may signal new epidemic phases. We apply the method to COVID-19 incidence data in 144 United States (US) counties from the January 1st, 2020 to March 23rd, 2023. Theory predicts that dispersion should be inversely proportional to incidence, however our method reveals pronounced temporal trends in dispersion that are not explained by incidence alone, but which are replicated across counties. In particular, dispersion increased around the major surge in cases in 2022, and highly overdispersed patterns became more frequent later in the time series. These findings suggest that heterogeneity in transmission, susceptibility, and reporting could play important roles in driving large surges and extending epidemic duration. The dispersion of incidence time series can contain structured information which enhances predictive understanding of the underlying drivers of transmission, with potential applications as leading indicators for public health response.

Author summary

Understanding patterns in infectious disease incidence is crucial for understanding epidemic dynamics and for developing effective public health policy. Traditional metrics used to quantify incidence patterns often overlook variability as an important characteristic of incidence time series. Quantifying variability around incidence trends can elucidate important underlying processes, including transmission heterogeneity. We developed a statistical framework to quantify temporal changes in case count dispersion within a single time series and applied the method to COVID-19 case count data. We found that conspicuous shifts in dispersion occurred across counties concurrently, and that these shifts were not explained by incidence alone. Dispersion increased around peaks in incidence such as the major surge in cases in 2022, and dispersion also increased as the pandemic progressed. These increases potentially indicate transmission heterogeneity, changes in the susceptibility landscape, or that there were changes in reporting. Shifts in dispersion can also indicate shifts in epidemic phase, so our method provides a way for public health officials to anticipate and manage changes in epidemic regime and the drivers of transmission.
Neurochemical markers of uncertainty processing in humans
Authors: Jassim Nazia , Waade Peter Thestrup , Parsons Owen , Petzschner Frederike H , Rua Caterina , Rodgers Christopher T , Baron-Cohen Simon , Suckling John , Mathys Christoph , Lawson Rebecca P
Published: February 2025

How individuals process and respond to uncertainty has important implications for cognition and mental health. Here we use computational phenotyping to examine individualised “uncertainty fingerprints” in relation to neurometabolites and trait anxiety in humans. We introduce a novel categorical state-transition extension of the Hierarchical Gaussian Filter (HGF) to capture implicit learning in a four-choice probabilistic sensorimotor reversal learning task by tracking beliefs about stimulus transitions. Using 7-Tesla Magnetic Resonance Spectroscopy, we measured baseline neurotransmitter levels in the primary motor cortex (M1). Model-based results revealed dynamic belief updating in response to environmental changes. We further found region-specific relationships between M1 glutamate+ glutamine levels and prediction errors and volatility beliefs, revealing an important neural marker of probabilistic reversal learning in humans. High trait anxiety was associated with faster post-reversal responses. By integrating computational modelling with neurochemical assessments, this study provides novel insights into the neurocomputations that drive individual differences in processing uncertainty.
A multiomic network approach uncovers disease modifying mechanisms of inborn errors of metabolism
Authors: Bender Aaron , Ranea-Robles Pablo , Williams Evan , Mirzaian Mina , Heimel J. Alexander , Levelt Christiaan N , Wanders Ronald J.A. , Aerts Johannes M. , Zhu Jun , Auwerx Johan , Houten Sander M. , Argmann Carmen
Published: February 2025

For many inborn errors of metabolism (IEM) the understanding of disease mechanisms remains limited in part explaining their unmet medical needs. We hypothesize that the expressivity of IEM disease phenotypes is affected by the activity of specific modifier pathways, which is controlled by rare and common polygenic variation. To identify these modulating pathways, we used RNA sequencing to generate molecular signatures of IEM in disease relevant tissues. We then integrated these disease signatures with multiomic data and gene regulatory networks generated from animal and human populations without overt IEM. We identified and subsequently validated glucocorticoid signaling as a candidate modifier of mitochondrial fatty acid oxidation disorders, and we re-capitulated complement signaling as a modifier of inflammation in Gaucher disease. Our work describes a novel approach that can overcome the rare disease-rare data dilemma, and reveal new IEM pathophysiology and potential drug targets using multiomics data in seemingly healthy populations.
Glyco-STORM: Nanoscale Mapping of the Cellular Glycosylation Landscape
Authors: Schroeter Helene Gregoria , Sass Steffen , Heilemann Mike , Kuner Thomas , Klevanski Maja
Published: February 2025

Glycosylation is a crucial biochemical modification of proteins and other biomolecules in cells that generates an exceptional structural and functional diversity. Aberrant glycosylation is implicated in numerous diseases, including neurodegenerative disorders and cancer. Despite its significance, methodological constraints to date have limited the exploration of the nanometer scale spatial arrangement of glycans across entire cells. We developed Glyco-STORM, a super-resolution imaging approach that generates nano-structural maps of cellular glycosylation. Glyco-STORM employs fluorophore-labeled lectins and multiplexed single-molecule super-resolution microscopy, in combination with nanoscale spatial pattern analysis. For example, Glyco-STORM unraveled nanodomains within the endoplasmic reticulum, subdomains along the Golgi axes, and a polarized lysosomal clathrin coat. At synaptic contact sites, mature glycans delineate the synaptic cleft and subsynaptic tubules adjacent to the postsynaptic density. In summary, Glyco-STORM elucidates the spatial arrangement of glycosylation sites from subcellular to molecular levels, revealing the previously obscured glycosylation landscape at nanoscale and establishing a ’spatial glycosylation code’ that provides a unique perspective on cellular organization distinct from traditional protein-centric views.
A Single Mutation in TRPC6 Protects Mice from Acute Lung Injury by Regenerating Endothelium
Authors: Anwar Mumtaz , Balaji Raghunathrao Vijay Avin , Amin Ruhul , Vellingiri Vigneshwaran , Joshi Jagdish Chandra , Akhter Md Zahid , Tauseef Mohammad , El-Erian Ibrahim Hassan , Khaki Nazanin , Fancher Ibra S. , Abdelkarim Hazem , Levitan Irena , Chronis Konstantinos , Gaponenko Vadim , Mehta Dolly
Published: February 2025

Regenerating vascular endothelium under sepsis, trauma, and viral infections is vital for promoting the resolution of inflammatory diseases such as acute lung injury (ALI). Transient receptor potential canonical (TRPC) channels mediated Ca2+entry compromises organ functions and survival from lung injury. Through decoding the domain in TRPC6 responsible for vascular injury, we unveiled the intricate molecular mechanisms underlying vascular regeneration in injured tissue. We found that the substitution of isoleucine111within the Istankyrin domain of TRPC6 for its isomer111leucine (I111L-TRPC6) altered channel localization at the membrane, blocked TRPC6-mediated Ca2+entry and cation currents without affecting TRPC6 protein expression. Next, we delivered WT-TRPC6 and I111L-TRPC6 to the endothelial cells (ECs) of TRPC6 knockout mice using liposomes and found that while WT-TRPC6 induced lung vascular inflammatory injury and EC death these responses were blocked in lungs expressing I111L-TRPC6 mutant. Instead, the I111L-TRPC6 mutant promoted lung EC proliferation and prevented vascular injury. These responses were recapitulated in a preclinical mouse model of ALI after injection of engineered TRPC6-blocking peptide, suggesting a novel strategy for regenerating anti-inflammatory vascular niche and preventing ALI therapeutically.
Synaptic vesicle glycoprotein 2 enables viable aneuploidy following centrosome amplification
Authors: Blackmer Jane E. , Jezuit Erin A. , Chakraborty Archan , Montague Ruth A. , Peterson Nora G. , Outlaw William , Fox Donald T.
Published: February 2025

Amplified centrosome number causes genomic instability, most severely through division into more than two aneuploid daughter cells (multipolar mitosis). Several mechanisms that suppress multipolar division have been uncovered, yet mechanisms that favor viable multipolar division are poorly understood. To uncover factors that promote viability in cells with frequent centrosome amplification and multipolar division, we conducted an unbiasedDrosophilagenetic screen. In 642 mutagenized lines, we exploited the ability of intestinal papillar cells to form and function despite multipolar divisions. Our top hit is an unnamed gene,CG3168. We name this genesynaptic vesicle glycoprotein 2, reflecting homology to human Synaptic Vesicle Glycoprotein 2 (SV2) proteins. GFP-tagged SV2 localizes to the plasma membrane. In cells with amplified centrosomes, SV2 positions membrane-adjacent centrosomes, which prevents severe errors in chromosome alignment and segregation. Our results uncover membrane-based multipolar division regulation and reveal a novel vulnerability in cells with common cancer properties.
Leveraging seasonal dynamics to identify the strength of disease transmission along multiple environmental pathways
Authors: Shioda Kayoko , Watanabe Miwa , Freeman Matthew , Levy Karen , Brouwer Andrew
Published: February 2025

Background

Many pathogens spread through multiple transmission pathways, making it difficult to identify the dominant transmission pathway for a given pathogen. Including a comprehensive set of relevant pathways in infectious disease transmission (IDT) models can provide insight into the contribution of each pathway to infections and allow for comparisons of the potential impact of control strategies targeting various pathways. Seasonal patterns in pathogen prevalence, combined with environmental testing, may allow us to differentiate the contributions of different pathways.

Methods

We conducted an identifiability analysis for an IDT model with three transmission pathways: direct person-to-person and two indirect, environmental pathways (water-to-person and food-to-person). We ran a series of simulations to understand the conditions under which we can successfully identify the dominant transmission pathway. Specifically, we explored the effects of different magnitudes of the transmission rate for each pathway and the seasonal timing of peak pathogen concentrations in water and food.

Results

Under the proposed data collection approach, we were able to successfully determine the dominant transmission pathway when simulated peak seasonality in water and food contamination differed by at least one month, even when the difference in the true transmission rates was small. However, we did not always correctly estimate the transmission rates used to generate the simulated data, even if we correctly determined the relative strengths of the pathways. When the simulated contamination in water and food peaked at the same time, the IDT model failed to determine the dominant pathway, regardless of the relative magnitudes of the true transmission rates.

Discussion

Our analysis found that IDT models can be a powerful tool to differentiate the contribution of different pathways to human infection with relevant empirical data on pathogen contamination in exposure sources. Our findings can help researchers design future studies and determine the feasibility of a study based on the seasonality in environmental samples if such data are available.
Associations of Anxiety, Depression, and Sleep Quality with MNBI, PSPW-I, and ECJ-CI in rGERD, FH, and RH Patients: A Retrospective Study
Authors: Lou Lunsheng , Huang Yurong , Yang Wangliu , Song Gengqing , Yang Jie
Published: February 2025

Objective

This study examined the impact of anxiety, depression, and sleep quality on mean nocturnal baseline impedance (MNBI), post-reflux swallow-induced peristaltic wave index (PSPW-I), and esophagogastric junction contractile index (EGJ- CI) in patients with refractory gastro-esophageal reflux disease (rGERD), functional heartburn (FH), and reflux hypersensitivity (RH).

Methods

Retrospective analysis included 75 patients aged 18-70 with persistent reflux symptoms despite 8 weeks of proton pump inhibitor (PPI) therapy. Evaluations included esophagogastroduodenoscopy, high-resolution manometry, 24-hour pH- impedance monitoring, and psychological assessments (SAS, SDS, PSQI). Patients were grouped into rGERD, FH, and RH. MNBI, PSPW-I, and EGJ-CI were compared, and correlations with psychological and sleep parameters were analyzed.

Results

Distal MNBI was significantly lower in rGERD (1177.91 ± 707.22 Ω) vs. FH (1995.77 ± 476.02 Ω) and RH (2062.35 ± 509.93 Ω) (P < 0.001). Anxiety prevalence was 85.7% in rGERD, 64.7% in FH, and 67.5% in RH (P = 0.302); depression affected 78.6% of rGERD, 70.8% of FH, and 72.9% of RH patients (P = 0.942). Poor sleep quality was present in >80% of all groups. PSPW-I negatively correlated with anxiety (r = −0.181, P < 0.05) and depression (r = −0.158, P < 0.05), as did proximal MNBI with depression (r = −0.175, P < 0.05). A distal MNBI cutoff of 1531 Ω distinguished rGERD from FH/RH with 71.4% sensitivity and 87.5% specificity (AUC = 0.80).

Conclusion

Anxiety, depression, and poor sleep quality impair PPI efficacy and worsen esophageal acid clearance. Distal MNBI effectively differentiates rGERD from FH/RH. Addressing psychological and sleep disturbances may improve treatment outcomes in refractory reflux patients.
Validity and wear compliance of wrist-wearable activity trackers in free-living schoolchildren: validation study
Authors: Yamakita Mitsuya , Ando Daisuke , Sato Miri , Akiyama Yuka , Yamaguchi Kaori , Yamagata Zentaro
Published: February 2025

Introduction

Wearable activity trackers are widely available for promoting physical activity (PA) and reducing sedentary behavior (SB). However, studies assessing their validity for PA and SB measurement in free-living conditions in school-age children remain limited.

Objective

This study aimed to evaluate the criterion validity and wear compliance of the Fitbit Ace, a wrist-worn wearable activity tracker designed for children, in measuring PA and SB under free-living conditions.

Methods

A total of 102 children (mean age: 10.2 years; 44.1% girls) simultaneously wore a waist-worn accelerometer (Omron Active Style Pro HJA-750c; ASP HJA-750c) and a Fitbit Ace for 11 consecutive days. Step count and time spent in SB, light PA (LPA), moderate PA (MPA), and vigorous PA (VPA) were collected from both devices. Pearson’s and Spearman’s correlations assessed criterion validity, while Bland–Altman plots, mean absolute percentage error (MAPE), and intraclass correlation coefficients were used to evaluate agreement. Wear compliance was compared between the two devices.

Results

The Fitbit Ace showed a very strong correlation with step count and strong correlations with SB, LPA, and moderate-to-vigorous PA (MVPA). However, significant differences were observed for all PA variables. The Fitbit Ace overestimated step count, SB, VPA, and MVPA, whereas it underestimated LPA and MPA. Agreement between devices was low, with proportional errors in step count, LPA, VPA, and MVPA. MAPE exceeded 20% for all variables, including step count (21.7%), SB (31.2%), LPA (30.3%), and MVPA (120.7%). The proportion of children meeting the criterion of ≥10 h/day wear criterion was higher for the Fitbit Ace (83.2%) than for the ASP HJA-750c (57.8%), as was adherence to ≥4 days (97.0% vs. 62.2%).

Conclusion

While caution is needed when using the Fitbit Ace for precise measurement of individual PA, it is a useful tool for assessing overall patterns of step count, SB, and LPA in school-aged children.
Estimating physical conditions supporting gradients of ATP concentration in the eukaryotic cell
Authors: Kumar Rajneesh , Johnston Iain G.
Published: February 2025

The ATP molecule serves as an energy currency in eukaryotes (and all life), providing the energy needed for many essential cellular processes. But the extent to which substantial spatial differences exist in ATP concentration in the cell remains incompletely known. It is variously argued that ATP diffuses too quickly for large gradients to be established, or that the high rates of ATP production and use (sources and sinks) can support large gradients even with rapid diffusion – and microscopic models and detailed experiments in different specific cases support both pictures. Here we attempt a mesoscopic investigation, using reaction-diffusion modelling in a simple biophysical picture of the cell to attempt to ask, generally, which conditions cause substantial ATP gradients to emerge within eukaryotic cells. If ATP sources (like mitochondria) or sinks (like the nucleus) are spatially clustered, large fold changes in concentration can exist across the cell; if sources and sinks are more spread then rapid diffusion indeed prevents large gradients being established. This dependence holds in model cells of different sizes, suggesting its generality across cell types. Our theoretical work will complement developing intracellular approaches exploring ATP concentration inside eukaryotic cells.
The genetic architecture of polygenic adaptation under a network-derived trait
Authors: O’Brien Nicholas L. V. , Holland Barbara , Engelstädter Jan , Ortiz-Barrientos Daniel
Published: February 2025

The genetic architecture of adaptation varies across species, populations, and traits. While existing models capture aspects like the number of loci, effect sizes, and allele frequencies, they often overlook the molecular processes underlying trait expression. We investigated how gene regulatory networks influence quantitative variation during adaptation by examining the negative autoregulation (NAR) motif in two configurations: K+, with four evolving network components, and K-, with two components. Using forward-time simulations, we tracked populations adapting to a shifted phenotypic optimum under varying genetic architectures. We found that K+ populations maintained rapid adaptation despite low recombination, preserving high genetic variance through positive epistasis and stronger linkage disequilibrium. Under low recombination, K+ populations reached the optimum through diverse molecular configurations, while responses were more uniform under high recombination. In contrast, K− and additive models showed impaired adaptation under low recombination. Our findings demonstrate that network structure fundamentally influences the distribution of variation within the molecular architecture of traits, with certain networks providing unexpected robustness against low recombination rates. This suggests that molecular complexity may confer evolutionary advantages in natural populations.
Isotropic, aberration-corrected light sheet microscopy for rapid high-resolution imaging of cleared tissue
Authors: Aakhte Mostafa , Müller Gesine F. , Li Joe , Weiss Kurt R. , Roos Lennart , Diniz Aleyna M. , Wenzel Jan , Schwaninger Markus , Moser Tobias , Huisken Jan
Published: February 2025

Light sheet microscopy is the ideal technique for multiscale imaging of large and cleared tissues, and it is desirable to achieve the highest possible isotropic resolution across the entire sample. However, isotropic resolution for a centimeter-sized sample has only been achieved with slow and often aberrated, axially scanned light sheets, resulting in a low resolution of several micrometers. Here, we introduce a compact, high-speed light sheet fluorescence microscope with isotropic sub-micron resolution optimized for cleared tissue. We introduce three major opto-mechanical innovations using off-the-shelf optics to achieve an isotropic resolution of 850 nm across samples up to 1 cm3and refractive indices ranging from 1.33 to 1.56. We show that combining an air objective and a meniscus lens achieves an axially swept light sheet with sub-micron diffraction-limited resolution, free of aberrations. The effective field of view is increased 2-fold by correcting the field curvature of the light sheet with a concave mirror in the remote focusing unit. Furthermore, the imaging speed is enhanced 10- fold by adapting the light sheet’s motion with a closed-loop feedback, reaching 100 frames per second while maintaining isotropic resolution across the large field of view. Finally, we showcase the performance of our light sheet system for imaging from subcellular up to centimeter scale in cleared mouse cochlea and brain.
Differential AXL expression and regulation of Arf1 controls matrix stiffness-dependent Golgi organization and function in breast cancer cells
Authors: Saha Arnav , Sherkhane Tushar , Balasubramanian Nagaraj
Published: February 2025

Integrin-mediated cell-matrix adhesion regulates cell growth and survival and is often deregulated in transformed cancer cells, promoting anchorage independence. Integrins are essential regulators of cellular mechanotransduction, known to be altered in cancer cells. In breast cancers, tumour stiffening is a well-characterized feature of the disease progression. The Golgi apparatus, regulated by integrin-mediated adhesion in responding to mechanosensory cues, could support cancer progression. MDAMB231 and MCF7 cells with distinct Golgi organization and altered mechanosensing were evaluated. In MDAMB231 cells the organized Golgi in stable adherent cells becomes disorganised on loss of adhesion. This contrasts with MCF7 cells, where the Golgi remains disorganized regardless of the adhesion status. In MDAMB231 cells, increasing matrix stiffness promotes Golgi organization and regulates Golgi-dependent microtubule acetylation. In MCF7 cells, the Golgi stays disorganised despite increasing stiffness. Both cell types show stiffness-dependent cell spreading, with MCF7 cells spreading more efficiently than MDAMB231 cells - a difference that may be partially mediated by their differential Golgi organization. AXL, a receptor tyrosine kinase, is known to be involved in rigidity sensing and is differentially expressed in MDAMB231 (high) vs MCF7 (no expression) cells. AXL inhibition (by R428) and siRNA-mediated AXL knockdown disrupt stiffness-dependent Golgi organization in MDAMB231 cells, promoting cell spreading. Transient and stable AXL expression in MCF7 cells causes the Golgi to become predominantly organised and respond to higher matrix stiffness, affecting cell spreading. Stiffness-dependent AXL expression supports stiffness-dependent Arf1 expression and activation to drive Golgi organization. Thus, matrix mechanosensing through the AXL-Arf1-Golgi pathway could regulate vital cellular processes in breast cancer cells.
Toward quantitative precision for QCD at large densities
Authors: Ihssen Friederike , Pawlowski Jan M. , Sattler Franz R. , Wink Nicolas
Published: February 2025

QCD at large density reveals a rich phase structure, ranging from a potential critical end point and inhomogeneous phases or moat regimes to color superconducting ones with competing order effects. Resolving this region in the phase diagram of QCD with functional approaches requires a great deal of quantitative reliability already for a qualitative access. In the present work, we systematically extend the functional renormalization group approach to low-energy QCD by setting up a fully self-consistent approximation scheme in a low-energy effective quark-meson theory. In this approximation, all pointlike multiscattering events of the mesonic pion and the σ mode are taken into account in terms of an effective potential as well as all higher quark-antiquark-mesonic scattering orders. As a first application we compute the phase structure of QCD including its low temperature, large chemical potential part. The quantitative reliability of the approximation and systematic extensions is also discussed.

Published by the American Physical Society
2025
Unsupervised learning approach for benchmark models to identify construction projects with high accident risk levels
Authors: Mun Hyeongjun , Jeong Jaewook , Jeong Jaemin , Kumi Louis
Published: February 2025

Purpose

The construction sector is highly prone to accidents, traditionally assessed using subjective qualitative measurements. To enhance the allocation of risk management resources and identify high-risk projects during pre-construction, an objective and quantitative approach is necessary. This study introduces a three-step clustering methodology to quantitatively evaluate accident risk levels in construction projects.

Design/methodology/approach

In the first step, accident and total construction revenue by project were collected to calculate accident probabilities. In the second step, accident probabilities were calculated by project type using the data collected in the first step. After that, benchmark models were suggested using clustering methods to identify high-risk project types for risk management. Before suggesting the benchmark models, an uncertainty analysis was conducted due to the limited amount of data. In the third step, the suggested benchmark models were validated for accuracy.

Findings

The results categorized risk levels for fatalities and injuries into four distinct groups. Validation through ordinal logistic regression demonstrated high explanatory power, with fatality risk levels ranging from 79.9 to 100% and injury risk levels from 90.3 to 100%.

Originality/value

This benchmark model facilitates effective comparisons and analyses across various construction sectors and countries, offering a robust quantitative standard for risk management. By identifying high-risk projects such as “Dam,” this methodology enables better resource allocation during the pre-construction phase, thereby improving overall safety management in the construction industry and providing a basis for legislative applications.
“Green university initiatives and environmental self-identity: waste sorting in Baltic higher education”
Authors: Rūtelionė Aušra , Bhutto Muhammad Yaseen , Miceikienė Astrida
Published: February 2025

Purpose

This paper aims to examine the waste sorting practices of Lithuanian students and integrate the influence of green university initiatives (GUIs) and environmental self-identity (ESI) into the theoretical framework of the theory of planned behavior (TPB). Furthermore, it examines the potential impact of gender on waste-sorting behavior.

Design/methodology/approach

Data were collected from 255 Lithuanian students using a standardized questionnaire. Convergent and discriminant validity analyses were handled to ensure validity and reliability, and hypothetical relationships were evaluated using structural equation modeling.

Findings

This study confirms GUIs significantly encourage students’ ESI and positively influence their attitudes, subjective norms and perceived behavioral control in waste sorting. In addition, ESI also significantly affects attitude, subjective norms and perceived behavioral control. The study features gender differences, with female students showing stronger associations between GUIs and waste-sorting intentions, reflecting increased environmental awareness and social norms that encourage sustainable behavior. Although subjective norms did not significantly induce waste sorting intentions, the results highlight the essential role of ESI and GUIs in progressing university ecological practices.

Originality/value

This groundbreaking study combines GUIs, ESI and the TPB to examine students’ waste separation behavior. It fills the noticeable literature gap and provides new insights into how gender affects universities’ environmental practices. It suggests actionable strategies to promote sustainable campus cultures and gender-sensitive programs.
Real option valuation using Weibull distribution: a new framework for depreciation risk management
Authors: Ko Seok Bin
Published: February 2025

This study aims to develop an accurate option pricing model for car leases by introducing a put option valuation framework based on the Weibull distribution. Traditional models typically assume asset values follow a lognormal distribution, failing to capture the left-skewed nature and bounded dynamics. To address this limitation, this study compares the performance of the Weibull distribution with that of the lognormal model using residual value data from two popular car models in South Korea, evaluating each model’s ability to reflect unique depreciation patterns. The findings demonstrate that the Weibull distribution provides a superior fit to the data, leading to more precise option pricing. This enhanced accuracy is crucial for auto finance companies navigating uncertainties in used car prices, particularly as the mobility services and car leasing markets continue to expand. Moreover, the practical implications of this research extend beyond the auto finance industry; insights from this study can inform sectors dealing with skewed or bounded assets, such as insurance products and financial derivatives, thereby enabling improved risk assessment and decision-making processes. This research introduces a novel approach to modeling put option values using the Weibull distribution, filling a significant gap in the existing literature on car lease option pricing. However, as this is the first study to model put option values using the Weibull distribution, further research is necessary. Specifically, investigating volatility patterns over the lifecycle of used cars could significantly enhance the value of this framework.
Teaching controversial topics in the politically polarized suburbs
Authors: Waller Melanie
Published: February 2025

Purpose

The purpose of this qualitative study is to explore how high school social studies teachers perceive and address controversial topics in politically polarized suburban classrooms. Research indicates that political polarization significantly affects both teachers and students, with suburban communities being some of the most politically divided in the U.S. By examining the experiences of teachers in these suburban settings and their approaches to handling controversial topics, this study aims to shed light on how the political climate influences teaching practices, discussions of controversial issues and teachers' curriculum-related decisions.

Design/methodology/approach

This is a qualitative research study. I interviewed six suburban Long Island high school social studies teachers over the 2021–2022 school year. Each teacher was interviewed twice, with interviews ranging from one to two hours. The interviews were semi-structured and asked the teachers about the purposes of teaching social studies, their communities, their experiences teaching controversial political topics, obstacles around teaching controversial political topics and the ways in which their communities received the teaching of controversial political topics. I used thematic analysis to analyze the interviews. Each interview was analyzed inductively and deductively and coded over three iterative cycles.

Findings

These “controversial” topics come with both explicit and implicit pressure to avoid discussion and deliberation in the classroom. The first finding in this section centers on explicit and implicit pressure on teachers to avoid controversial topics. The second finding highlights the consequences of that pressure on teacher curricular decision making. The third and fourth findings are focused on participants' responses to explicit and implicit pressures to avoid controversial topics. The third finding articulates on the role of tenure in approaching controversial topics in polarized communities. The final finding defines and explores teacher use of political opaqueness.

Originality/value

This work adds to the existing literature on social studies education by providing an analysis of how controversial topics are understood and enacted in the suburban environment. By adding the specificity of context to my research I examine the ways in which controversial topics are defined part by their environment, and teacher interpretation of that environment. Further, this work adds to the literature on deliberative pedagogies and controversial topics by considering the roles that contemporary local and national politics play in enacting controversial topics, and the consequences on the classroom and teaching.
The Moderating Role of Societal Cultural Values and Practices on the Relationship Between Workplace Aggression and Employee Engagement
Authors: Rafferty Anthony
Published: February 2025

This article investigates the relationship between societal culture, the self‐reported incidence of workplace aggression and its effects on employee engagement. While justice‐based accounts emphasise the role of cultural values and attributional models focus on cultural practices, the Focus Theory of Normative Conduct is applied to understand how both cultural values and practices may influence employee outcomes. Utilising the GLOBE survey measures, a nationally representative study of 20 countries was conducted. Results indicate that higher levels of power distance, assertiveness, institutional collectivism, and in‐group collectivism—in terms of both values and practices—are associated with lower self‐reported workplace aggression. Moderation analyses revealed a greater negative effect of aggression on employee engagement in societies scoring higher on power distance or assertiveness values and practices and in‐group collectivism practices, while such effects were lower in countries with higher institutional collectivist practices or in‐group collectivist values. Implications for cross‐cultural human resource management and workplace interventions are discussed.